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Polyunsaturated Fatty Acids (PUFAs) References
(644 References)

Kainz, M., M. T. Arts et al. (2004). ” Essential fatty acids in the planktonic food web and their ecological role for higher trophic levels”. Limnol Oceanogr 49(5): 1784-1793.

Concentrations of essential fatty acids (EFAs) were measured in four size categories of planktonic organisms; seston (10–64 μm), microzooplankton (100–200 μm), mesozooplankton (200–500 μm), and macrozooplankton (>500 μm)—and in rainbow trout (Oncorhynchus mykiss) in coastal lakes. Size-dependent patterns in concentrations of specific fatty acids (FAs) are important for ecosystem function, because planktivorous fish and some invertebrates are size-selective predators. The retention of individual FAs differed among the four size categories of planktonic organisms in the study systems. Changes in individual EFA concentrations within the planktonic food web were similar in all coastal lakes sampled, which indicates the generality of the findings. Although concentrations of arachidonic acid, eicosapentaenoic acid (EPA), and linoleic acid increased steadily with plankton size, the concentration of a-linolenic acid decreased slightly in larger size fractions of zooplankton. Concentrations of another EFA, docosahexaenoic acid (DHA), declined sharply from mesozooplankton to the cladoceran-dominated macrozooplankton size class. The results indicate that the retention of EFAs, as a function of plankton size, is related, in part, to the taxonomic composition of planktonic food webs. The suggestion is that, in general, zooplankton exhibit an EPA-retentive metabolism with increasing body size, whereas different taxonomic groups within the planktonic food web retain DHA differently. Finally, it is concluded that EPA is highly retained in zooplankton, whereas in rainbow trout DHA is highly retained.


Yazdani, M., K. Ide, et al. (2004). "Effects of Caffeine on the Saturated and Monounsaturated Fatty Acids of the Newborn Rat Cerebellum." Ann Nutr Metab 48(2): 79-83.

            Caffeine (1,3,7-trimethylxanthine) is one of the most commonly consumed drugs in our daily life, and its use is increasing. However, very little attention has been paid to its potential effects on early growth and development. Because of the steady increase in breast feeding of infants and because caffeine diffuses readily into breast milk, the present study examined if caffeine intake by newborn rats during lactation would affect the saturated and monounsaturated fatty acids in the growing cerebellum. A total of 10 timed pregnant rats were purchased from the breeder. At birth litters were combined, and 8 pups were randomly assigned to each dam without regard to the sex of the pups. Dams with litters were divided into 2 groups. Dams of group 1 received a 20% protein diet as a control, and dams of group 2 received a 20% protein diet plus caffeine (4 mg/100 g BW). Pups were killed at day 10. The cerebellums were removed, weighed and homogenized. Gas chromatograph-mass spectrometry was used to identify and quantify free fatty acids. Chronic caffeine exposure from birth to day 10 in pups through the maternal milk resulted in a decrease in cerebellum weight, a significant increase in the saturated fatty acids, and a tendency toward an increase of monounsaturated fatty acids. In addition, there was a slight increase of some of the polyunsaturated fatty acids. However, there was no difference in food intake of the lactating dams and weight gain of the pups between the groups. These data indicate that early caffeine intake by the suckling pups alters the composition of fatty acids of the cerebellum; thus, avoidance of caffeine during lactation is critical. The risks and benefits of caffeine administration in premature infants must be carefully evaluated during this rapid period of brain growth. Copyright 2004 S. Karger AG, Basel


Yamada, S., T. Funada, et al. (2004). "Protein-bound 4-hydroxy-2-hexenal as a marker of oxidized n-3 polyunsaturated fatty acids." J Lipid Res.

            In the present study, to investigate the contribution of n-3 polyunsaturated fatty acids (n-3 PUFAs) in the oxidative modification of protein in vivo, we characterize the covalent binding of 4-hydroxy-2-hexenal (HHE), a potent cytotoxic aldehyde originating from the peroxidation of n-3 PUFAs, to protein and describe the production of this aldehyde in oxidatively modified LDL and in human atherosclerotic lesions. Upon incubation with bovine serum albumin, HHE was rapidly incorporated into the protein and generated the protein-linked carbonyl derivative, a potential marker of oxidatively modified proteins under oxidative stress. To detect the protein-bound HHE in vivo, we raised a monoclonal antibody HHE53 (mAb HHE53) directed to the HHE-modified protein and identified the Michael addition-type HHE-histidine adduct as the major epitope. This antibody reacted with copper-oxidized LDL, suggesting that HHE was produced during the oxidative modification of LDL. In addition, we demonstrated that the materials immunoreactive to mAb HHE53 indeed constituted the atherosclerotic lesions, in which intense positivity was associated primarily with macrophage-derived foam cells. The results of this study suggest that the reaction between oxidized n-3 PUFAs and protein might represent a process common to the formation of degenerative proteins during aging and its related diseases.


Tocher, D. R., J. Fonseca-Madrigal, et al. (2004). "Effects of water temperature and diets containing palm oil on fatty acid desaturation and oxidation in hepatocytes and intestinal enterocytes of rainbow trout (Oncorhynchus mykiss)." Comp Biochem Physiol B Biochem Mol Biol 137(1): 49-63.

            Food grade fisheries have reached their sustainable limits while aquaculture production has increased to meet consumer demands. However, for growth in aquaculture to continue and utilise sustainable, feeding ingredients, alternatives to fish oil (FO), the predominant lipid component of fish diets, must be developed. Therefore, there is currently considerable interest in the regulation of fatty acid metabolism in fish in order to determine strategies for the best use of plant oils in diets for commercially important cultured fish species. Plant oils are characteristically rich in C(18) polyunsaturated fatty acids (PUFA) but devoid of C(20) and C(22) highly unsaturated fatty acids (HUFA) found in FO. The fatty acyl desaturase enzyme activities involved in the biosynthesis of HUFA from PUFA are known to be under nutritional regulation and can be increased in fish fed diets rich in plant oils. However, fatty acid desaturase activity is also known to be modulated by water temperature in fish. The present study aimed to investigate the interaction between water temperature and diet in the regulation of fatty acid metabolism in rainbow trout. Trout, acclimatized to 7, 11 or 15 degrees C, were fed for 4 weeks on diets in which the FO was replaced in a graded manner by palm oil. At the end of the trial, fatty acyl desaturation/elongation and beta-oxidation activities were determined in isolated hepatocytes and intestinal enterocytes using [1-(14)C]18:3n-3 as substrate, and samples of liver were collected for analysis of lipid and fatty acid composition. The most obvious effect of temperature was that fatty acid desaturation/elongation and beta-oxidation were reduced in both hepatocytes and intestinal enterocytes from fish maintained at the highest water temperature (15 degrees C). There were differences between the two tissues with the highest desaturation/elongation and beta-oxidation activities tending to be in fish held at 11 degrees C in the case of hepatocytes, but 7 degrees C in enterocytes. Correlations between fatty acid metabolism and dietary palm oil were most clearly observed in desaturation/elongation activities in both hepatocytes and enterocytes at 11 degrees C. The highest beta-oxidation activities were generally observed in fish fed FO alone in both hepatocytes and enterocytes with palm oil having differential effects in the two cell types.


Skeaff, C. M., K. Williscroft, et al. (2004). "Replacing cows' with sheep's dairy fat lowers plasma cholesterol concentration in participants consuming dairy fat-rich diets." Eur J Clin Nutr 58(2): 250-7.

            OBJECTIVE:: To determine the effects on plasma cholesterol concentration of replacing cows' dairy fat with sheep's dairy fat. DESIGN:: Randomised crossover dietary intervention. SETTING:: General community, Dunedin, New Zealand. SUBJECTS:: Volunteer sample of 41 healthy adults with initial plasma cholesterol concentration between 4.8 and 7.8 mmol/l. INTERVENTIONS:: Participants were asked to follow a self-selected low-fat background diet throughout the study to which, during each of the 2, 3-week dairy diets, they were asked to add sheep's or cows' dairy products. MAIN OUTCOME MEASURES:: Energy and nutrient intakes, plasma triacylglycerol fatty acids, and plasma cholesterol. RESULTS:: Energy and nutrient intakes on the sheep-dairy and cow-dairy diets were very similar, with total, saturated, monounsaturated and polyunsaturated fat contributing 34, 18-19, 9, and 3% of total energy intake, respectively. Participants consumed approximately 50 g/day of dairy fat on each diet. Replacing cows' with sheep's dairy fat led to a 0.33 (0.11-0.56, 95% CI) mmol/l decrease (6%) in plasma total cholesterol concentration, from 5.53 (0.90, s.d.) to 5.20 (0.90) mmol/l. Plasma low-density lipoprotein (LDL) cholesterol was 0.18 (0.02-0.33) mmol/l lower on the sheep-dairy diet as was the concentration of plasma high-density lipoprotein (HDL) cholesterol, 0.11 (0.02-0.20) mmol/l. The LDL to HDL cholesterol ratio at the end of the sheep-dairy diet, 2.91 (1.10), was not significantly different (P>0.05) from the cow-dairy diet, 2.73 (0.83). CONCLUSIONS:: Within the context of a diet high in dairy fat (50 g/day), replacing cows' milk fat with sheep's milk fat leads to a small reduction in plasma cholesterol concentration, but no change in the ratio of LDL to HDL cholesterol. SPONSORSHIP:: Foundation for Research Science and Technology, New Zealand Government; Frontiers Group Company Limited.European Journal of Clinical Nutrition (2004) 58, 250-257. doi:10.1038/sj.ejcn.1601774


Sayanova, O. V. and J. A. Napier (2004). "Eicosapentaenoic acid: biosynthetic routes and the potential for synthesis in transgenic plants." Phytochemistry 65(2): 147-58.

            Long chain polyunsaturated fatty acids are now known to play important roles in human health. In particular, eicosapentaenoic acid (20:5Delta(5,8,11,14,17); n-3: EPA) is implicated as a protective agent in a range of pathologies such as cardiovascular disease and Metabolic Syndrome (Syndrome X). Eicosapentaenoic acid is currently sourced from fish oils, the presence of this fatty acid being due to the dietary piscine consumption of EPA-synthesising micro-algae. The biosynthetic pathway of EPA has been elucidated, and contains several alternative metabolic routes. Progress in using "reverse engineering" to transgenically mobilize the trait(s) for EPA are considered. In particular, the prospect of producing this important polyunsaturated fatty acid in transgenic oilseeds is highlighted, as is the urgent need for a sustainable replacement for diminishing fish stocks.


Sarkadi-Nagy, E., V. Wijendran, et al. (2004). "Formula feeding potentiates docosahexaenoic and arachidonic acid biosynthesis in term and preterm baboon neonates." J Lipid Res 45(1): 71-80.

            Infant formulas supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA) are now available in the United States; however, little is known about the factors that affect biosynthesis. Baboon neonates were assigned to one of four treatments: term, breast-fed; term, formula-fed; preterm (155 of 182 days gestation), formula-fed; and preterm, formula+DHA/ARA-fed. Standard formula had no DHA/ARA; supplemented formula had 0.61%wt DHA (0.3% of calories) and 1.21%wt ARA (0.6% of calories), and baboon breast milk contained 0.68 +/- 0.22%wt DHA and 0.62 +/- 0.12%wt ARA. At 14 days adjusted age, neonates received a combined oral dose of [U-(13)C]alpha-linolenic acid (LNA*) and [U-(13)C]linoleic acid (LA*), and tissues were analyzed 14 days after dose. Brain accretion of linolenic acid-derived DHA was approximately 3-fold greater for the formula groups than for the breast-fed group, and dietary DHA partially attenuated excess DHA synthesis among preterms. A similar, significant pattern was found in other organs. Brain linoleic acid-derived ARA accretion was significantly greater in the unsupplemented term group but not in the preterm groups compared with the breast-fed group. These data show that formula potentiates the biosynthesis/accretion of DHA/ARA in term and preterm neonates compared with breast-fed neonates and that the inclusion of DHA/ARA in preterm formula partially restores DHA/ARA biosynthesis to lower, breast-fed levels. Current formula DHA concentrations are inadequate to normalize long-chain polyunsaturated fatty acids synthesis to that of breast-fed levels.


Rasanen, M., S. Keskinen, et al. (2004). "Impact of nutrition counselling on nutrition knowledge and nutrient intake of 7- to 9-y-old children in an atherosclerosis prevention project." Eur J Clin Nutr 58(1): 162-72.

            OBJECTIVE:: To assess the impact of nutrition counselling given to 7.5- to 9-y-old children and their parents on children's nutrition knowledge and nutrient intakes. DESIGN AND SUBJECTS:: The study children are participants in a prospective, randomised STRIP study (Special Turku Coronary Risk Factor Intervention Project for Children), whose aim was to decrease the intakes of saturated fat and cholesterol while increasing the intake of unsaturated fat in the intervention children from the age of 7 months onwards. Nutrition counselling was given only to the parents until the child's age of 7 y. Nutrition knowledge and nutrient intakes (total energy, total fat, saturated fat, unsaturated fat and sodium) were studied in a time-restricted cohort of 47, 7-y-old intervention and 51 control children. Thereafter, nutrition counselling was given both to the children and parents. Children's nutrition knowledge and nutrient intakes were measured again at the age of 9 y. RESULTS:: Biannual nutrition counselling given to the intervention children and the parents maintained the differences in saturated fatty acid intake attained during the intervention given to the parents alone (11.5 vs 13.3 E% (percent of energy intake), at the age of 7 y, P<0.01; 11.1 vs 13.4 E% at the age of 9 y, respectively; P<0.01). The intervention children used more polyunsaturated fatty acids at the age of 9 y than the control children (5.7 vs 5.1 E%, P=0.05). At 7 y, the intervention and control children had similar nutrition knowledge scores (total knowledge score 12.9 vs 12.0, respectively, P=0.13). After 1.5 y of nutrition intervention, at 9 y, the intervention children's nutrition knowledge was higher than that of the controls (total nutrition score 16.5 vs 13.2, respectively, P<0.001) and the ability to explain the reasons for their picture choices in the nutrition knowledge test had increased. CONCLUSION:: This study showed that only a relatively short period of counselling with low input is needed to increase in children's nutrition knowledge and ability to explain nutrition-related subjects if advice has first been given to the parents and if the parents have received reinforcement and concrete help with parent-child communication after their children have been involved in the counselling. The differences attained in nutrient intake could also be maintained.European Journal of Clinical Nutrition (2004) 58, 162-172. doi:10.1038/sj.ejcn.1601763


Pitkanen, O. M., P. Luukkainen, et al. (2004). "Attenuated Lipid Peroxidation in Preterm Infants during Subsequent Doses of Intravenous Lipids." Biol Neonate 85(3): 184-187.

            The aim of this study was to determine whether the administration of a lipid emulsion containing less polyunsaturated fatty acids but rich in monounsaturated fatty acids causes less in vivo lipid peroxidation in preterm infants. The prospective intervention study included 13 infants with birth weights and gestational ages ranging between 1,100 and 2,660 g and from 28.4 to 32.9 weeks. All were in a stable condition and randomly allocated for a 3-hour infusion (0.16 g/kg/h) of an olive oil-based and a soybean oil + medium chain fatty acid (MCT) emulsion on 2 consecutive days. Expired pentane and plasma triglycerides (TGs) were measured before, during, and after the 3-hour infusion. Basal exhaled pentane averaged 9.4 +/- 7.0 pmol/kg/min (mean +/- SD). During the olive oil-based emulsion, exhaled pentane increased to 95.2 +/- 56.7, and during soybean oil + MCT it increased to 110 +/- 93.9 pmol/kg/min (p < 0.05 both from basal, n.s. between preparations). One hour after discontinuation of the infusion, exhaled pentane returned to 21.1 +/- 12.6 pmol/kg/min (p < 0.05 vs. basal). Combined data on expired pentane measurements demonstrated that on day 1 pentane peaked at 124 +/- 87.0 pmol/kg/min which was significantly attenuated to 57.5 +/- 24.4 pmol/kg/min after an identical dose of lipid on day 2 (p < 0.05). No difference in peak TGs was detected between the two preparations or the study days. Infusion of a constant dose of intravenous lipids on 2 subsequent days to the newborn infants is associated with a reduction in lipid peroxidation. This finding may be dependent on normal postnatal maturation or may represent an appropriate adaptive response aiming at a reduction in oxidative stress. Peroxidation of soybean oil + MCT and olive oil-based lipid emulsions was similar in the newborn infants. Copyright 2004 S. Karger AG, Basel


O'Keefe, J. H., Jr. and L. Cordain (2004). "Cardiovascular disease resulting from a diet and lifestyle at odds with our Paleolithic genome: how to become a 21st-century hunter-gatherer." Mayo Clin Proc 79(1): 101-8.

            Our genetic make-up, shaped through millions of years of evolution, determines our nutritional and activity needs. Although the human genome has remained primarily unchanged since the agricultural revolution 10,000 years ago, our diet and lifestyle have become progressively more divergent from those of our ancient ancestors. Accumulating evidence suggests that this mismatch between our modern diet and lifestyle and our Paleolithic genome is playing a substantial role in the ongoing epidemics of obesity, hypertension, diabetes, and atherosclerotic cardiovascular disease. Until 500 generations ago, all humans consumed only wild and unprocessed food foraged and hunted from their environment. These circumstances provided a diet high in lean protein, polyunsaturated fats (especially omega-3 [omega-3] fatty acids), monounsaturated fats, fiber, vitamins, minerals, antioxidants, and other beneficial phytochemicals. Historical and anthropological studies show hunter-gatherers generally to be healthy, fit, and largely free of the degenerative cardiovascular diseases common in modern societies. This review outlines the essence of our hunter-gatherer genetic legacy and suggests practical steps to re-align our modern milieu with our ancient genome in an effort to improve cardiovascular health.


Murthy, S., E. Born, et al. (2004). "Liver-X-receptor-mediated increase in ATP-binding cassette transporter A1 expression is attenuated by fatty acids in CaCo-2 cells: effect on cholesterol efflux to high-density lipoprotein." Biochem J 377(Pt 3): 545-52.

            The effect of fatty acids on LXR (liver X receptors)-mediated enhancement of ABCA1 (ATP-binding cassette transporter A1) expression and cholesterol efflux was investigated in human intestinal cells CaCo-2. LXR activation by T0901317 increased basolateral cholesterol efflux to lipoprotein particles isolated at a density of 1.21 g/ml or higher. Oleic and arachidonic acids attenuated the amount of cholesterol isolated from these particles. Stearic, linoleic and docosahexaenoic acids also decreased cholesterol efflux from basolateral membranes, with the polyunsaturated fatty acids being the most potent. Although oleic, arachidonic and docosahexaenoic acids modestly decreased ABCA1 mRNA levels in response to LXR activation, stearic and linoleic acids did not. Except for oleic acid, all fatty acids substantially attenuated an increase in ABCA1 mass secondary to LXR activation. Inhibiting acyl-CoA:cholesterol acyltransferase activity prevented the decrease in cholesterol efflux caused by oleic acid. Thus, in response to LXR activation, all fatty acids decreased the efflux of cholesterol from the basolateral membrane of CaCo-2 cells. Although modest suppression of ABCA1 gene expression by oleic, arachidonic and docosahexaenoic acids cannot be completely excluded as a mechanism, the predominant effect of fatty acids on ABCA1 expression and cholesterol efflux is at a post-transcriptional level.


Muller-Navarra, D. C., M. T. Brett, et al. (2004). "Unsaturated fatty acid content in seston and tropho-dynamic coupling in lakes." Nature 427(6969): 69-72.

            Determining the factors that control food web interactions is a key issue in ecology. The empirical relationship between nutrient loading (total phosphorus) and phytoplankton standing stock (chlorophyll a) in lakes was described about 30 years ago and is central for managing surface water quality. The efficiency with which biomass and energy are transferred through the food web and sustain the production of higher trophic levels (such as fish) declines with nutrient loading and system productivity, but the underlying mechanisms are poorly understood. Here we show that in seston (fine particles in water) during summer, specific omega3-polyunsaturated fatty acids (omega3-PUFAs), which are important for zooplankton, are significantly correlated to the trophic status of the lake. The omega3-PUFAs octadecatetraenoic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid, but not alpha-linolenic acid, decrease on a double-logarithmic scale with increasing total phosphorus. By combining the empirical relationship between EPA-to-carbon content and total phosphorus with functional models relating EPA-to-carbon content to the growth and egg production of daphnids, we predict secondary production for this key consumer. Thus, the decreasing efficiency in energy transfer with increasing lake productivity can be explained by differences in omega3-PUFA-associated food quality at the plant-animal interface.


Morise, A., C. Serougne, et al. (2004). "Effects of dietary alpha linolenic acid on cholesterol metabolism in male and female hamsters of the LPN strain." J Nutr Biochem 15(1): 51-61.

            N-3 polyunsaturated fatty acids and estrogens are recognized as protective factors of atherosclerosis, however their interactions on cholesterol metabolism remain unclear. Male and female hamsters were fed for 9 weeks diets containing 12.5% lipids and rich in either alpha-linolenic acid ("linseed" diet) or saturated fatty acids ("butter" diet). Hamsters fed the "linseed" diet exhibited lower plasma concentrations of cholesterol (-29%), total LDL (-35%) and HDL (-17%), glucose (-20%), insulin (-40%) and of the LDL-cholesterol/HDL-cholesterol ratio (-27%) than those fed the "butter" diet. In the liver, cholesterol content was 2.7-fold lower in response to the "linseed" diet, whereas the concentration of HDL receptor (SR-BI) and the activities of HMGCoA reductase and cholesterol 7alpha-hydroxylase were 30 to 50% higher than with the "butter" diet. By contrast, the LDL receptor concentration did not vary with the diet. Females exhibited higher concentration of LDL (+24%), lower concentration of plasma triglycerides (-34%), total VLDL (-46%) and VLDL-cholesterol (-37%) and of biliary phospholipids (-19%). Besides, there was also an interaction between gender and diet: in males fed the "butter" diet, plasma triglycerides and VLDL concentration, were 2 to 4 fold higher than in the other groups. These data suggest that gene and/or metabolic regulations by fatty acids could interact with that of sex hormones and explain why males are more sensitive to dietary fatty acids.


Meyer, B. J., T. A. Larkin, et al. (2004). "Limited Lipid-Lowering Effects of Regular Consumption of Whole Soybean Foods." Ann Nutr Metab 48(2): 67-78.

            AIM: To examine cardiovascular health benefits of foods containing a whole soybean extract. METHODS: The study design was a randomized, placebo-controlled crossover trial of consuming soy-based milk and yoghurt (treatment) or equivalent dairy products (control) for 5 weeks each. Twenty-six mildly hypercholesterolaemic and/or hypertensive volunteers were recruited from the community as study volunteers, of which 23 completed. Main outcome measures included clinic and ambulatory blood pressure, arterial compliance, lipids, fatty acids and isoflavones in fasted blood and 24-hour urinary isoflavone excretion. Nutrient intakes were assessed initially and after each 5-week period. Multiple regression analyses were used to determine predictor variables in statistical models; order effects were tested by repeated measures ANOVA. Changes in Lp(a) were determined by Wilcoxon signed ranks tests; other differences between treatment and control were assessed by t tests. RESULTS: Plasma and urinary isoflavones were markedly increased by whole soy supplementation but there were no overall differences in plasma lipids, blood pressure or arterial compliance between the soy and dairy diets. However, in 8 equol-positive subjects (equol detected in either plasma or urine), retrospective analysis revealed significant reductions in total cholesterol (8.5%), LDL cholesterol (10%), LDL:HDL ratio (13.5%), plasma triglycerides (21%) and lipoprotein(a) (11%) with the soy diet. These reductions were independent of changes in polyunsaturated fat and other macronutrient intakes. CONCLUSIONS: Regular consumption of whole soybean milk and yogurt products had no effect on plasma lipids, blood pressure or arterial compliance in at-risk subjects, despite substantially increasing isoflavone levels in blood and urine. Retrospective analysis suggests that improvement of plasma lipids may have been limited to equol-positive subjects. Copyright 2004 S. Karger AG, Basel


Macdonald, H. M., S. A. New, et al. (2004). "Nutritional associations with bone loss during the menopausal transition: evidence of a beneficial effect of calcium, alcohol, and fruit and vegetable nutrients and of a detrimental effect of fatty acids." Am J Clin Nutr 79(1): 155-65.

            BACKGROUND: The menopausal transition is characterized by rapid bone loss. Few data exist on the role of nutrition. OBJECTIVE: The objective of the study was to ascertain which dietary factors influence perimenopausal skeletal loss. DESIGN: A longitudinal study was conducted of 891 women aged 45-55 y at baseline and 50-59 y at follow-up 5-7 y later. Bone mineral density (BMD) was measured by using dual-energy X-ray absorptiometry at the lumbar spine and femoral neck (FN). Nutrient intakes were assessed after the baseline visit and 5 y later, by using the same food-frequency questionnaire. RESULTS: After adjustment for energy intake and other confounders, higher intakes of calcium were correlated with change in FN BMD (ie, reduced loss) (r = 0.073, P < 0.05), and the intake of modest amounts of alcohol was associated with less lumbar spine bone loss (P < 0.01 for quartile of alcohol intake). Greater FN BMD loss was associated with increased intake of polyunsaturated fatty acids (r = -0.110, P < 0.01), monounsaturated fatty acids (r = -0.069, P < 0.05), retinol (r = -0.067; P < 0.05), and vitamin E (r = -0.110; P < 0.01). The latter 2 nutrients were highly correlated with polyunsaturated fatty acids. For premenopausal women, calcium and nutrients found in fruit and vegetables (vitamin C, magnesium, and potassium) were associated with FN BMD, and calcium, vitamin C, and magnesium were associated with change in FN BMD. CONCLUSIONS: Although menopausal status and hormone replacement therapy use dominate women's bone health, diet may influence early postmenopausal bone loss. Fruit and vegetable intake may protect against premenopausal bone loss.


Kankaanpaa, P., B. Yang, et al. (2004). "Effects of polyunsaturated fatty acids in growth medium on lipid composition and on physicochemical surface properties of lactobacilli." Appl Environ Microbiol 70(1): 129-36.

            Most probiotic lactobacilli adhere to intestinal surfaces, a phenomenon influenced by free polyunsaturated fatty acids (PUFA). The present study investigated whether free linoleic acid, gamma-linolenic acid, arachidonic acid, alpha-linolenic acid, or docosahexaenoic acid in the growth medium alters the fatty acid composition of lactobacilli and their physical characteristics. The most abundant bacterial fatty acids identified were oleic, vaccenic, and dihydrosterculic acids. PUFA, especially conjugated linoleic acid (CLA) isomers and gamma-linolenic, eicosapentaenoic, docosahexaenoic, and alpha-linolenic acids, also were identified in lactobacilli. When lactobacilli were cultured in MRS broth supplemented with various free PUFA, the incorporation of a given PUFA into bacterial fatty acids was clearly observed. Moreover, PUFA supplementation also resulted in PUFA-dependent changes in the proportions of other fatty acids; major interconversions were seen in octadecanoic acids (18:1), their methylenated derivatives (19:cyc), and CLA. Intermittent changes in eicosapentaenoic acid proportions also were noted. These results were paralleled by minor changes in the hydrophilic or hydrophobic characteristics of lactobacilli, suggesting that PUFA interfere with microbial adhesion to intestinal surfaces through other mechanisms. In conclusion, we have demonstrated that free PUFA in the growth medium induce changes in bacterial fatty acids in relation to the regulation of the degree of fatty acid unsaturation, cyclization, and proportions of CLA and PUFA containing 20 to 22 carbons. The potential role of lactobacilli as regulators of PUFA absorption may represent another means by which probiotics could redirect the delicate balance of inflammatory mediators derived from PUFA within the inflamed intestine.


Kalmijn, S., M. P. van Boxtel, et al. (2004). "Dietary intake of fatty acids and fish in relation to cognitive performance at middle age." Neurology 62(2): 275-80.

            OBJECTIVE: To examine the associations of fatty acid and fish intake with cognitive function. METHODS: Data are from a cross-sectional population-based study among 1,613 subjects ranging from 45 to 70 years old. From 1995 until 2000, an extensive cognitive battery was administered and compound scores were constructed for memory, psychomotor speed, cognitive flexibility (i.e., higher order information processing), and overall cognition. A self-administered food-frequency questionnaire was used to assess habitual food consumption. The risk of impaired cognitive function (lowest 10% of the compound score) according to the energy adjusted intake of fatty acids was assessed with logistic regression, adjusting for age, sex, education, smoking, alcohol consumption, and energy intake. RESULTS: Marine omega-3 polyunsaturated fatty acids (PUFA) (eicosapentaenoic acid and docosahexaenoic acid) were inversely related to the risk of impaired overall cognitive function and speed (per SD increase: OR = 0.81, 95% CI 0.66 to 1.00 and OR = 0.72, 95% CI 0.57 to 0.90). Results for fatty fish consumption were similarly inverse. Higher dietary cholesterol intake was significantly associated with an increased risk of impaired memory and flexibility (per SD increase: OR = 1.27, 95% CI 1.02 to 1.57 and OR = 1.26, 95% CI 1.01 to 1.57). Per SD increase in saturated fat intake, the risk of impaired memory, speed, and flexibility was also increased, although not significantly. CONCLUSIONS: Fatty fish and marine omega-3 PUFA consumption was associated with a reduced risk and intake of cholesterol and saturated fat with an increased risk of impaired cognitive function in this middle-aged population.


Iribarren, C., J. H. Markovitz, et al. (2004). "Dietary intake of n-3, n-6 fatty acids and fish: Relationship with hostility in young adults-the CARDIA study." Eur J Clin Nutr 58(1): 24-31.

            BACKGROUND:: Hostility has been shown to predict both the development and manifestation of coronary disease. Examining the inter-relation of dietary intake of fish and of polyunsaturated (n-3 and n-6) essential fatty acids with hostility may provide additional insights into the cardioprotective effect of dietary fish and polyunsaturated fatty acids. OBJECTIVE:: To examine the association of dietary n-3, n-6 fatty acids and fish with level of hostility in a sample of 3581 urban white and black young adults. DESIGN:: Cross-sectional observational study as part of an ongoing cohort study. A dietary assessment in 1992-1993 and measurement of hostility and other covariates in 1990-1991 were used in the analysis. RESULTS:: The multivariate odds ratios of scoring in the upper quartile of hostility (adjusting for age, sex, race, field center, educational attainment, marital status, body mass index, smoking, alcohol consumption and physical activity) associated with one standard deviation increase in docosahexaenoic acid (DHA, 22:6) intake was 0.90 (95% CI=0.82-0.98; P=0.02). Consumption of any fish rich in n-3 fatty acids, compared to no consumption, was also independently associated with lower odds of high hostility (OR=0.82; 95% CI=0.69-0.97; P=0.02). CONCLUSIONS:: These results suggest that high dietary intake of DHA and consumption of fish rich in n-3 fatty acids may be related to lower likelihood of high hostility in young adulthood. The association between dietary n-3 fatty acids and hostile personality merits further research.European Journal of Clinical Nutrition (2004) 58, 24-31. doi:10.1038/sj.ejcn.1601739


Huang, X. F., X. Xin, et al. (2004). "Role of fat amount and type in ameliorating diet-induced obesity: insights at the level of hypothalamic arcuate nucleus leptin receptor, neuropeptide Y and pro-opiomelanocortin mRNA expression." Diabetes Obes Metab 6(1): 35-44.

            AIMS: Dietary fatty acid profile, independent of caloric percent of fat, is a major regulator of body adiposity. This study examined the effects of dietary fat amount and types on fat storage and hypothalamic gene expression in the mouse model of chronic diet-induced obesity. METHODS: The dietary interventions were in twofold: (1) the obesity was induced by a 13-week obesogenic fat diet compared with a low-fat (LF) diet, and (2) the reversibility was tested by using high n-3 polyunsaturated fat (PUFA) and LF diets. Fifty-four C57Bl/6 mice were fed a high-fat (59% in kcal) diet for 13 weeks and then classified as diet-induced obese (DIO) or diet-resistant (DR) mice according to upper and lower tertiles of body weight gain. The DIO mice were then subdivided into three groups for a 6-week secondary dietary intervention. Two of the groups were switched to either a high n-3 PUFA (DIO-n3) or a low-fat (10% in kcal, DIO-LF) diet, whereas the third (controls) and DR mice continued on the initial high-fat diet. Food efficiency was calculated as weekly body weight gain per gram of food intake. RESULTS: After switching the DIO mice to the n-3 PUFA or LF diet, their body weights were reduced to the level of the DR and LF mice. The food efficiencies were, from the highest to lowest, in the order: DIO > LF > DR > DIO-LF > DIO-n3. Using quantitative in situ hybridization, we found that the DIO mice had higher levels of leptin receptor (LR, +290%, p < 0.005) and neuropeptide Y (NPY, +25%, p < 0.05) mRNA expression in the hypothalamic arcuate nucleus (Arc) than the DR mice, whereas the level of pro-opiomelanocortin (POMC) mRNA expression was significantly reduced (-45%, p < 0.01). All effects that were essentially returned to DR levels by the change to the n-3 PUFA diet and, with the exception of a failure to normalize Arc NPY mRNA levels, by the change to LF diet. CONCLUSIONS: Taken together, the present results show that both change in level and quality of dietary fat can potently alter hypothalamic neuropeptide expression and result in effective amelioration of diet-induced obesity. Interestingly, the n-3 PUFA diet when fed to already obese mice produced a pattern of hypothalamic gene expression similar to that in obesity resistant (DR) mice. It remains to be determined if the effects of n-3 fatty acids on brain neuropeptide gene expression are direct or indirect.


Hammad, H., H. J. de Heer, et al. (2004). "Activation of peroxisome proliferator-activated receptor-gamma in dendritic cells inhibits the development of eosinophilic airway inflammation in a mouse model of asthma." Am J Pathol 164(1): 263-71.

            Peroxisome proliferator-activated receptors (PPARs) are activated by an array of polyunsaturated fatty acid derivatives, oxidized fatty acids, and phospholipids and are proposed to be important modulators of immune and inflammatory responses. Recently, we showed that activation of PPAR-gamma alters the maturation process of dendritic cells (DCs), the most potent antigen-presenting cells. In the present report, we investigated the possibility that, by targeting DCs, PPAR-gamma activation may be involved in the regulation of the pulmonary immune response to allergens. Using a model of sensitization, based on the intratracheal transfer of ovalbumin (OVA)-pulsed DCs, we show that rosiglitazone, a selective PPAR-gamma agonist, reduces the proliferation of Ag-specific T cells in the draining mediastinal lymph nodes but, surprisingly enough, dramatically increases the production of the immunoregulatory cytokine interleukin (IL)-10 by T cells, as compared to control mice sensitized with OVA-pulsed DCs. After aerosol challenge, the recruitment of eosinophils in the bronchoalveolar lavage fluids was strongly reduced compared to control mice. Finally, T cells from the mediastinal lymph nodes produced higher amounts of IL-10 and interferon-gamma. Inhibition of IL-10 activity with anti-IL-10R antibodies partly restored the inflammation. The specificity of the phenomenon was confirmed by treating OVA-pulsed DCs with ciglitazone, another PPAR-gamma agonist, and by using GW9662, a PPAR-gamma antagonist. Our data suggest that PPAR-gamma activation prevents induction of Th2-dependent eosinophilic airway inflammation and might contribute to immune homeostasis in the lung.


Guillou, H., S. D'Andrea, et al. (2004). "The surprising diversity of Delta6-desaturase substrates." Biochem Soc Trans 32(Pt 1): 86-7.

            A single gene encoding a Delta6-desaturase (FADS2) has been isolated and characterized in mammalian species. This Delta6-desaturase plays a major role in the biosynthesis of PUFAs (polyunsaturated fatty acids). It catalyses the rate-limiting desaturation of linoleic acid (C(18:2) n -6) and alpha-linolenic acid (C(18:3) n -3) required for the biosynthesis of long-chain PUFAs. Moreover, recent studies have provided strong evidence that this Delta6-desaturase also acts on 24-carbon PUFAs of both the n -6 and n -3 series. Another substrate of this Delta6-desaturase has been identified through complementary works from different investigators. This Delta6-desaturase acts on a saturated fatty acid, palmitic acid (C(16:0)), leading to the newly characterized biosynthesis of hexadecenoic acid (C(16:1) n -10) or sapienate.


Goodfriend, T. L., D. L. Ball, et al. (2004). "Epoxy-Keto Derivative of Linoleic Acid Stimulates Aldosterone Secretion." Hypertension.

            Plasma levels of aldosterone are not always predictable from the activity of renin and the concentration of potassium. Among the unexplained are elevated levels of aldosterone in some obese humans. Obesity is characterized by increased plasma fatty acids and oxidative stress. We postulated that oxidized fatty acids stimulate aldosteronogenesis. The most readily oxidized fatty acids are the polyunsaturated, and the most abundant of those is linoleic acid. We tested oxidized derivatives of linoleic acid for effects on rat adrenal cells. One derivative, 12,13-epoxy-9-keto-10(trans)-octadecenoic acid (EKODE), was particularly potent. EKODE stimulated aldosteronogenesis at concentrations from 0.5 to 5 micro mol/L, and inhibited aldosteronogenesis at higher doses. EKODE's stimulatory effect was most prominent when angiotensin and potassium effects were submaximal. The lipid's mechanism of action was on the early pathway leading to pregnenolone; its action was inhibited by atrial natriuretic peptide. Plasma EKODE was measured by liquid chromatography/mass spectrometry. All human plasmas tested contained EKODE in concentrations ranging from 10(-9) to 5x10(-7) mol/L. In samples from 24 adults, levels of EKODE correlated directly with aldosterone (r=0.53, P=0.007). In the 12 blacks in that cohort, EKODE also correlated with body mass index and systolic pressure. Those other correlations were not seen in white subjects. The results suggest that oxidized derivatives of polyunsaturated fatty acids other than arachidonic are biologically active. Compounds like EKODE, derived from linoleic acid, may affect adrenal steroid production in humans and mediate some of the deleterious effects of obesity and oxidative stress, especially in blacks.


Ferreri, C., A. Samadi, et al. (2004). "Regioselective cis-trans isomerization of arachidonic double bonds by thiyl radicals: the influence of phospholipid supramolecular organization." J Am Chem Soc 126(4): 1063-72.

            Trans unsaturated fatty acids in humans may be originated by two different contributions. The exogenous track is due to dietary supplementation of trans fats and the endogenous path deals with free-radical-catalyzed cis-trans isomerization of fatty acids. Arachidonic acid residue (5c,8c,11c,14c-20:4), which has only two out of the four double bonds deriving from the diet, was used to differentiate the two paths and to assess the importance of a radical reaction. A detailed study on the formation of trans phospholipids catalyzed by the HOCH(2)CH(2)S(*) radical was carried out on l-alpha-phosphatidylcholine from egg lecithin and 1-stearoyl-2-arachidonoyl-l-alpha-phosphatidylcholine (SAPC) in homogeneous solution or in large unilamellar vesicles (LUVET). Thiyl radicals were generated from the corresponding thiol by either gamma-irradiation or UV photolysis, and the reaction course was followed by GC, Ag/TLC, and (13)C NMR analyses. The isomerization was found to be independent of cis double bond location (random process) in i-PrOH solution. In the case of vesicles, the supramolecular organization of lipids produced a dramatic change of the isomerization outcome: (i) in egg lecithin, the reactivity of arachidonate moieties is higher than that of oleate and linoleate residues, (ii) in the linoleate residues of egg lecithin, the 9t,12c-18:2 isomer prevailed on the 9c,12t-18:2 isomer (3:1 ratio), and (iii) a regioselective isomerization of SAPC arachidonate residues occurred in the 5 and 8 positions. This effect of "positional preference" indicates that thiyl radicals entering the hydrophobic region of the membrane bilayer start to isomerize polyunsaturated fatty acid residues having the double bonds nearest to the membrane surfaces. We propose that arachidonic acid and its trans isomers can function as biomarkers in membranes for distinguishing the two trans fatty acid-forming pathways.


Engelmann, B. (2004). "Plasmalogens: targets for oxidants and major lipophilic antioxidants." Biochem Soc Trans 32(Pt 1): 147-50.

            Cellular membranes and plasma lipoproteins are less efficiently protected against oxidative stress than the various aqueous compartments of mammalian organisms. Here, previous results on the role of plasmalogens in lipid oxidation are evaluated on the basis of criteria required for an antioxidant. The plasmalogen-specific enol ether double bond is targeted by a vast variety of oxidants, including peroxyl radicals, metal ions, singlet oxygen and halogenating species. Oxidation of the vinyl ether markedly prevents the oxidation of highly polyunsaturated fatty acids, and products of plasmalogen degradation do not propagate lipid oxidation. This protection is also demonstrated intramolecularly, thus ascertaining the function of plasmalogens as a major storage pool for polyunsaturated fatty acids. Although cells rapidly incorporate and synthesize plasmalogens de novo, their plasmalogen contents can be deliberately increased by supplementation with precursors. Thus plasmalogens terminate lipid-oxidation processes, are present in adequate locations at sufficient concentrations, and are rapidly regenerated, classifying them as efficient antioxidants in vitro. Future work should address the in vivo role of plasmalogens in lipid oxidation and the biological function of plasmalogen interactions with oxidants.


Dwyer, J. H., H. Allayee, et al. (2004). "Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis." N Engl J Med 350(1): 29-37.

            BACKGROUND: Leukotrienes are inflammatory mediators generated from arachidonic acid (polyunsaturated n-6 fatty acid) by the enzyme 5-lipoxygenase. Since atherosclerosis involves arterial inflammation, we hypothesized that a polymorphism in the 5-lipoxygenase gene promoter could relate to atherosclerosis in humans and that this effect could interact with the dietary intake of competing 5-lipoxygenase substrates. METHODS: We determined 5-lipoxygenase genotypes, carotid-artery intima-media thickness, and markers of inflammation in a randomly sampled cohort of 470 healthy, middle-aged women and men from the Los Angeles Atherosclerosis Study. Dietary arachidonic acid and marine n-3 fatty acids (including a competing 5-lipoxygenase substrate that reduces the production of inflammatory leukotrienes) were measured with the use of six 24-hour recalls of food intake. RESULTS: Variant 5-lipoxygenase genotypes (lacking the common allele) were found in 6.0 percent of the cohort. Mean (+/-SE) intima-media thickness adjusted for age, sex, height, and racial or ethnic group was increased by 80+/-19 microm (95 percent confidence interval, 43 to 116; P<0.001) among carriers of two variant alleles, as compared with carriers of the common (wild-type) allele. In multivariate analysis, the increase in intima-media thickness among carriers of two variant alleles (62 microm, P<0.001) was similar in this cohort to that associated with diabetes (64 microm, P=0.01), the strongest common cardiovascular risk factor. Increased dietary arachidonic acid significantly enhanced the apparent atherogenic effect of genotype, whereas increased dietary intake of n-3 fatty acids blunted the effect. Finally, the plasma level of C-reactive protein, a marker of inflammation, was increased by a factor of 2 among carriers of two variant alleles as compared with that among carriers of the common allele. CONCLUSIONS: Variant 5-lipoxygenase genotypes identify a subpopulation with increased atherosclerosis. The observed diet-gene interactions further suggest that dietary n-6 polyunsaturated fatty acids promote, whereas marine n-3 fatty acids inhibit, leukotriene-mediated inflammation that leads to atherosclerosis in this subpopulation.


Dixon, G., J. Nolan, et al. (2004). "Arachidonic acid, palmitic acid and glucose are important for the modulation of clonal pancreatic beta-cell insulin secretion, growth and functional integrity." Clin Sci (Lond) 106(2): 191-9.

            Insulin-resistant states such as obesity can result in an increase in the function and mass of pancreatic beta-cells, so that insulin secretion is up-regulated and Type II diabetes does not develop. However, expansion of beta-cell mass is not indefinite and may well decrease with time. Changes in circulating concentrations of nutritional factors, such as fatty acids and/or glucose, may lead to a reduction in beta-cell mass in vivo. Few previous studies have attempted to explore the interplay between glucose, amino acids and fatty acids with respect to beta-cell mass and functional integrity. In the present study, we demonstrate that culture of clonal BRIN-BD11 cells for 24 h with the polyunsaturated fatty acid arachidonic acid (AA) increased beta-cell proliferation and enhanced alanine-stimulated insulin secretion. These effects of AA were associated with significant decreases in the cellular consumption of D-glucose and L-alanine as well as decreased rates of production of nitric oxide and ammonia. Conversely 24 h exposure to the saturated fatty acid palmitic acid (PA) was found to decrease beta-cell viability (by increasing apoptosis), increase the intracellular concentration of triacylglycerol (triglyceride), while inhibiting alanine-stimulated insulin secretion. These effects of PA were associated with significant increases in D-glucose and L-glutamine consumption as well as nitric oxide and ammonia production. However, L-alanine consumption was decreased in the presence of PA. The effects of AA, but not PA, were additionally dependent on glucose concentration. These studies indicate that AA may have a critical role in maintaining the appropriate mass and function of islet beta-cells by influencing rates of cell proliferation and insulin secretion. This regulatory effect may be compromised by high circulating levels of glucose and/or PA, both of which are elevated in Type II diabetes and may impact upon dysfunctional and apoptotic intracellular events in the beta-cell.


Ding, J. L., E. H. Lim, et al. (2004). "Expression of recombinant vitellogenin in the yeast Pichia pastoris." Biotechnol Bioeng 85(3): 330-9.

            Vitellogenin (Vtg) plays vital roles as precursor to the yolk proteins and as carrier for lipids, carbohydrates, phosphates, metal ions, vitamins, and hormones into the oocytes during the massive deposition of yolk nutrients for subsequent nourishment of the developing embryos. Reproductive success is highly sensitive to the nutritional quality of the broodstock diet, which greatly affects the egg and larval viability. We present a novel strategy for genetically engineering a Pichia pastoris yeast strain that constitutively produces recombinant Vtg (rVtg), for application as an enriched feed. The tilapia Oreochromis aureus Vtg (OaVtg) cDNA (5.3 kb) was cloned into a nonsecretory pGAPZA vector. Clones containing up to 31 copies of glyceraldehyde-3-phosphate dehydrogenase (GAP)-promoter-driven Vtg expression cassettes were isolated. These clones expressed a membrane-associated intracellular rVtg protein of 194 kDa, constituting up to 1.16% of total protein. To facilitate future purification of rVtg, we explored the possibility of secreting rVtg using the native Vtg secretion signal and the alpha-factor secretion signal of Saccharomyces cerevisiae. However, neither signal promoted the secretion of rVtg. The clones maximally expressed rVtg at 23 degrees C, reaching a peak at 22 h in shake flasks and 16 h in a fermentor. The clones exhibited a significant increase in essential amino acids and long-chain polyunsaturated fatty acids, which are important for its application as a high-quality nutrient feed.


Das, U. N. (2004). "Long-chain polyunsaturated fatty acids interact with nitric oxide, superoxide anion, and transforming growth factor-beta to prevent human essential hypertension." Eur J Clin Nutr 58(2): 195-203.

            Patients with uncontrolled essential hypertension have elevated concentrations of superoxide anion (O(2)(-*)), hydrogen peroxide (H(2)O(2)), lipid peroxides, endothelin, and transforming growth factor-beta (TGF-beta) with a simultaneous decrease in endothelial nitric oxide (eNO), superoxide dismutase (SOD), vitamin E, and long-chain polyunsaturated fatty acids (LCPUFAs). Physiological concentrations of angiotensin II activate NAD(P)H oxidase and trigger free radical generation (especially that of O(2)(-*)). Normally, angiotensin II-induced oxidative stress is abrogated by adequate production and release of eNO, which quenches O(2)(-*) to restore normotension. Angiotensin II also stimulates the production of endothelin and TGF-beta. TGF-beta enhances NO generation, which in turn suppresses TGF-beta production. Thus, NO has a regulatory role on TGF-beta production and is also a physiological antagonist of endothelin. Antihypertensive drugs suppress the production of O(2)(-*) and TGF-beta and enhance eNO synthesis to bring about their beneficial actions. LCPUFAs suppress angiotensin-converting enzyme (ACE) activity, reduce angiotensin II formation, enhance eNO generation, and suppress TGF-beta expression. Perinatal supplementation of LCPUFAs decreases insulin resistance and prevents the development of hypertension in adult life, whereas deficiency of LCPUFAs in the perinatal period results in raised blood pressure later in life. Patients with essential hypertension have low concentrations of various LCPUFAs in their plasma phospholipid fraction. Based on this, it is proposed that LCPUFAs serve as endogenous regulators of ACE activity, O(2)(-*), eNO generation, and TGF-beta expression. Further, LCPUFAs have actions similar to statins, inhibit (especially omega-3 fatty acids) cyclooxygenase activity and suppress the synthesis of proinflammatory cytokines, and activate the parasympathetic nervous system, all actions that reduce the risk of major vascular events. Hence, it is proposed that availability of adequate amounts of LCPUFAs during the critical periods of growth prevents the development of hypertension in adulthood.European Journal of Clinical Nutrition (2004) 58, 195-203. doi:10.1038/sj.ejcn.1601766


Cho, S. H., M. L. Jahncke, et al. (2004). "Nutritional composition and microflora of the fresh and fermented skate (Raja Kenojei) skins." Int J Food Sci Nutr 55(1): 45-51.

            The proximate compositions of fresh and fermented skate skin were each 75.95% and 74.5% moisture, 22.7% and 21.8% protein, 0.5% and 0.7% lipid and 0.6% and 0.9% ash, respectively. The predominant minerals were potassium and phosphorus (i.e. 53.5 and 33.0 mg/100 g in fresh skin, and 10.46 and 10.51 mg/100 g in fermented skin, respectively). Amino acid concentrations were lower in the fermented skin compared with the fresh skin. Histidine, glycine, alanine and glutamic acid were the major free amino acids in both skins. Palmitic acid (C16:0) was the major fatty acid in both fresh (16.68%) and fermented (20.38%) skate skin. Omega-3 polyunsaturated fatty acids were higher in fresh skin (22.17%) and fermented skin (24.54%) compared with omega-6 polyunsaturated fatty acids. The predominant microflora present in the both fresh and fermented skin were Photobacterium sp. and Vibrio sp. Total plate counts for the fresh and fermented skin were 2.4x10(4) CFU/g and 7.7x10(7) CFU/g, respectively.


Caro, A. A. and A. I. Cederbaum (2004). "Oxidative stress, toxicology, and pharmacology of cyp2e1 *." Annu Rev Pharmacol Toxicol 44: 27-42.

            This review describes some of the biochemical and toxicological properties of CYP2E1, especially as it relates to alcohol metabolism and toxicity and the establishment of human hepatoma HepG2 cell lines that overexpress human CYP2E1. Ethanol, polyunsaturated fatty acids, and iron were found to be cytotoxic in HepG2 cells that overexpress CYP2E1. GSH appears to be essential in protecting HepG2 cells against the CYP2E1-dependent cytotoxicity, and GSH levels were elevated owing to a twofold increase in activity and expression of glutamate cysteine ligase. We suggest that this up-regulation of GSH synthesis was an adaptive response to attenuate CYP2E1-dependent oxidative stress and toxicity. Induction of a state of oxidative stress appears to play a central role in the CYP2E1-dependent cytotoxicity. Mitochondrial membrane potential decreased in the CYP2E1-expressing HepG2 cells, and this decrease shared similar characteristics with the developing toxicity. Alcohol-dependent liver injury is likely to be a multifactorial process involving several mechanisms. We believe that the linkage between CYP2E1-dependent oxidative stress, mitochondrial injury, and GSH homeostasis contribute to the toxic actions of ethanol on the liver.


Cabre, A., J. Girona, et al. (2004). "Aldehydes mediate tissue factor induction: a possible mechanism linking lipid peroxidation to thrombotic events." J Cell Physiol 198(2): 230-6.

            Tissue factor (TF), which is expressed in atherosclerotic plaques and colocalizes with oxidized lipids, initiates the thrombogenic process. We have analyzed the effect of aldehydes derived from peroxidation of polyunsaturated fatty acids on TF expression in human vascular smooth muscle cells (HVSMC). Our results demonstrate that hexanal and 2,4-decadienal (2,4-DDE), two apolar aldehydes, increase TF expression. Exposure of HVSMC to hexanal for 2 h led to TF protein levels up to seven times higher than untreated cells whereas 2,4-DDE for 30 min led to them being up to 2.2 times higher. This induction of TF antigen by aldehydes correlates with an increase in TF mRNA levels. Electrophoretic mobility shift assays (EMSAs) showed that the binding activity of the transcription factor AP-1 (c-Fos/c-Jun) to TF promoter was elevated in response to these oxidation products. This enhancement was associated to an increase of c-fos transcriptional activity, which was reversible by pretreatment with simvastatin. We conclude that the induction of TF by aldehydes might contribute to the severity of atherogenesis.


Buckley, M. S., A. D. Goff, et al. (2004). "Fish oil interaction with warfarin." Ann Pharmacother 38(1): 50-2.

            OBJECTIVE: To report a case of elevated international normalized ratio (INR) in a patient taking fish oil and warfarin. CASE SUMMARY: A 67-year-old white woman had been taking warfarin for 1(1/2) years due to recurrent transient ischemic attacks. Her medical history included hypothyroidism, hyperlipidemia, osteopenia, hypertension, and coronary artery disease. She also experienced an inferior myocardial infarction in 1995 requiring angioplasty, surgical repair of her femoral artery in 1995, and hernia repair in 1996. This patient has her INR checked in the anticoagulation clinic and is followed monthly by the clinical pharmacist. Prior to the interaction, her INR was therapeutic for 5 months while she was taking warfarin 1.5 mg/d. The patient admitted to doubling her fish oil dose from 1000 to 2000 mg/d. Without dietary, lifestyle, or medication changes, the INR increased from 2.8 to 4.3 within 1 month. The INR decreased to 1.6 one week after subsequent fish oil reduction, necessitating a return to the original warfarin dosing regimen. DISCUSSION: Fish oil supplementation could have provided additional anticoagulation with warfarin therapy. Fish oil, an omega-3 polyunsaturated fatty acid, consists of eicosapentaenoic acid and docosahexaenoic acid. This fatty acid may affect platelet aggregation and/or vitamin K-dependent coagulation factors. Omega-3 fatty acids may lower thromboxane A(2) supplies within the platelet as well as decrease factor VII levels. Although controversial, this case report illustrates that fish oil can provide additive anticoagulant effects when given with warfarin. CONCLUSIONS: This case reveals a significant rise in INR after the dose of concomitant fish oil was doubled. Patients undergoing anticoagulation therapy with warfarin should be educated about and monitored for possible drug-herb interactions. Pharmacists can play a crucial role in identifying possible drug interactions by asking patients taking warfarin about herbal and other alternative medicine product use.


Blesbois, E., V. Douard, et al. (2004). "Effects of n-3 polyunsaturated dietary supplementation on the reproductive capacity of male turkeys." Theriogenology 61(2-3): 537-49.

            To measure the effects of dietary n-3 polyunsaturated fatty acid (PUFA) supplementation on the reproductive capacity of adult male turkeys in industrial flocks, the males of 22 commercial farms were fed either a standard diet or a fish oil diet enriched in n-3 PUFAs. The fatty acid composition of the spermatozoa and reproductive performance were measured throughout the reproductive period. The fish oil diet very effectively increased the percentage of n-3 fatty acids (FA) (22:5n-3 and 22:6n-3) in spermatozoa and correspondingly decreased the percentage of n-6 PUFAs (20:4-6 and 22:4n-6): the n-3/n-6 ratio in spermatozoa fatty acids were 0.04-0.07 with the standard diet and 0.32-0.4 with the fish oil diet. These changes did not affect the spermatozoa content of n-9 PUFAs, particularly of 22:3n-9 which is abundant in turkey spermatozoa (9-12% of the total fatty acids). The supplementation was effective in the middle as at the end of the reproductive period. The reproductive capacity of males was modified by the diet and the positive effect of the n-3 supplemented diet increased with age (increase in hatching rates of nearly 2 points at 48-58 weeks for males fed fish oil diet). These results indicate that an increase in the dietary ratio of n-3/n-6 PUFAs is valuable to sustain the reproductive capacity of male turkeys especially when they are getting older.


Artwohl, M., M. Roden, et al. (2004). "Free fatty acids trigger apoptosis and inhibit cell cycle progression in human vascular endothelial cells." Faseb J 18(1): 146-8.

            Plasma free fatty acid (FFA) concentrations are increased in states of insulin resistance and impair endothelial function. Because the underlying mechanisms are largely unknown, we examined selected, purified FFAs' (100-300 micromol/l, 24-48 h) action on apoptosis, cell cycle distribution, and associated gene/protein expression in human umbilical vein endothelial cells (HUVECs). Stearic acid, but not oleic acid, time and concentration dependently increased endothelial apoptosis by fivefold (n=6, P<0.01), whereas polyunsaturated FFAs (PUFAs; linoleic, gamma-linolenic, and arachidonic acid) exerted proapoptotic activity only at 300 micromol/l (P<0.05). Proapoptotic FFA action increased with FFAs' number of double bonds and with protein expression of the apoptosis promotor bak. The G0/G1 cell cycle arrest (n=6, P<0.05) induced by stearic acid (+14%) and PUFAs (+30%) is reflected by up-regulation of p21(WAF-1/Cip1). In addition, all FFAs concentration dependently reduced (P<0.05) gene/protein expression of clusterin (-54%), NF-kappaB's inhibitor, IkappaBalpha (-50%), endothelin-1 (-44%), and endothelial NO synthase (-44%). Plasma samples obtained from individuals with elevated plasma FFAs (372+/-22 micromol/l) increased endothelial apoptosis by 4.2-fold (P<0.001, n=10) compared with intra-individually matched low plasma FFA (56+/-21 micromol/l) conditions, underlining the results obtained by defined FFA stimulation. In conclusion, FFA structure differently affects endothelial cell proliferation and apoptosis, both representing key factors in the development of micro- and macrovascular dysfunction.


Araya, J., R. Rodrigo, et al. (2004). "Increase in long-chain polyunsaturated fatty acid n-6/n-3 ratio in relation to hepatic steatosis in non-alcoholic fatty liver disease patients." Clin Sci (Lond).

            Hepatic steatosis is a major feature associated with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to assess the levels of polyunsaturated fatty acids (PUFA) in liver total lipids, triacylglycerols and phospholipids of NAFLD patients, in relation to those in adipose tissue and hepatic indexes related to oxidative stress, as factors contributing to hepatic steatosis. Eleven control subjects and nineteen patients with NAFLD were studied. Analysis of liver and abdominal adipose tissue fatty acids was carried out by gas liquid chromatography. The liver content of protein carbonyl groups and malondialdehyde were taken an indexes related to oxidative stress. NAFLD patients showed depletion of long-chain PUFA (LCPUFA) of the n-6 and n-3 series in liver triacylglycerols, with reduced 20:4n-6/18:2n-6 and (20:5n-3 + 22:6n-3):18:3n-3 ratios, whereas liver phospholipids contained higher n-6 and lower n-3 LCPUFA. These findings were accompanied by an enhancement of (i) n-6/n-3 ratio in liver and adipose tissue, (ii) 18:1n-9 trans levels in adipose tissue, and (iii) hepatic lipid peroxidation and protein oxidation indexes. It is concluded that a marked enhancement in LCPUFA n-6/n-3 ratio occurs in the liver of NAFLD patients, a condition that may favor lipid synthesis over oxidation and secretion, thereby leading to steatosis. Depletion of hepatic LCPUFA may result from both a defective PUFA desaturation, due to inadequate intake of precursors such as 18:3n-3 and higher intake of the 18:1n-9 trans isomer leading to desaturase inhibition, and from a higher peroxidation of LCPUFA due to oxidative stress.


Alexander Leaf, D., M. T. Kleinman, et al. (2004). "The effects of exercise on markers of lipid peroxidation in renal dialysis patients compared with control subjects." Am J Med Sci 327(1): 9-14.

            SUMMARY: ABSTRACT Purpose:The purpose of this study was to compare the susceptibility to exercise-induced lipid peroxidation of patients on chronic maintenance dialysis (CMD) and non-CMD control subjects.Design:Cross-sectional comparison of exercise-induced changes in breath ethane and pentane flux between patients on CMD (group A) and an age-, gender-, medical diagnosis-, smoking-, and ethanol consumption-matched comparison group (group B). Breath ethane and pentane were measured at rest before exercise, during cardiopulmonary exercise stress testing (CPX) at lactic acidosis threshold (Vo2lat), and 5 minutes after CPX.Results:Group comparisons of clinical characteristics reveal that the groups were similar in terms of age, ethnicity, comorbid diagnoses, prevalence of medication use, BMI, measurements of aerobic exercise capacity, cigarette smoking and ethanol consumption behaviors. All subjects successfully completed the CPX protocol achieving Vo2lat. There were significant differences in breath ethane flux between group A and B subjects, with greater pre-exercise, Vo2lat, and postexercise ethane levels in group A compared with group B subjects, and significant group differences, with lower breath ethane/pentane flux ratios at rest, Vo2lat, and recovery with lower ratios in group B than group A subjects.Discussion/Conclusions:This study shows that patients on CMD have greater lipid peroxidation compared with control subjects at rest and during and after physical exercise. In addition, compared with control subjects, patients on CMD preferentially peroxidize n-3 polyunsaturated fatty acids at rest and during physical exercise and recovery. The lipid peroxidation profile may result in an unfavorable endoperoxide shift and should be evaluated further, along with modalities to reduce oxidative stress among patients on CMD.


Agostoni, C. and W. Heird (2004). "Long chain polyunsaturated fatty acids in chronic childhood disorders: panacea, promising, or placebo." J Pediatr Gastroenterol Nutr 38(1): 2-3.


Zolfaghari, R. and A. C. Ross (2003). "Recent advances in molecular cloning of fatty acid desaturase genes and the regulation of their expression by dietary vitamin A and retinoic acid." Prostaglandins Leukot Essent Fatty Acids 68(2): 171-9.

            Vitamin A, as an essential micronutrient, is involved in higher animals in embryonic development and postnatal growth, reproduction and maintenance of normal skin, immunity and vision. Recently, studies in vivo and in cell lines have shown that vitamin A and its active metabolite, retinoic acid, regulate the expression of fatty acid desaturases including stearoyl-CoA desaturase and delta-5 desaturase. Whereas the former desaturase catalyzes the formation of monounsaturated from saturated fatty acids, the latter enzyme is involved in the desaturation pathway of dietary essential fatty acids for production of polyunsaturated fatty acids. The reaction products of these desaturases serve as critical regulators in a wide range of physiological processes which include fetal growth and development, reproduction, cell differentiation, immune and inflammatory responses.


Zeyda, M., A. B. Szekeres, et al. (2003). "Suppression of T cell signaling by polyunsaturated fatty acids: selectivity in inhibition of mitogen-activated protein kinase and nuclear factor activation." J Immunol 170(12): 6033-9.

            Polyunsaturated fatty acids (PUFAs) are known to suppress inflammatory and autoimmune responses and, therefore, clinical applications of PUFAs as immunomodulatory substances are extensively studied. PUFAs are known to inhibit T cell responses, but with respect to TCR/CD3-mediated signal transduction only a block in CD3-induced phospholipase Cgamma1/calcium signaling has been shown so far. In this study, we investigated PUFA-mediated changes in downstream T cell signal transduction. We show that among the mitogen-activated protein kinase families activation of c-Jun NH(2)-terminal kinase, but not phosphorylation of extracellular signal-regulated kinase-1/-2 or p38 is inhibited. CD3/CD28-induced activity of NF-AT was markedly reduced by PUFA treatment, while activation of other nuclear receptors (AP-1 and NF-kappaB) remained unaltered. Furthermore, IL-2 promoter activity, IL-2 and IL-13 mRNA levels, IL-2 secretion, and IL-2R alpha-chain expression were significantly diminished by PUFA treatment, whereas the expression of IFN-gamma, IL-4, IL-10, and CD69 remained essentially unaffected by PUFAs. In conclusion, PUFA treatment of T cells inhibits selectively c-Jun NH(2)-terminal kinase and NF-AT activation, resulting in diminished production of IL-2 and IL-13.


Zeitlin, L., E. Segev, et al. (2003). "Effects of long-term administration of N-3 polyunsaturated fatty acids (PUFA) and selective estrogen receptor modulator (SERM) derivatives in ovariectomized (OVX) mice." J Cell Biochem 90(2): 347-60.

            We studied the beneficial effects of dietary consumption of n-3 polyunsaturated fatty acids (PUFA) and two selective estrogen receptor modulator (SERM) derivatives (SERM-I and SERM-II) and their combined effect on serum lipids, skin dermis and adipose layers, bone marrow adipogenesis, and cytokine secretion in mice. Two different ovariectomized (OVX) models were studied: treatment began immediately post-OVX in one and 3 months post-OVX in the other. Our results showed that n-3 PUFA and both SERMs decreased triglyceride levels in the serum, and that SERMs also decreased serum cholesterol levels while n-3 PUFA had no similar effect. SERMs had no effect on IL-6, IL-1 beta, or IL-10 levels, but they decreased ex vivo tumor necrosis factor (TNF-alpha). N-3 PUFA decreased secretion of non-induced IL-6 and TNF-alpha from cultured BMC and IL-1 beta levels in vivo (i.e., in bone marrow plasma), but its main effect was a significant elevation in the secretion of IL-10, a known anti-inflammatory cytokine. OVX-induced B-lymphopoiesis was not affected by LY-139481 (SERM-I) while LY-353381 (SERM-II) exhibited an estrogen-antagonistic effect in sham and OVX mice and elevated the amount of B-cells in bone marrow. Fish oil consumption prevented the elevation in B-lymphopoiesis caused by OVX, but had no curative effect on established augmented B-lymphopoiesis. This activity could be mediated via the elevation of IL-10 which was shown to suppress B-lymphopoiesis. Both SERMs and n-3 PUFA inhibited the increase in adipose tissue thickness caused by OVX in mice. Our results showed that n-3 PUFA, could prevent some of the deleterious outcomes of estrogen deficiency that were not affected by SERMs. We observed no significant beneficial effects of the combined administration of SERM-I, SERM-II, and PUFA on the studied parameters.The exact mechanism by which polyunsaturated fatty acids exert their activities is still not clear, but peroxisome proliferator-activated receptors (PPARs) might be involved in processes which are modulated by n-3 PUFA.


Zeh, N., S. S. Rossi, et al. (2003). "The effect of extracorporeal albumin dialysis on plasma phospholipid fatty acids in patients with end-stage liver disease." Liver Int 23 Suppl 3: 34-8.

            The effect of extracorporeal albumin dialysis (ECAD) using the MARS device on plasma phospholipid fatty acids (PLFA) in patients with end-stage liver disease (ESLD) was examined. Phospholipids were isolated from plasma and the fatty acid (FA) composition of non-sphingomyelin PL determined using capillary gas chromatography (GC). Plasma samples were also obtained from six patients with ESLD undergoing ECAD and from five patients with similar ESLD who were not treated, as well as from non-fasting healthy subjects. PLFA were much lower [506 +/- 62 microg/mL (M +/- SD)] in patients with ESLD than in healthy subjects (2709 +/- 688 microg/mL). In addition, the proportion of n3 and n6 polyunsaturated FA was much lower in patients with ESLD (n3, 1.7 +/- 0.1%, n6, 19.6 +/- 1.4%) than in healthy controls (n3, 4.1 +/- 2.4%, n6, 31.9 +/- 6.2%) ECAD caused an immediate increase in PLFA, averaging 56% in all patients, but PLFA levels decreased some hours later after treatment. ECAD also caused a small increase in the proportion of n3 and n6 of PLFA. During the 5 days of the study, PLFA rose in both ECAD-treated and untreated patients, but the increase was significantly greater in ECAD treated patient. It is concluded that patients with ESLD have markedly decreased PLFA; these PLFA have a lower proportion of the polyunsaturated n3 and n6 FA with the result that the plasma level of these essential polyunsaturated PLFA is extremely low compared to that of healthy subjects. ECAD causes a transient increase in PLFA toward normal levels and also increases the proportion of n3 and n6 FA.


Zackova, M., E. Skobisova, et al. (2003). "Activating omega-6 polyunsaturated fatty acids and inhibitory purine nucleotides are high affinity ligands for novel mitochondrial uncoupling proteins UCP2 and UCP3." J Biol Chem 278(23): 20761-9.

            UCP2 (the lowest Km values: 20 and 29 microm, respectively) for omega-6 polyunsaturated FAs (PUFAs), all-cis-8,11,14-eicosatrienoic and all-cis-6,9,12-octadecatrienoic acids, which are also the most potent agonists of the nuclear PPARbeta receptor in the activation of UCP2 transcription. omega-3 PUFA, cis-5,8,11,14,17-eicosapentaenoic acid had lower affinity (Km, 50 microm), although as an omega-6 PUFA, arachidonic acid exhibited the same low affinity as lauric acid (Km, approximately 200 microm). These findings suggest a possible dual role of some PUFAs in activating both UCPn expression and uncoupling activity. UCP2 (UCP3)-dependent H+ translocation activated by all tested FAs was inhibited by purine nucleotides with apparent affinity to UCP2 (reciprocal Ki) decreasing in order: ADP > ATP approximately GTP > GDP >> AMP. Also [3H]GTP ([3H]ATP) binding to isolated Escherichia coli (Kd, approximately 5 microm) or yeast-expressed UCP2 (Kd, approximately 1.5 microm) or UCP3 exhibited high affinity, similar to UCP1. The estimated number of [3H]GTP high affinity (Kd, <0.4 microm) binding sites was (in pmol/mg of protein) 182 in lung mitochondria, 74 in kidney, 28 in skeletal muscle, and approximately 20 in liver mitochondria. We conclude that purine nucleotides must be the physiological inhibitors of UCPn-mediated uncoupling in vivo.


Yusufi, A. N., J. Cheng, et al. (2003). "Differential effects of low-dose docosahexaenoic acid and eicosapentaenoic acid on the regulation of mitogenic signaling pathways in mesangial cells." J Lab Clin Med 141(5): 318-29.

            Although dietary fish oil supplementation has been used to prevent the progression of kidney disease in patients with IgA nephropathy, relatively few studies provide a mechanistic rationale for its use. Using an antithymocyte (ATS) model of mesangial proliferative glomerulonephritis, we recently demonstrated that fish oil inhibits mesangial cell (MC) activation and proliferation, reduces proteinuria, and decreases histologic evidence of glomerular damage. We therefore sought to define potential mechanisms underlying the antiproliferative effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the predominant omega-3 polyunsaturated fatty acids found in fish oil, in cultured MC. DHA and EPA were administered to MC as bovine serum albumin fatty-acid complexes. Low-dose (10-50 micromol/L) DHA, but not EPA, inhibited basal and epidermal growth factor (EGF)-stimulated [(3)H]-thymidine incorporation in MCs. At higher doses (100 micromol/L), EPA and DHA were equally effective in suppressing basal and EGF-stimulated MC mitogenesis. Low-dose DHA, but not EPA, decreased ERK activation by 30% (P <.01), as assessed with Western-blot analysis using phosphospecific antibodies. JNK activity was increased by low-dose DHA but not by EPA. p38 activity was not significantly altered by DHA or EPA. Cyclin E activity, as assessed with a histone H1 kinase assay, was inhibited by low-dose DHA but not by EPA. DHA increased expression of the cell cycle inhibitor p21 but not p27; EPA had no effect on p21 or p27. We propose that the differential effect of low-dose DHA vs EPA in suppressing MC mitogenesis is related to down-regulation of ERK and cyclin E activity and to induction of p21.


Yuri, T., N. Danbara, et al. (2003). "Dietary docosahexaenoic acid suppresses N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats more effectively than eicosapentaenoic acid." Nutr Cancer 45(2): 211-7.

            We compared the effects of identical amounts but different proportions of dietary n-3 polyunsaturated fatty acids (PUFAs) on N-methyl-N-nitrosourea (MNU)-induced mammary cancer in a rat model. The ability of dietary docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to suppress mammary cancer was evaluated. Female Sprague-Dawley rats were randomly assigned to three groups and maintained on diets containing 10% fatty acid consisting of EPA, a 1:1 mixture of EPA-plus-DHA, or DHA. The experimental diet was started after administration of MNU at 49 days of age, and the rats were maintained on the respective diets until the largest mammary tumor reached >1 cm in diameter or until the end of the study period (20 wk after MNU). All histologically detected mammary carcinomas were evaluated, irrespective of size. The DHA diet was associated with significant suppression of the carcinogenic effect of MNU compared with the EPA and EPA-plus-DHA diets: tumor incidence decreased to 23% (3/13) compared with 73% (11/15) and 65% (12/17) (P < 0.01 and P < 0.05, respectively); tumor multiplicity decreased to 0.23 compared with 1.67 and 1.59 (P < 0.01 and P < 0.05, respectively). There was no significant difference in tumor latency among the DHA, EPA, and EPA-plus-DHA groups (119, 105, and 117 days, respectively). Over 20 wk, the fatty acid composition of serum and mammary fat tissue reflected differences in the dietary n-3 PUFAs. Although DHA suppressed MNU-induced mammary carcinogenesis more effectively than EPA, generalized steatosis including mammary fat tissue appeared in all three groups.


Young, J. F., K. Rosenvold, et al. (2003). "Significance of preslaughter stress and different tissue PUFA levels on the oxidative status and stability of porcine muscle and meat." J Agric Food Chem 51(23): 6877-81.

            Polyunsaturated fatty acids (PUFAs) and exercise-induced stress are known to increase the oxidative susceptibility of lipids in muscle tissue. In contrast, antioxidative enzymes, e.g., catalase, superoxide dismutase, and glutathione peroxidase, are known to help sustain the delicate oxidative balance in biological tissue upon the application of stressors. The present study investigates the combined effect of different diet-induced muscle PUFA contents and preslaughter stress on the activity of antioxidative muscle enzymes and the oxidative stability of cooked meat. An increased content of unsaturated fatty acids in the tissue led to a decreased activity of lactate dehydrogenase in the plasma, indicating increased cell integrity. Catalase activity in the muscle tissue increased with increasing PUFA levels. However, this upregulation in antioxidative status of the muscle could not counteract the subsequent development of accelerated lipid oxidation in cooked meat as measured in terms of thiobarbituric acid reactive substances. Moreover, preslaughter stress induced increasing oxidative changes with elevated PUFA levels in the muscle tissue.


Yoshida, H., H. Soh, et al. (2003). "Beneficial effects of n-9 eicosatrienoic acid on experimental bowel lesions." Surg Today 33(8): 600-5.

            PURPOSE: Dietary fortification of n-9 polyunsaturated fatty acids (PUFA) or 5,8,11-eicosatrienoic acid (ETrA) as well as n-3 PUFA might contribute to the suppression of leukotriene B4 (LTB4) synthesis and thereby reduce inflammatory bowel lesions. As a result, the effect of an ETrA-enriched diet on experimental bowel lesions was examined in this study. METHODS: In Expt. 1, rats were freely fed either an ETrA-enriched or a standard diet. After 7 days of feeding, acute bowel lesions were induced by the subcutaneous injection of 10 mg/kg indomethacin. In Expt. 2, chronic bowel lesions were made by performing subcutaneous injections of 7.5 mg/kg indomethacin twice. After the first injection, the rats were freely fed either an ETrA-enriched or a standard diet for 7 days. RESULTS: In both experiments, the rats fed an ETrA-enriched diet showed increased levels of ETrA in the plasma and intestinal mucosa, and a decreased inflammation score. However, there was no significant decrease in plasma and intestinal mucosal LTB4 in the ETrA-enriched diet-fed rats. CONCLUSION: These results suggest that the dietary supplementation of ETrA may have both prophylactic and therapeutic effects on experimentally produced bowel lesions. Further investigations are necessary to clarify the effects of ETrA on bowel lesions and its mechanisms.


Yoshida, S. and H. Yoshida (2003). "Nondestructive analyses of unsaturated fatty acid species in dietary oils by attenuated total reflectance with Fourier transform IR spectroscopy." Biopolymers 70(4): 604-13.

            The aim of this study was to develop a nondestructive method to quantitate relative amounts of n-3 and n-6 polyunsaturated fatty acid (PUFA) species in vegetable oils and oil seeds using Fourier transform IR spectroscopy (FTIR). The alkene Cbond;H stretching vibrations of unsaturated fatty acids in oils showed IR absorption bands with various peak positions and intensities at around 3010 cm(-1), depending on the extent of unsaturation and PUFA species. With the aid of partial least-squares regression analysis, the FTIR measurement could practically predict the content of each PUFA species in the oil to be tested. A calculation method was also presented to directly find PUFA species in oils from the FTIR spectra. This technique was applied to dried soybean seeds to demonstrate a nonhomogenous distribution of saturated fatty acids and PUFAs, as well as glycans, in soybean cross sections.


Yokoyama, M. and H. Origasa (2003). "Effects of eicosapentaenoic acid on cardiovascular events in Japanese patients with hypercholesterolemia: rationale, design, and baseline characteristics of the Japan EPA Lipid Intervention Study (JELIS)." Am Heart J 146(4): 613-20.

            HYPOTHESIS: The principle aim of the current study is to test the hypothesis that the long-term use of highly purified EPA (eicosapentaenoic acid: 1800 mg/day), in addition to HMG-CoA reductase inhibitor, is effective in preventing cardiovascular events in Japanese patients with hypercholesterolemia. BACKGROUND: Epidemiological and clinical evidence suggest that intake of long-chain polyunsaturated n-3 fatty acids (PUFAs), which are abundant in fish, might have a significant role in the prevention of coronary artery disease, as marine PUFAs have multiple biological functions through lipid-dependent and lipid-independent mechanisms. METHODS: The Japan EPA Lipid Intervention Study (JELIS) is a prospective, randomized, open-label, blinded end point trial including both primary and secondary prevention strata, with a maximum follow-up of 5 years. Its main purpose is to examine the clinical effectiveness of EPA oil given as an additional treatment to patients taking HMG-CoA reductase inhibitors for hypercholesterolemia. A primary end point is major coronary events: sudden cardiac death, fatal and nonfatal myocardial infarction, and unstable angina pectoris including hospitalization for documented ischemic episodes, and events of angioplasty/stenting or coronary artery bypass grafting. Secondary end points include all-cause mortality, stroke, peripheral artery disease, and cancer. Baseline study composition comprises 15,000 participants (4204 men and 10,796 women) in the primary prevention stratum and 3645 (1656 men and 1989 women) in the secondary stratum. The minimum age is 40 years for men, women are required to be postmenopausal, and all patients must be < or =75 years of age. The mean age of participants is 61 years, and 69% are female. The schedule for plasma fatty acid composition measurement is as follows: at baseline, at 6 month, and yearly thereafter. The mean baseline total and low-density lipoprotein cholesterol levels were 275 mg/dL (7.1 mmol/L) and 180 mg/dL (4.6 mmol/L). RESULTS: Results are expected in 2005. CONCLUSION: JELIS is a large clinical trial that will evaluate whether EPA can make an additional improvement in mortality and morbidity of coronary artery disease beyond that of HMG-CoA reductase inhibitor treatment.


Yin, H. and N. A. Porter (2003). "Specificity of the ferrous oxidation of xylenol orange assay: analysis of autoxidation products of cholesteryl arachidonate." Anal Biochem 313(2): 319-26.

            Autoxidation of polyunsaturated fatty acids and esters leads to a complex mixture containing hydroperoxides and cyclic peroxides. The oxidation mixture of cholesteryl arachidonate, which has been characterized by a variety of mass spectrometry techniques, was subject to analysis by conventional thiobarbituric acid-reactive substance (TBARS) and ferrous oxidation in xylenol orange (FOX) assays. Our results indicate that the FOX assay is not specific for hydroperoxides. Cyclic peroxides, such as monocyclic peroxides and serial-cyclic peroxides, give a positive FOX response even after triphenylphosphine reduction. We suggest that bicyclic endoperoxides are the major TBARS active compounds present in cholesteryl arachidonate oxidation mixtures. These compounds give a positive FOX assay before reaction with triphenylphosphine but negative TBARS and FOX assays after this reaction. Caution should be exercised when the FOX assay is used to analyze highly oxidized lipids, especially arachidonyl-containing lipids.


Yatsuya, H., A. Ohwaki, et al. (2003). "Reproducibility and validity of a simple checklist-type questionnaire for food intake and dietary behavior." J Epidemiol 13(5): 235-45.

            BACKGROUND: A simple, reliable, and valid food questionnaire is needed in clinical dietary assessments, community health education, and multi-purpose epidemiologic studies to obtain a crude measure of dietary intake. METHODS: To assess the validity and reproducibility of a simple 4-point scale food intake and behavior checklist, it was compared to two 3-day weighed dietary records. The FBC was administered to 47 students of a dietician course and their parents (n = 94) over a 9-month interval to assess the reproducibility. The mean intakes of selected food groups assessed by the two dietary records completed between food intake and behavior checklists were compared to the responses to the food intake and behavior checklist to assess its validity. RESULTS: The kappa statistics for reproducibility ranged from 0.25 for confectionaries to 0.63 for a preference for fatty foods (median, 0.39). There was a reasonable level of correlation between the dietary record and the food intake and behavior checklist in the intake of eggs, milk, and fruits (r = 0.53, 0.56, and 0.50, respectively). There was a weaker but still significant correlation in the intake of vegetables, and alcohol (r = 0.31 and 0.45, respectively). No significant correlation was observed in the intake of meat, fish, confectionaries, and soft drinks. However, those who reported consuming mainly fish rather than meat were found to eat significantly less meat and animal fat. Similarly, those who did not prefer fatty foods consumed significantly less meat, animal fat, and polyunsaturated fatty acids. CONCLUSIONS: This simple food checklist was useful in collecting data on egg, milk, and fruit consumption. Assessing intake frequency of vegetables, meat or fish with the FBC may be useful in screening high- or low-intake individuals.


Yaqoob, P. and P. C. Calder (2003). "N-3 polyunsaturated fatty acids and inflammation in the arterial wall." Eur J Med Res 8(8): 337-54.

            Atherosclerosis, leading to cardiovascular disease, is a chronic condition involving a strong inflammatory component. There is evidence that the n-3 polyunsaturated fatty acids (PUFA) present in oily fish and fish oils protect against cardiovascular disease. While these fatty acids have well-recognised effects on plasma triacylglycerol concentrations, it is likely that they exert beneficial effects through other mechanisms in addition. A large body of evidence suggests that the n-3 PUFA have anti-inflammatory properties, some of which may be manifested in the arterial wall, either directly or indirectly, to modulate the progression of atherosclerosis. This review critically evaluates the evidence for the anti-inflammatory effects of the n-3 PUFA in cells and on pathways which have a direct influence on atherogenesis in the arterial wall.


Yao, J. K., C. G. Sistilli, et al. (2003). "Membrane polyunsaturated fatty acids and CSF cytokines in patients with schizophrenia." Prostaglandins Leukot Essent Fatty Acids 69(6): 429-36.

            Findings to date provide evidence that altered membrane structure and function are present in patients with either first-episode or chronic schizophrenia, suggesting defects in phospholipid metabolism and cell signaling in schizophrenia. The purpose of this investigation is to test whether decreased membrane polyunsaturated fatty acids (PUFAs) were associated with an increased secretion of proinflammatory cytokines. Thus, we measured interleukin 6 (IL-6) and interleukin 10 (IL-10) in cerebrospinal fluid (CSF) of patients with chronic schizophrenia as well as PUFAs of red blood cell (RBC) membranes from the same individuals. A significant and inverse correlation was found between CSF IL-6 (not IL-10) and RBC membrane PUFAs levels in both haloperidol-treated and medication-free patients with schizophrenia. Specifically, such an association was found in the n-6 (18:2, 20:4, and 22:4) and, to a lesser extent, the n-3 fatty acids. Taken together, the present findings suggest that decreased membrane PUFAs may be related to an immune disturbance in schizophrenia, possibly resulting from an increased phospholipase A2 activity mediated through the proinflammatory cytokines.


Yamagata, K., M. Tagami, et al. (2003). "Polyunsaturated fatty acids induce tight junctions to form in brain capillary endothelial cells." Neuroscience 116(3): 649-56.

            Tight junctions create a rate-limiting barrier to the diffusion of solutes between vertebrate epithelial cells and endothelial cells. They are also controlled within individual cells by a variety of physiologically relevant signals. We investigated the effects of polyunsaturated fatty acids on the formation of tight junctions in brain capillary endothelial cells, monitoring the transepithelial electrical resistance, and analyzed the expression of occludin messenger RNA. Brain-capillary endothelial cells were grown to confluence on filters and exposed to eicosapentaenoic acids, gamma linolenic acid and linoleic acid. Transepithelial electrical resistance was determined with voltage-measuring electrodes. The messenger RNA expression of occludin was quantitated by real-time quantitative reverse transcriptase-polymerase chain reaction. The basal resistance across monolayers of porcine brain capillary endothelial cells was 83+/-8.1 Omega cm(2). Cells cultured in eicosapentaenoic acids and gamma linolenic acid, but not linolenic acid, displayed a 2.7-fold increase in transepithelial electrical resistance at 10 microM in brain capillary endothelial cells. The expression level of occludin messenger RNA increased markedly immediately after the exposure to eicosapentaenoic acids or gamma linolenic acid. Following an 8 h exposure to exogenous eicosapentaenoic acids or gamma linolenic acid, occludin messenger RNA levels were significantly increased. In addition, the rise in transepithelial electrical resistance induced by eicosapentaenoic acids and gamma linolenic acid was markedly inhibited by the tyrosine kinase inhibitors genistein and PP2 and protein kinase C inhibitor, calphostin C. In contrast, the rise in transepithelial electrical resistance induced by eicosapentaenoic acids and gamma linolenic acid was not inhibited by the PI 3-kinase inhibitor, LY294002.We conclude that eicosapentaenoic acids and gamma linolenic acid increased the transepithelial electrical resistance and the expression of occludin messenger RNA in brain capillary endothelial cells. This gamma linolenic acid and eicosapentaenoic acid induced assembly of tight junction is likely to be regulated by protein kinase C and tyrosine kinase activity.


Yakimov, M. M., L. Giuliano, et al. (2003). "Oleispira antarctica gen. nov., sp. nov., a novel hydrocarbonoclastic marine bacterium isolated from Antarctic coastal sea water." Int J Syst Evol Microbiol 53(Pt 3): 779-85.

            The taxonomic characteristics of two bacterial strains, RB-8(T) and RB-9, isolated from hydrocarbon-degrading enrichment cultures obtained from Antarctic coastal marine environments (Rod Bay, Ross Sea), were determined. These bacteria were psychrophilic, aerobic and Gram-negative with polar flagella. Growth was not observed in the absence of NaCl, occurred only at concentrations of Na+ above 20 mM and was optimal at an NaCl concentration of 3-5% (w/v). The major cellular fatty acids were monounsaturated straight-chain fatty acids. The strains were able to synthesize the polyunsaturated fatty acid eicosapentaenoic acid (20: 5omega3) at low temperatures. The DNA G + C contents were 41-42 mol%. The strains formed a distinct phyletic line within the gamma-Proteobacteria, with less than 89.6% sequence identity to their closest relatives within the Bacteria with validly published names. Both isolates exhibited a restricted substrate profile, with a preference for aliphatic hydrocarbons, that is typical of marine hydrocarbonoclastic micro-organisms such as Alcanivorax, Marinobacter and Oleiphilus. On the basis of ecophysiological properties, G + C content, 16S rRNA gene sequences and fatty acid composition, a novel genus and species within the gamma-Proteobacteria are proposed, Oleispira antarctica gen. nov., sp. nov.; strain RB-8(T) (= DSM 14852(T) = LMG 21398(T)) is the type strain.


Xian, M., J. Nie, et al. (2003). "Production of gamma-linolenic acid by disrupted mycelia of Mortierella isabellina." Lett Appl Microbiol 36(3): 182-5.

            AIMS: To optimize the production of linolenic acid by disrupted mycelia of Mortierella isabellina. METHODS AND RESULTS: Effects of incubation conditions such as incubation time, pH of reaction mixture, concentration of Mg2+ or malate and incubation temperature on production of linolenic acid were studied. The production of gamma-linolenic acid reached 224 mg g-1 dry cells when the reaction mixture was composed of 1.0 g (dry mycelial mass) of disrupted mycelia of M. isabellina, 50 ml (50 mmol l(-1)) potassium phosphate buffer supplemented with 0.312 mmol l(-1) of Mg2+ and 10 mmol l(-1) of malate, pH 7.0 and incubated at 5 degrees C for 1 day. CONCLUSIONS: Incubation temperature, concentration of Mg2+ and malate showed major effects on the increased linolenic acid production. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlights conditions for increasing gamma-linolenic acid production by cell-free mycelia of M. isabellina and an insight into rapidly gaining high production of polyunsaturated fatty acids.


Wood, L. G., D. A. Fitzgerald, et al. (2003). "Hypothesis: vitamin E complements polyunsaturated fatty acids in essential fatty acid deficiency in cystic fibrosis." J Am Coll Nutr 22(4): 253-7.

            While several studies have demonstrated essential fatty acid (EFA) deficiency in plasma and tissue lipids of cystic fibrosis (CF) patients, the reasons for this deficiency are not well established. It is believed that reduced EFA intake, malabsorption of fat, altered desaturase/lipase activity and defective cystic fibrosis transmembrane conductance regulator (CFTR) altering utilisation of EFA in epithelial cells contribute to the development of EFA deficiency in CF. It is likely that increased metabolism of arachidonic acid to eicosanoids such as leukotrienes, thromboxane and prostaglandins may also be a contributing factor. Evidence is presented that elevated oxidative damage to EFA and impaired antioxidant defences, in particular vitamin E, may contribute to the development of EFA deficiency in CF. Furthermore, antioxidant supplementation in CF may improve EFA status.


Wolfram, G. (2003). "Dietary fatty acids and coronary heart disease." Eur J Med Res 8(8): 321-4.

            Epidemiological studies have confirmed a strong association between fat intake, especially saturated and trans fatty acids, plasma cholesterol levels and rate of coronary heart disease (CHD) mortality. Meanwhile it is clear, that early atherosclerosis is largely preventable by modifying nutritional behaviour and lifestyle. There is clear evidence that a diet moderate in total fat (25-35 % energy) is superior to extremes in dietary fat. Because fat is energy dense moderation in fat intake is also essential for weight control. Saturated fatty acids are very potent in increasing LDL-cholesterol concentration in plasma a dangerous risk factor for early CHD. Unsaturated fatty acids have numerous beneficial health effects. The results of prospective cohort studies fit well to the experimental experience of the antihypercholesterolemic action of Omega-6 fatty acids and the antithrombotic, vasodilatory and antiarrhythmic properties of Omega-3 fatty acids, while the optimistic rating of Omega-9 fatty acids is less supported by epidemiologic studies. The results of prospective cohort studies are confirmed by intervention trials revealing that saturated fatty acids enhance early development of CHD whereas polyunsaturated fatty acids, especially of the Omega-3 type, significantly preserve from CHD. In context with a prudent diet pattern favourable dietary fatty acid composition offers the best chance for a reduced risk of CHD.


Wijendran, V., A. Pronczuk, et al. (2003). "Dietary trans-18:1 raises plasma triglycerides and VLDL cholesterol when replacing either 16:0 or 18:0 in gerbils." J Nutr Biochem 14(10): 584-90.

            To compare the relative impact of trans-18:1 with the two main dietary saturated fatty acids it replaces, plasma lipid response was assessed in Mongolian gerbils fed diets rich in 16:0 (24%en),18:0 (10%en), or trans-18:1 (4 or 6%en). The diets were designed such that the 18:0-rich diet substituted 7%en as 18:0 for 16:0, whereas 4%en and 6%en from trans-18:1 was substituted for 16:0 in the two trans diets. The control group was fed a diet formulated according to the fatty acid balance of American Heart Association (AHA), but provided 40%en as fat. Gerbils (n = 10 per dietary group) were fed one of the five diets for 8 weeks. The control diet, with 4 times the polyunsaturated fatty acids (PUFA) content and a P:S ratio about 10 times greater than the test diets, resulted in the lowest plasma TC, LDL cholesterol (LDL-C) and VLDL cholesterol (VLDL-C). Among the test diets, plasma TC and TG were lowest with the 18:0-rich diet. TC in gerbils fed the 16:0-rich diet and 4%en-trans were 20% higher than the 18:0-rich diet, while the 6%en-trans diet was 35% higher. VLDL-C was significantly higher in the 6%en-trans diet compared to all other groups at 8 weeks. Both trans fatty acid diets elevated plasma TG approximately 2- and 3-fold, respectively, compared to the 16:0-rich and 18:0-rich diets at 8 weeks. Further, plasma TG continued to rise over time with trans fatty acids compared to 16:0 or 18:0. Thus, in the fatty acid-sensitive gerbil, impaired TG metabolism represents a major aspect of the hyperlipemia caused by trans fatty acid substitution for major saturated fatty acids.


Wiesner, R., H. Suzuki, et al. (2003). "Suicidal inactivation of the rabbit 15-lipoxygenase by 15S-HpETE is paralleled by covalent modification of active site peptides." Free Radic Biol Med 34(3): 304-15.

            Lipoxygenases (LOXs) are multifunctional enzymes that catalyze the oxygenation of polyunsaturated fatty acids to hydroperoxy derivatives; they also convert hydroperoxy fatty acids to epoxy leukotrienes and other secondary products. LOXs undergo suicidal inactivation but the mechanism of this process is still unclear. We investigated the mechanism of suicidal inactivation of the rabbit 15-lipoxygenase by [1-(14)C]-(15S,5Z,8Z,11Z,13E)-15-hydroperoxyeicosa-5,8,11,13-tetraenoic acid (15-HpETE) and observed covalent modification of the enzyme protein. In contrast, nonlipoxygenase proteins (bovine serum albumin and human gamma-globulin) were not significantly modified. Under the conditions of complete enzyme inactivation we found that 1.3 +/- 0.2 moles (n = 10) of inactivator were bound per mole lipoxygenase, and this value did depend neither on the enzyme/inactivator ratio nor on the duration of the inactivation period. Covalent modification required active enzyme protein and proceeded to a similar extent under aerobic and anaerobic conditions. In contrast, [1-(14)C]-(15S,5Z,8Z,11Z,13E)-15-hydroxyeicosa-5,8,11,13-tetraenoic acid (15-HETE), which is no substrate for epoxy-leukotriene formation, did not inactivate the enzyme and protein labeling was minimal. Separation of proteolytic cleavage peptides (Lys-C endoproteinase digestion) by tricine SDS-PAGE and isoelectric focusing in connection with N-terminal amino acid sequencing revealed covalent modification of several active site peptides. These data suggest that 15-lipoxygenase-catalyzed conversion of (15S,5Z,8Z,11Z,13E)-15-hydroperoxyeicosa-5,8,11,13-tetraenoic acid to 14,15-epoxy-leukotriene leads to the formation of reactive intermediate(s), which are covalently linked to the active site. Therefore, this protein modification contributes to suicidal inactivation.


Wiedemann, M., A. Kontush, et al. (2003). "Neonatal blood plasma is less susceptible to oxidation than adult plasma owing to its higher content of bilirubin and lower content of oxidizable Fatty acids." Pediatr Res 53(5): 843-9.

            Newborn infants are susceptible to a range of problems attributed to excessive production of free radicals. Because of a higher content of antioxidants, above all bilirubin, and a lower content of oxidizable lipids, newborn plasma should be better protected against oxidation than adult plasma. To test this hypothesis, we measured the susceptibility of plasma to in vitro oxidation in microsamples (7 microL) from 57 healthy newborns and 18 adults. Heparin plasma was diluted 150-fold and oxidized by 50 microM Cu2+. Oxidation was monitored as an increase in sample absorbance at 234 nm. Plasma oxidizability was found to be significantly lower in newborns than in adults. Accordingly, the level of bilirubin, an important antioxidant, was significantly higher, and the level of polyunsaturated fatty acids, a major substrate of lipid peroxidation, was significantly lower in newborn plasma. In addition, plasma oxidizability correlated positively with the level of polyunsaturated fatty acids and negatively with that of bilirubin. These data indicate that plasma is better protected against oxidative stress in newborns than in adults, owing to its higher content of antioxidants like bilirubin and its lower content of oxidizable lipids.


Whitehouse, A. S., J. Khal, et al. (2003). "Induction of protein catabolism in myotubes by 15(S)-hydroxyeicosatetraenoic acid through increased expression of the ubiquitin-proteasome pathway." Br J Cancer 89(4): 737-45.

            The potential role of 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) as an intracellular signal for increased protein catabolism and induction of the expression of key components of the ubiquitin-proteasome proteolytic pathway induced by a tumour cachectic factor, proteolysis-inducing factor has been studied in murine C(2)C(12) myotubes. 15(S)-HETE induced protein degradation in these cells with a maximal effect at concentrations between 78 and 312 nM. The effect was attenuated by the polyunsaturated fatty acid, eicosapentaenoic acid (EPA). There was an increase in 'chymotrypsin-like' enzyme activity, the predominant proteolytic activity of the proteasome, in the same concentration range as that inducing total protein degradation, and this effect was also attenuated by EPA. 15(S)-hydroxyeicosatetraenoic acid also increased maximal expression of mRNA for proteasome subunits C2 and C5, as well as the ubiquitin-conjugating enzyme, E2(14k), after 4 h incubation, as determined by quantitative competitive RT-PCR. The concentrations of 15-HETE affecting gene expression were the same as those inducing protein degradation. Western blotting of cellular supernatants of myotubes treated with 15(S)-HETE for 24 h showed increased expression of p42, an ATPase subunit of the regulatory complex at similar concentrations, as well as a decrease in expression of myosin in the same concentration range. 15(S)-hydroxyeicosatetraenoic acid activated binding of nuclear factor-kappaB (NF-kappaB) in the myotube nucleus and stimulated degradation of I-kappaBalpha. The effect on the NF-kappaB/I-kappaBalpha system was attenuated by EPA. In addition, the NF-kappaB inhibitor peptide SN50 attenuated the increased chymotrypsin-like enzyme activity in the presence of 15(S)-HETE. These results suggest that 15(S)-HETE induces degradation of myofibrillar proteins in differentiated myotubes through an induction of an increased expression of the regulatory components of the ubiquitin-proteasome proteolytic pathway possibly through the intervention of the nuclear transcription factor NF-kappaB, and that this process is inhibited by EPA.


Westhuyzen, J., D. Saltissi, et al. (2003). "Oxidative stress and erythrocyte integrity in end-stage renal failure patients hemodialysed using a vitamin E-modified membrane." Ann Clin Lab Sci 33(1): 3-10.

            Oxidative stress has been implicated in a range of disease states, including end-stage renal failure treated with hemodialysis. Hemodialysis with vitamin E-modified membranes reduces lipid peroxidation, but the effect on erythrocyte integrity has not been determined. This study compared antioxidant defense parameters and the resistance of erythrocytes to free radical-mediated hemolysis in patients dialysed with cellulose acetate membranes at baseline and with a vitamin E-modified membrane (Excebrane Clirans; Terumo Corporation) for 13 wk. Resistance of erythrocytes to free radical attack was assessed in vitro using the peroxyl hemolysis test. The time to 50% hemolysis (T50%) increased significantly during the first 6 wk of Excebrane use (p < 0.05), but this parameter returned to baseline by 13 wk. Glutathione concentration and erythrocyte superoxide dismutase activity were unchanged during the study, but glutathione peroxidase activity increased from low levels at baseline and became significantly higher at 6 and 13 wk (p < 0.001). Total erythrocyte polyunsaturated fatty acid content and C18:2 level increased (p < 0.001) and saturated fatty acids (total, C16:0, C18:0, C22:0 and C24:0) decreased (p < 0.03). Total monounsaturated fatty acid content was unchanged. The increased resistance of erythrocytes to hemolysis, the increased glutathione peroxidase activity, and the increased degree of unsaturation of fatty acids in the erythrocyte membrane are compatible with a reduction of oxidative stress during hemodialysis with vitamin E-modified membranes.


Werner, A., R. Havinga, et al. (2003). "Treatment of essential fatty acid deficiency with dietary triglycerides or phospholipids in a murine model of extrahepatic cholestasis." Am J Physiol Gastrointest Liver Physiol.

            Background: Essential fatty acid (EFA) deficiency during cholestasis is mainly due to malabsorption of dietary EFA (23). Theoretically, dietary phospholipids (PL) may have a higher bioavailability than dietary triglycerides (TG) during cholestasis. We developed murine models for EFA deficiency with and without extrahepatic cholestasis, and compared the efficacy of oral supplementation of EFA as PL or as TG. Methods: EFA deficiency was induced in mice by feeding a high-fat EFA-deficient (EFAD) diet. After three weeks on this diet, bile duct ligation (BDL) was performed in a subgroup of mice to establish extrahepatic cholestasis. Cholestatic and non-cholestatic EFA-deficient mice continued on the EFAD diet (controls), or were supplemented for three weeks with EFA-rich TG or EFA-rich PL. Fatty acid composition was determined in plasma, erythrocytes, liver and brain. Results: After four weeks of EFAD diet, induction of EFA deficiency was confirmed by a six-fold increased triene/tetraene ratio (T/T-ratio) in erythrocytes of non-cholestatic and cholestatic mice (p<0.001). EFA-rich TG and EFA-rich PL were equally effective in preventing further increase of the erythrocyte T/T-ratio, which was observed in cholestatic and non-cholestatic non-supplemented mice (12- and 16-fold the initial value, respectively). In cholestatic mice, EFA-rich PL was superior to EFA-rich TG in decreasing T/T-ratios of liver triglycerides and phospholipids (each p<0.05), and in increasing brain phospholipid concentrations of the long-chain polyunsaturated fatty acids (LCPUFA) docosahexaenoic acid and arachidonic acid (each p<0.05). Conclusions: Oral EFA supplementation in the form of PL is more effective than in the form of TG in increasing LCPUFA concentrations in liver and brain of cholestatic EFA-deficient mice.


Wen, B., E. Deutsch, et al. (2003). "n-3 polyunsaturated fatty acids decrease mucosal/epidermal reactions and enhance antitumour effect of ionising radiation with inhibition of tumour angiogenesis." Br J Cancer 89(6): 1102-7.

            The purpose of this study was to evaluate the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on normal tissue (lip mucosa) and tumour growth when combined with ionising radiation. The oral region (snout) of C57 black mice was irradiated with 16.5 Gy and n-3 PUFAs (100 microl) were injected intravenously for 2 weeks. After exposure to irradiation, the degree and duration of the acute reactions decreased significantly when mice were treated with n-3 PUFAs as compared to the control group. Interestingly, the range of the reactions in the n-3 PUFAs-treated group compared favourably to the group receiving amifostine (27.5 mg/kg i.v.). the effect of n-3 PUFAs was further evaluated in HEP-2 human carcinoma xenograft transplanted in nude mice. An inhibition of tumour growth was observed when mice were treated with n-3 PUFAs alone and this effect was maximal when combined with irradiation. Similar results were obtained using eicosapentaenoic acid. The effect of n-3 PUFAs was associated with inhibition of angiogenesis and tumour proliferation, and significantly decreased expression of cyclooxygenase-2. In conclusion, n-3 PUFAs administration decrease mucosal response, while moderately enhancing the antitumour effect of irradiation. The magnitude of the differential effect suggests that n-3 PUFAs need to be further investigated in the clinic.


Wen, Z. Y. and F. Chen (2003). "Heterotrophic production of eicosapentaenoic acid by microalgae." Biotechnol Adv 21(4): 273-94.

            Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid that plays an important role in the regulation of biological functions and prevention and treatment of a number of human diseases such as heart and inflammatory diseases. As fish oil fails to meet the increasing demand for purified EPA, alternative sources are being sought. Microalgae contain large quantities of high-quality EPA and they are considered a potential source of this important fatty acid. Some microalgae can be grown heterotrophically on cheap organic substrate without light. This mode of cultivation can be well controlled and provides the possibility to maximize EPA production on a large scale. Numerous strategies have been investigated for commercial production of EPA by microalgae. These include screening of high EPA-yielding microalgal strains, improvement of strains by genetic manipulation, optimization of culture conditions, and development of efficient cultivation systems. This paper reviews recent advances in heterotrophic production of EPA by microalgae with an emphasis on the use of diatoms as producing organisms.


Weber, L. W., M. Boll, et al. (2003). "Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model." Crit Rev Toxicol 33(2): 105-36.

            The use of many halogenated alkanes such as carbon tetrachloride (CCl4), chloroform (CHCl3) or iodoform (CHI3), has been banned or severely restricted because of their distinct toxicity. Yet CCl4 continues to provide an important service today as a model substance to elucidate the mechanisms of action of hepatotoxic effects such as fatty degeneration, fibrosis, hepatocellular death, and carcinogenicity. In a matter of dose,exposure time, presence of potentiating agents, or age of the affected organism, regeneration can take place and lead to full recovery from liver damage. CCl4 is activated by cytochrome (CYP)2E1, CYP2B1 or CYP2B2, and possibly CYP3A, to form the trichloromethyl radical, CCl3*. This radical can bind to cellular molecules (nucleic acid, protein, lipid), impairing crucial cellular processes such as lipid metabolism, with the potential outcome of fatty degeneration (steatosis). Adduct formation between CCl3* and DNA is thought to function as initiator of hepatic cancer. This radical can also react with oxygen to form the trichloromethylperoxy radical CCl3OO*, a highly reactive species. CCl3OO* initiates the chain reaction of lipid peroxidation, which attacks and destroys polyunsaturated fatty acids, in particular those associated with phospholipids. This affects the permeabilities of mitochondrial, endoplasmic reticulum, and plasma membranes, resulting in the loss of cellular calcium sequestration and homeostasis, which can contribute heavily to subsequent cell damage. Among the degradation products of fatty acids are reactive aldehydes, especially 4-hydroxynonenal, which bind easily to functional groups of proteins and inhibit important enzyme activities. CCl4 intoxication also leads to hypomethylation of cellular components; in the case of RNA the outcome is thought to be inhibition of protein synthesis, in the case of phospholipids it plays a role in the inhibition of lipoprotein secretion. None of these processes per se is considered the ultimate cause of CCl4-induced cell death; it is by cooperation that they achieve a fatal outcome, provided the toxicant acts in a high single dose, or over longer periods of time at low doses. At the molecular level CCl4 activates tumor necrosis factor (TNF)alpha, nitric oxide (NO), and transforming growth factors (TGF)-alpha and -beta in the cell, processes that appear to direct the cell primarily toward (self-)destruction or fibrosis. TNFalpha pushes toward apoptosis, whereas the TGFs appear to direct toward fibrosis. Interleukin (IL)-6, although induced by TNFalpha, has a clearly antiapoptotic effect, and IL-10 also counteracts TNFalpha action. Thus, both interleukins have the potential to initiate recovery of the CCl4-damaged hepatocyte. Several of the above-mentioned toxication processes can be specifically interrupted with the use of antioxidants and mitogens, respectively, by restoring cellular methylation, or by preserving calcium sequestration. Chemicals that induce cytochromes that metabolize CCl4, or delay tissue regeneration when co-administered with CCl4 will potentiate its toxicity thoroughly, while appropriate CYP450 inhibitors will alleviate much of the toxicity. Oxygen partial pressure can also direct the course of CCl4 hepatotoxicity. Pressures between 5 and 35 mmHg favor lipid peroxidation, whereas absence of oxygen, as well as a partial pressure above 100 mmHg, both prevent lipid peroxidation entirely. Consequently, the location of CCl4-induced damage mirrors the oxygen gradient across the liver lobule. Mixed halogenated methanes and ethanes, found as so-called disinfection byproducts at low concentration in drinking water, elicit symptoms of toxicity very similar to carbon tetrachloride, including carcinogenicity.


Watts, J. L., E. Phillips, et al. (2003). "Deficiencies in C20 polyunsaturated fatty acids cause behavioral and developmental defects in Caenorhabditis elegans fat-3 mutants." Genetics 163(2): 581-9.

            Arachidonic acid and other long-chain polyunsaturated fatty acids (PUFAs) are important structural components of membranes and are implicated in diverse signaling pathways. The Delta6 desaturation of linoleic and linolenic acids is the rate-limiting step in the synthesis of these molecules. C. elegans fat-3 mutants lack Delta6 desaturase activity and fail to produce C20 PUFAs. We examined these mutants and found that development and behavior were affected as a consequence of C20 PUFA deficiency. While fat-3 mutants are viable, they grow slowly, display considerably less spontaneous movement, have an altered body shape, and produce fewer progeny than do wild type. In addition, the timing of an ultradian rhythm, the defecation cycle, is lengthened compared to wild type. Since all these defects can be ameliorated by supplementing the nematode diet with gamma-linolenic acid or C20 PUFAs of either the n6 or the n3 series, we can establish a causal link between fatty acid deficiency and phenotype. Similar epidermal tissue defects and slow growth are hallmarks of human fatty acid deficiency.


Wattanapenpaiboon, N. and M. W. Wahlqvist (2003). "Phytonutrient deficiency: the place of palm fruit." Asia Pac J Clin Nutr 12(3): 363-8.

            The oil palm (Elaeis guineensis) is native to many West African countries, where local populations have used its oil for culinary and other purposes. Large-scale plantations, established principally in tropical regions (Asia, Africa and Latin America), are mostly aimed at the production of oil, which is extracted from the fleshy mesocarp of the palm fruit, and endosperm or kernel oil. Palm oil is different from other plant and animal oils in that it contains 50% saturated fatty acids, 40% unsaturated fatty acids, and 10% polyunsaturated fatty acids. The fruit also contains components that can endow the oil with nutritional and health beneficial properties. These phytonutrients include carotenoids (alpha-,beta-,and gamma-carotenes), vitamin E (tocopherols and tocotrienols), sterols (sitosterol, stigmasterol and campesterol), phospholipids, glycolipids and squalene. In addition, it is recently reported that certain water-soluble powerful antioxidants, phenolic acids and flavonoids, can be recovered from palm oil mill effluent. Owing to its high content of phytonutrients with antioxidant properties, the possibility exists that palm fruit offers some health advantages by reducing lipid oxidation, oxidative stress and free radical damage. Accordingly, use of palm fruit or its phytonutrient-rich fractions, particularly water-soluble antioxidants, may confer some protection against a number of disorders or diseases including cardiovascular disease, cancers, cataracts and macular degeneration, cognitive impairment and Alzheimer's disease. However, whilst prevention of disease through use of these phytonutrients as in either food ingredients or nutraceuticals may be a worthwhile objective, dose response data are required to evaluate their pharmacologic and toxicologic effects. In addition, one area of concern about use of antioxidant phytonutrients is how much suppression of oxidation may be compatible with good health, as toxic free radicals are required for defence mechanisms. These food-health concepts would probably spur the large-scale oil palm (and monoculture) plantations, which are already seen to be a major cause of deforestation and replacement of diverse ecosystems in many countries. However, the environmental advantages of palm phytonutrients are that they are prepared from the readily available raw material from palm oil milling processes. Palm fruit, one of only a few fatty fruits, is likely to have an increasingly substantiated place in human health, not only through the provision of acceptable dietary fats, but also its characteristic protective phytonutrients.


Watkins, B. A., Y. Li, et al. (2003). "Modulatory effect of omega-3 polyunsaturated fatty acids on osteoblast function and bone metabolism." Prostaglandins Leukot Essent Fatty Acids 68(6): 387-98.

            Recent investigations indicate that the type and amount of polyunsaturated fatty acids (PUFA) influence bone formation in animal models and osteoblastic cell functions in culture. In growing rats, supplementing the diet with omega-3 PUFA results in greater bone formation rates and moderates ex vivo prostaglandin E(2) production in bone organ cultures. A protective effect of omega-3 PUFA on minimizing bone mineral loss in ovariectomized rats has also been reported. The actions of omega-3 fatty acids on bone formation appear to be linked to altering osteoblast functions. Herein we describe experiments with MC3T3-E1 osteoblast-like cells that support findings in vivo where omega-3 PUFA modulated COX-2 protein expression, reduced prostaglandin E(2) production, and increased alkaline phosphatase activity. Other studies indicate that the dietary source of PUFA may affect protein expression of Cbfa1 and nodule formation in fetal rat calvarial cells.


Watkins, B. A., S. Feng, et al. (2003). "Conjugated linoleic acids alter the fatty acid composition and physical properties of egg yolk and albumen." J Agric Food Chem 51(23): 6870-6.

            Effects of dietary conjugated linoleic acids (CLAs) and docosahexaenoic acid (DHA) on the fatty acid composition of different egg compartments after storage were studied. Four dietary treatments [supplemented with safflower oil (SAFF, control group), DHA, CLAs plus DHA (CAD), and CLAs alone] were administered to Single Comb White Leghorn (SCWL) laying hens. Eggs from the different treatment groups were collected and stored for 10 weeks at 4 degrees C before analysis. Fatty acids from the yolk (yolk granules and plasma), egg albumen, and vitelline membrane were analyzed by gas chromatography. The yolk of eggs from hens given CLAs had significantly higher amounts of saturated fatty acids, typically 16:0 and 18:0, but lower amounts of polyunsaturated fatty acids (PUFAs) compared to eggs from the control group (SAFF). CLA content was highest in the yolk and present in both neutral and polar lipids, with the greatest concentrations in neutral lipids. DHA was incorporated mainly into yolk polar lipids. Lipids in yolk plasma and granules contained similar amounts of CLAs. The fatty acid compositions of vitelline membrane and egg albumen mirrored that of the egg yolk. CLA supplementation resulted in hard and rubbery yolks when compared to hard-cooked eggs from the control group. This study showed that feeding CLAs to hens led to accumulation of the isomers in polar and neutral lipids of the egg yolk and that these isomers migrated into egg albumen. Because the sensory properties of hard-cooked eggs were negatively affected by the enrichment of a mixture of CLA isomers in this study, further research should be conducted to evaluate how the different isomers alter the properties of egg yolk and albumen so that the quality of designed eggs containing CLAs and DHA can be improved.


Wang, Y., Q. Liu, et al. (2003). "Docosahexaenoic acid inhibits cytokine-induced expression of P-selectin and neutrophil adhesion to endothelial cells." Eur J Pharmacol 459(2-3): 269-73.

            Dietary polyunsaturated fatty acids, such as docosahexaenoic acid, may inhibit pathological processes involving endothelial cell activation. Herein, it was found that treatment of endothelial cells with docosahexaenoic acid dose dependently reduced neutrophil adhesion provoked by tumor necrosis factor-alpha (TNF-alpha). In fact, pretreatment with 100 microM of docosahexaenoic acid for 24 h decreased TNF-alpha-induced neutrophil adhesion by 50%. Moreover, this pretreatment with docosahexaenoic acid (100 microM, 24 h) down-regulated TNF-alpha-induced endothelial cell surface expression of P-selection by 75%. Importantly, immunoneutralization of P-selectin reduced neutrophil adhesion to TNF-alpha-activated endothelial cells by more than 50%, indicating a significant role of P-selectin in this model. On the other hand, CXC chemokines, i.e. macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC), are also important regulators of neutrophil activation and adhesion. However, pretreatment with docosahexaenoic acid had no effect on TNF-alpha-provoked production of MIP-2 and KC in endothelial cells. Our study provide evidence that docosahexaenoic acid inhibits expression of P-selectin and subsequent adhesion of neutrophils to endothelial cells in response TNF-alpha, which may help explain the anti-inflammatory effects exerted by docosahexaenoic acid.


Wang, H., I. D. Kozekov, et al. (2003). "Site-specific synthesis and reactivity of oligonucleotides containing stereochemically defined 1,N2-deoxyguanosine adducts of the lipid peroxidation product trans-4-hydroxynonenal." J Am Chem Soc 125(19): 5687-700.

            trans-4-Hydroxynonenal (HNE) is a major peroxidation product of omega-6 polyunsaturated fatty acids. The reaction of HNE with DNA gives four diastereomeric 1,N(2)-gamma-hydroxypropano adducts of deoxyguanosine; background levels of these adducts have been detected in animal tissue. Stereospecific syntheses of these four adducts at the nucleoside level have been accomplished. In addition, a versatile strategy for their site-specific incorporation into oligonucleotides has been developed. These adducts are destabilizing as measured by melting temperature when compared to an unadducted strand. The thermal destablization of the adducted 12-mers ranged from 5 to 16 degrees C and is dependent on the absolute stereochemistry of the adduct. The HNE adducts were also examined for their ability to form interstrand DNA-DNA cross-links when incorporated into a CpG sequence. We find that only one of the HNE stereoisomers formed interstrand DNA-DNA cross-links.


Wang, L., T. Yan, et al. (2003). "[Research advance in effects of harmful algal bloom species on zooplankton]." Ying Yong Sheng Tai Xue Bao 14(7): 1191-6.

            The research on the effects of harmful algal bloom (HAB) algae on zooplankton has been drawn more and more attention. This paper summarized the adverse effects of HAB algae on zooplankton, which included reduced survival, inhibited growth, reduced fecundity of female, fertilization failure of eggs or hatching failure of zygote, inhibited embryo development, naupliar abnormal development or abnormality, inhibited grazing and changed behavior of zooplankton, etc. The main intoxication ways included decreased utilization of food, physiology impairment, damaged cell membrane, reduced gamete quality, and inhibited mitotic and embryo development by phycotoxins or exudations released by algae. Additionally, the lack of full nutrition, especially of polyunsaturated fatty acids in some algal species cells could also affect zooplankton growth and reproduction.


Wang, B., P. McVeagh, et al. (2003). "Brain ganglioside and glycoprotein sialic acid in breastfed compared with formula-fed infants." Am J Clin Nutr 78(5): 1024-9.

            BACKGROUND: The concentration of sialic acid in brain gangliosides and glycoproteins has been linked to learning ability in animal studies. Human milk is a rich source of sialic acid-containing oligosaccharides and is a potential source of exogenous sialic acid. OBJECTIVE: The aim of the study was to compare the sialic acid concentration in the brain frontal cortex of breastfed and formula-fed infants. DESIGN: Twenty-five samples of frontal cortex derived from infants who died of sudden infant death syndrome were analyzed. Twelve infants were breastfed, 10 infants were formula-fed, and 1 infant was mixed-fed; the feeding status of the remaining 2 infants was unknown. Ganglioside-bound and protein-bound sialic acid were determined by HPLC. Ganglioside ceramide fatty acids were also analyzed to determine the relation between sialic acid and long-chain polyunsaturated fatty acids. RESULTS: After adjustment for sex with age at death as a covariate, ganglioside-bound and protein-bound sialic acid concentrations were 32% and 22% higher, respectively, in the frontal cortex gray matter of breastfed infants than in that of formula-fed infants (P < 0.01). Protein-bound sialic acid increased with age in both groups (P = 0.02). In breastfed but not in formula-fed infants, ganglioside-bound sialic acid correlated significantly with ganglioside ceramide docosahexaenoic acid and total n-3 fatty acids. CONCLUSIONS: Higher brain ganglioside and glycoprotein sialic acid concentrations in infants fed human milk suggests increased synaptogenesis and differences in neurodevelopment.


Wang, L., A. R. Folsom, et al. (2003). "Plasma fatty acid composition and incidence of coronary heart disease in middle aged adults: the Atherosclerosis Risk in Communities (ARIC) Study." Nutr Metab Cardiovasc Dis 13(5): 256-66.

            BACKGROUND AND AIM: To prospectively investigate the relation of plasma cholesterol ester (CE) and phospholipid (PL) fatty acid (FA) composition with incidence of coronary heart disease (CHD). METHODS AND RESULTS: 3,591 white participants in the Minneapolis field center of the Atherosclerosis Risk in Communities Study, aged 45-64 years, were studied. Plasma FA composition of CEs and PLs was quantified using gas-liquid chromatography and expressed as percentage of total FAs. Incident CHD was identified during 10.7 years of follow-up. In both CE and PL fractions, the proportions of stearic (18:0) acid, dihomo-gamma-linolenic (20:3n6) acid and total saturated fatty acids (SFAs) were significantly higher while arachidonic (20:4n6) acid and total polyunsaturated fatty acids (PUFAs) were significantly lower among participants who developed incident CHD (n = 282). After adjusting for age, gender, smoking, alcohol drinking, sports activity, and non-FA dietary factors, the incidence of CHD was significantly and positively associated with the proportion of dihomo-gamma-linolenic acid but inversely associated with arachiadonic acid. The multiply-adjusted rate ratios (RRs) of CHD incidence for the highest versus the lowest quintile were 1.31 in CE and 1.44 in PL for dihomo-gamma-linolenic acid (p for trend: 0.05 and 0.017, respectively), 0.59 in CE and 0.65 in PL for arachidonic acid (p: 0.016 and 0.024, respectively). Also significantly and positively associated with incident CHD were PL stearic acid and CE linolenic (18:3n3) acid. Only a borderline significant positive association was observed for total SFAs in CE (multivariate RRs across quintiles: 1.00, 1.15, 1.40, 1.62, 1.32; p = 0.07). Total PUFAs or monounsaturated FA were not independently associated with CHD. CONCLUSIONS: Our study found a weak positive association of SFAs with incident CHD. Our findings also confirm that FA metabolism in the body, such as the activity of delta-5 desaturase, which converts dihomo-gamma-linolenic acid to arachidonic acid, may affect the development of CHD.


Wallace, F. A., E. A. Miles, et al. (2003). "Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects." Br J Nutr 89(5): 679-89.

            Studies on animal and human subjects have shown that greatly increasing the amount of linseed (also known as flaxseed) oil (rich in the n-3 polyunsaturated fatty acid (PUFA) alpha-linolenic acid (ALNA)) or fish oil (FO; rich in the long-chain n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) in the diet can decrease a number of markers of immune function. The immunological effects of more modest doses of n-3 PUFA in human subjects are unclear, dose-response relationships between n-3 PUFA supply and immune function have not been established and whether ALNA has the same effects as its long-chain derivatives is not known. Therefore, the objective of the present study was to determine the effect of enriching the diet with different doses of FO or with a modest dose of ALNA on a range of functional responses of human monocytes and lymphocytes. In a randomised, placebo-controlled, double-blind, parallel study, forty healthy males aged 18-39 years were randomised to receive placebo or 3.5 g ALNA/d or 0.44, 0.94 or 1.9 g (EPA+DHA)/d in capsules for 12 weeks. The EPA:DHA ratio in the FO used was 1.0:2.5. ALNA supplementation increased the proportion of EPA but not DHA in plasma phospholipids. FO supplementation decreased the proportions of linoleic acid and arachidonic acid and increased the proportions of EPA and DHA in plasma phospholipids. The interventions did not alter circulating mononuclear cell subsets or the production of tumour necrosis factor-alpha, interleukin (IL) 1beta, IL-2, IL-4, IL-10 or interferon-gamma by stimulated mononuclear cells. There was little effect of the interventions on lymphocyte proliferation. The two higher doses of FO resulted in a significant decrease in IL-6 production by stimulated mononuclear cells. It is concluded that, with the exception of IL-6 production, a modest increase in intake of either ALNA or EPA+DHA does not influence the functional activity of mononuclear cells. The threshold of EPA+DHA intake that results in decreased IL-6 production is between 0.44 and 0.94 g/d.


Walkowiak, J. and J. Przyslawski (2003). "Five-year prospective analysis of dietary intake and clinical status in malnourished cystic fibrosis patients." J Hum Nutr Diet 16(4): 225-31.

            BACKGROUND: Poor growth and malnutrition still pose a problem in cystic fibrosis (CF). The aim of the present study was to assess nutrition, as well as clinical status, of malnourished CF patients during a nutritional care programme. MATERIAL AND METHODS: The study comprised 38 CF patients, aged 1-18 years old. The prospective annual assessment of dietary intake and clinical status was carried out during 1994-98. RESULTS: The energy intake increased, in comparison with recommended daily allowances, from 83.6 +/- 4.8% in 1994 to 107.9 +/- 4.9% in 1998. A similar tendency was observed for the percentage of energy derived from fat (30.3 +/- 0.8% versus 35.1 +/- 0.8%) and protein (11.4 +/- 0.4% versus 13.8 +/- 0.4%). In subsequent years of the study, an improvement in the fat profile of the diet (with a higher consumption of polyunsaturated fatty acids) was observed. The observed increase of vitamin A and E consumption was related chiefly to changes in the doses of supplementation. During these 5 years, an improvement in nutritional status (Z-score: height -1.34 +/- 0.13 versus -1.08 +/- 0.14 and weight -1.40 +/- 0.09 versus -1.12 +/- 0.08) and lung function (forced expiratory volume in 1 s: 75.5 +/- 2.0% versus 77.8 +/- 2.2%) was observed. CONCLUSION: The nutritional care programme resulted in stable quantitative and qualitative changes in dietary intake. Although the diet does not reach the recommended level of high-energy intake, the positive impact of increasing nutrient intake on the nutritional and clinical status of malnourished CF patients was documented.


Walkowiak, J., M. Wilczynski, et al. (2003). "The predominance of omega-6 polyunsaturated fatty acids in cystic fibrosis despite low arachidonic acid levels." Acta Paediatr 92(11): 1354-5.


Wahle, K. W., D. Rotondo, et al. (2003). "Polyunsaturated fatty acids and gene expression in mammalian systems." Proc Nutr Soc 62(2): 349-60.

            Over the last 30 years it has become apparent that specific dietary fatty acids are capable of regulating, either directly or indirectly through various signal pathways, the expression of numerous genes, either positively or negatively. Such nutrient-gene interactions have important effects on cell metabolism, differentiation and growth, and ultimately on disease processes. The present review describes some of the more important fatty acid-gene interactions in relation to health and disease in mammalian species, and focuses on the underlying cell signal mechanisms, including various transcription factors, affected by fatty acids and some of their oxygenated derivatives, e.g. the eicosanoids. The review also attempts to clarify some of the complexities of the effects of fatty acids by suggesting a possible overriding regulation by the redox status of the cell. The latter will at least stimulate controversy in this exciting area of lipid research.


Wacker, A. and E. Von Elert (2003). "Food quality controls reproduction of the zebra mussel (Dreissena polymorpha)." Oecologia 135(3): 332-8.

            Species such as Dreissena polymorpha sometimes contribute substantially in the transfer of primary to secondary production. During the ontogenetic cycle, the reproductive investment of adult mussels is one of the main parameters that affect recruitment success. We studied how food quality and temperature affect the reproductive investment in term of egg mass of D. polymorpha in a lake by sampling mussels monthly from 4 m and 15 m depths. Temperature affected reproduction directly and also indirectly through the food. To assess whether temperature and/or food conditions led to the differences observed in mussels sampled from the two depths, mussels were reared in the laboratory under two different temperature regimes for 3 months, simulating the temperature of the lake at 4 m and 15 m depth. Possible effects of food quality were tested at each temperature using four diets differing in fatty acid composition. Temperature played an important role as a trigger for spawning, and the type of diet clearly affected the reproductive investment. When the heterokont chromophyte alga Nannochloropsis limnetica, which is rich in polyunsaturated fatty acids (PUFAs) and long-chained PUFAs (>C18), was fed to mussels, an increased egg mass was obtained. This result was in contrast to that found when the green alga Scenedesmus obliquus and the cyanobacterium Aphanothece sp., both of which are deficient in long-chained PUFAs, were offered as food to the mussels. Such a PUFA-dependent food quality may affect reproduction in lakes. Food quality effects vary seasonally in a lake and may be most important in summer, when low-food-quality green algae and cyanobacteria are abundant. The low biochemical quality of these blooms may affect at least the later period of gametogenesis of D. polymorpha, which reproduces from June to August.


Vuong, L. T. and J. C. King (2003). "A method of preserving and testing the acceptability of gac fruit oil, a good source of beta-carotene and essential fatty acids." Food Nutr Bull 24(2): 224-30.

            Gac fruit (Momordica cochinchinensis Spreng) is indigenous to Vietnam and other countries in Southeast Asia. Its seed pulp contains high concentrations of carotenoids, especially the provitamin A, beta-carotene. In northern Vietnam, gac fruits are seasonal and are mainly used in making a rice dish called xoi gac. The purpose of this study was to develop a method to collect and preserve gac fruit oil, to evaluate the nutritional composition of the oil, and to assess the acceptability of the gac oil by typical Vietnamese homemakers. One hundred women participated in training to learn how to prepare the fruits and operate the oil press. The women also participated in a survey of gac fruit use and their habitual use of animal fat and vegetable oil. Among all the participants in the training and surveys, 35 women actually produced oil from gac fruits grown in the village, using manual oil presses and locally available materials. The total carotene concentration in gac fruit oil was 5,700 micrograms/ml. The concentration of beta-carotene was 2,710 micrograms/ml. Sixty-nine percent of total fat was unsaturated, and 35% of that was polyunsaturated. The average daily consumption of gac fruit oil was estimated at 2 ml per person. The daily beta-carotene intake (from gac fruit oil) averaged approximately 5 mg per person. It was found that gac oil can be produced locally by village women using manual presses and locally available materials. The oil is a rich source of beta-carotene, vitamin E, and essential fatty acids. Although the beta-carotene concentration declines with time without a preservative or proper storage, it was still high after three months. The oil was readily accepted by the women and their children, and consumption of the oil increased the intake of beta-carotene and reduced the intake of lard.


von Schacky, C. (2003). "The role of omega-3 fatty acids in cardiovascular disease." Curr Atheroscler Rep 5(2): 139-45.

            Plant-derived alpha-linolenic acid has been studied in a limited number of investigations. So far, some epidemiologic and a few mechanistic studies suggest a potential of protection from cardiovascular disease, but this potential remains to be proven in intervention studies. In contrast, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are prevalent in fish and fish oils, have been studied in thousands of investigations. A consistent body of evidence has been elaborated in various types of investigations, ultimately demonstrating reduction in total mortality, cardiovascular mortality, and morbidity by ingestion of roughly 1 g/d of EPA plus DHA. Current guidelines, however, do not discern between the omega-3 fatty acids mentioned; in fact, most even do not differentiate polyunsaturated fatty acids at all. Unfortunately, this complicates efficient implementation of an effective means of prophylaxis of atherosclerosis.


von Elert, E., D. Martin-Creuzburg, et al. (2003). "Absence of sterols constrains carbon transfer between cyanobacteria and a freshwater herbivore (Daphnia galeata)." Proc R Soc Lond B Biol Sci 270(1520): 1209-14.

            A key process in freshwater plankton food webs is the regulation of the efficiency of energy and material transfer. Cyanobacterial carbon (C) in particular is transferred very inefficiently to herbivorous zooplankton, which leads to a decoupling of primary and secondary production and the accumulation of cyanobacterial biomass, which is associated with reduced recreational quality of water bodies and hazards to human health. A recent correlative field study suggested that the low transfer efficiency of cyanobacterial C is the result of the absence of long-chain polyunsaturated fatty acids (PUFA) in the diet of the zooplankton. By supplementation of single-lipid compounds in controlled growth experiments, we show here that the low C transfer efficiency of coccal and filamentous cyanobacteria to the keystone herbivore Daphnia is caused by the low sterol content in cyanobacteria, which constrains cholesterol synthesis and thereby growth and reproduction of the herbivore. Estimations of sterol requirement in Daphnia suggest that, when cyanobacteria comprise more than 80% of the grazed phytoplankton, growth of the herbivore may be limited by sterols and Daphnia may subsequently fail to control phytoplankton biomass. Dietary sterols therefore may play a key role in freshwater food webs and in the control of water quality in lakes dominated by cyanobacteria.


Viswanathan, S., B. D. Hammock, et al. (2003). "Involvement of CYP 2C9 in mediating the proinflammatory effects of linoleic acid in vascular endothelial cells." J Am Coll Nutr 22(6): 502-10.

            OBJECTIVE: Polyunsaturated fatty acids such as linoleic acid are well known dietary lipids that may be atherogenic by activating vascular endothelial cells. In the liver, fatty acids can be metabolized by cytochrome P450 (CYP) enzymes, but little is known about the role of these enzymes in the vascular endothelium. CYP 2C9 is involved in linoleic acid epoxygenation, and the major product of this reaction is leukotoxin (LTX). We investigated the role of CYP-mediated mechanisms of linoleic acid metabolism in endothelial cell activation by examining the effects of linoleic acid or its oxidized metabolites such as LTX and leukotoxin diol (LTD). METHODS: The effect of linoleic acid on CYP 2C9 gene expression was studied by RT-PCR. Oxidative stress was monitored by measuring DCF fluorescence and intracellular glutathione levels, and electrophoretic mobility shift assay was carried out to study the activation of oxidative stress sensitive transcription factors. Analysis of oxidized lipids was carried out by liquid chromatography/mass spectrometry. RESULTS: Linoleic acid treatment for six hours increased the expression of CYP 2C9 in endothelial cells. Linoleic acid-mediated increase in oxidative stress and activation of AP-1 were blocked by sulfaphenazole, a specific inhibitor of CYP 2C9. The linoleic acid metabolites LTX and LTD increased oxidative stress and activation of transcription factors only at high concentrations. CONCLUSION: Our data show that CYP 2C9 plays a key role in linoleic acid-induced oxidative stress and subsequent proinflammatory events in vascular endothelial cells by possibly causing superoxide generation through uncoupling processes.


Vigouroux, S., L. Farout, et al. (2003). "Increased muscle proteasome activities in rats fed a polyunsaturated fatty acid supplemented diet." Int J Biochem Cell Biol 35(5): 749-55.

            Changes in the proteasome system, a dominant actor in protein degradation in eukaryotic cells, have been documented in a large number of physiological and pathological conditions. We investigated the influence of monounsaturated or polyunsaturated fatty acids (PUFAs) supplemented diets on the proteasome system, in rat skeletal muscles. Thirty rats were randomly assigned to three groups. The control group received only a standard diet. The monounsaturated fatty acid (MUFA) enriched diet group was fed with 3% sunflower oil in addition to standard food, and the polyunsaturated fatty acid supplemented diet group received 9% Maxepa) in addition to the standard diet. We analyzed muscle proteasome activities and content. Monounsaturated or PUFAs supplemented diets given for 8 weeks induced a significant increase in proteasome activities. With the polyunsaturated fatty acid enriched diet, the chymotrypsin-like and peptidylglutamylpeptide hydrolase activities increased by 45% in soleus and extensor digitorum longus (EDL), and by 90% in the gastrocnemius medialis (GM) muscle. Trypsin-like activity of the proteasome increased by 250% in soleus, EDL and GM. This increase in proteasome activities was associated with a concomitant enhancement in the muscle content of proteasome. Proteasome activities and level were less stimulated with a monounsaturated fatty acid supplemented diet. This study provides evidence that a monounsaturated or polyunsaturated fatty acid supplemented diet may regulate muscle proteasomes. Unsaturated fatty acids are particularly prone to free radical attack. Thus, we suggest that alterations in muscle proteasome may result from monounsaturated and polyunsaturated fatty acid-induced peroxidation, in order to eliminate damaged proteins.


Vericel, E., A. Polette, et al. (2003). "Pro- and antioxidant activities of docosahexaenoic acid on human blood platelets." J Thromb Haemost 1(3): 566-72.

            n - 3 polyunsaturated fatty acids may protect against vascular diseases, however, their high accumulation in membranes may increase lipid peroxidation and subsequently induce deleterious effects in patients suffering from oxidative stress. This led us to investigate in vitro the dose-dependent effect of docosahexaenoic acid (DHA) on the redox status of human platelets. We have compared the effect of different DHA concentrations (0.5, 5 and 50 micro mol L(-1)) corresponding to DHA/albumin ratios of 0.01, 0.1 and 1. At the highest concentration, DHA elicited a marked oxidative stress, as evidenced by high malondialdehyde and low vitamin E levels whereas the lowest DHA concentration significantly decreased the malondialdehyde formation, with no change in vitamin E. The proportion of DHA was only increased in plasmalogen phosphatidylethanolamine at low concentration to rise in all phosphatidyl-choline and -ethanolamine subclasses at high concentration. Thus, the results show a biphasic effect of DHA with antioxidant and prooxidant effects at low and high concentrations, respectively, with a possible relationship with the phospholipid subclass in which it accumulates.


Veen, M. and C. Lang (2003). "Production of lipid compounds in the yeast Saccharomyces cerevisiae." Appl Microbiol Biotechnol.

            This review describes progress using the yeast Saccharomyces cerevisiae as a model organism for the fast and efficient analysis of genes and enzyme activities involved in the lipid biosynthetic pathways of several donor organisms. Furthermore, we assess the impact of baker's yeast on the production of novel, high-value lipid compounds. Yeast can be genetically modified to produce selected substances in relatively high amounts. A major advantage in choosing yeast as an object for metabolic engineering is the fact that the lipid pathways in this organism have been described in detail and are well characterized. We focus on the de novo production of three major families of lipid products. These are: (1) sterols, providing some previously known and some novel applications as examples of the lipid pathway enhancement that occurs naturally in yeast, (2) the reconstitution of the biosynthetic pathway of steroid hormones and (3) the biosynthesis of polyunsaturated fatty acids, leading to the biosynthesis of different omega-3 and omega-6 fatty acids which do not occur naturally in yeast. We utilize the current knowledge and point out perspectives and problems for future biotechnological applications in the field of lipid compounds.


Vecera, R., N. Skottova, et al. (2003). "Antioxidant status, lipoprotein profile and liver lipids in rats fed on high-cholesterol diet containing currant oil rich in n-3 and n-6 polyunsaturated fatty acids." Physiol Res 52(2): 177-87.

            Plant-based n-3 polyunsaturated fatty acids (PUFA) possess a prospective antiatherogenic potential. Currant oil from Ribes nigrum L. is one of the few plant oils containing PUFAn-3 (15.3 mol%) in addition to PUFAn-6 (60.5 mol%). This study was aimed at comparing the effects of currant oil with those of lard fat, rich in saturated (43.8 mol%) and monounsaturated (47.0 mol%) fatty acids, on antioxidant parameters, the lipoprotein profile and liver lipids in rats fed on 1 % (w/w) cholesterol diets containing either 10 % of currant oil (COD) or lard fat (LFD). After 3 weeks of feeding, the COD induced a significant decrease in blood glutathione (GSH) and an increase in Cu(2+) induced oxidizability of serum lipids, but did not affect liver GSH and t-butyl hydroperoxide-induced lipoperoxidation of liver microsomes. Although the COD did not cause accumulation of liver triacylglycerols as LFD, the lipoprotein profile (VLDL, LDL, HDL) was not significantly improved after COD. The consumption of PUFAn-3 was reflected in LDL as an increase in eicosapentaenoic and docosahexaenoic acid. These results suggest that currant oil affects positively the lipid metabolism in the liver, above all it does not cause the development of a fatty liver. However, adverse effects of currant oil on the antioxidant status in the blood still remain of concern.


Vanschoonbeek, K., M. P. de Maat, et al. (2003). "Fish oil consumption and reduction of arterial disease." J Nutr 133(3): 657-60.

            Fish oil consumption may help to normalize the prethrombotic state and reduce arterial disease. This antithrombotic potential of fish oil, rich in (n-3) polyunsaturated fatty acids (PUFA), has been attributed to a reduction in platelet activation, a lowering of plasma triglycerides and (vitamin K-dependent) coagulation factors and/or a decrease in vascular tone. Most intervention studies have shown only moderate effects of (n-3) PUFA on these hemostatic variables. On the other hand, the usually small prolongation in bleeding time with fish oil does not appear to lead to bruising or hemorrhage, at least in healthy subjects. This contrasts with the increased bleeding risk accompanying the more prominent antihemostatic effects of antiplatelet and anticoagulant drugs. Here we propose that the beneficial effect of (n-3) PUFA diet is related to down-regulation of the mutually positive interactions of platelet activation and coagulation. In addition, we consider the possibility that the dietary effect on hemostatic and lipid factors involves transcription regulation of multiple genes, perhaps in a subject-dependent manner.


VanderJagt, D. J., M. R. Trujillo, et al. (2003). "Phase angle correlates with n-3 fatty acids and cholesterol in red cells of Nigerian children with sickle cell disease." Lipids Health Dis 2(1): 2.

            OBJECTIVE: To determine the cholesterol content and fatty acid composition of red cell membrane phospholipids (PL) of children with sickle cell disease (SCD) and to correlate these levels with whole body phase angle that is related to the integrity and function of cell membranes. STUDY DESIGN: Blood samples were obtained from 69 children with SCD and 72 healthy age- and gender-matched controls in Nigeria for the determination of the cholesterol content and proportions of fatty acids in red cell PL. Bioelectrical impedance analysis was used to obtain resistance (R) and reactance (Xc) from which phase angle was calculated as arctan Xc/R. Cholesterol (normalized to lipid phosphorus) and the proportions of individual fatty acids were correlated with phase angle. RESULTS: The proportions of palmitic (p < 0.001), stearic acid (p = 0.003) and cholesterol (p < 0.001) were significantly higher in the red cells of children with SCD, whereas the proportions of arachidonic acid and docosahexaenoic acid were reduced (p = 0.03 and < 0.001, respectively) compared to controls. The phase angle was inversely correlated with the proportions of palmitic acid (p = 0.03) and oleic acid (p < 0.001) and cholesterol (p = 0.003). Three n-3 polyunsaturated fatty acids-eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid- were positively correlated with phase angle (p < 0.001). CONCLUSIONS: The fatty acid composition and cholesterol content of tissue membranes in SCD correlate with the phase shift measured by bioelectrical impedance analysis. Phase angle measurements may provide a non-invasive method for monitoring interventions aimed at altering the lipid composition of membranes.


van Haaften, R. I., G. R. Haenen, et al. (2003). "Effect of vitamin E on glutathione-dependent enzymes." Drug Metab Rev 35(2-3): 215-53.

            Reactive oxygen species and various electrophiles are involved in the etiology of diseases varying from cancer to cardiovascular and pulmonary disorders. The human body is protected against damaging effects of these compounds by a wide variety of systems. An important line of defense is formed by antioxidants. Vitamin E (consisting of various forms of tocopherols and tocotrienols) is an important fat-soluble, chain-breaking antioxidant. Besides working as an antioxidant, this compound possesses other functions with possible physiological relevance. The glutathione-dependent enzymes form another line of defense. Two important enzymes in this class are the free radical reductase and glutathione S-transferases (GSTs). The GSTs are a family of phase II detoxification enzymes. They can catalyze glutathione conjugation with various electrophiles. In most cases the electrophiles are detoxified by this conjugation, but in some cases the electrophiles are activated. Antioxidants do not act in isolation but form an intricate network. It is, for instance, known that vitamin E, together with glutathione (GSH) and a membrane-bound heat labile GSH-dependent factor, presumably an enzyme, can prevent damaging effects of reactive oxygen species on polyunsaturated fatty acids in biomembranes (lipid peroxidation). This manuscript reviews the interaction between the two defense systems, vitamin E and glutathione-dependent enzymes. On the simplest level, antioxidants such as vitamin E have protective effects on glutathione-dependent enzymes; however, we will see that reality is somewhat more complicated.


Valencak, T. G., W. Arnold, et al. (2003). "High content of polyunsaturated fatty acids in muscle phospholipids of a fast runner, the European brown hare (Lepus europaeus)." J Comp Physiol [B] 173(8): 695-702.

            To investigate both seasonal changes and possible intracorporal gradients of phospholipid fatty acid composition, skeletal muscles ( n=124), hearts ( n=27), and livers ( n=34) from free-living brown hares (Lepus europaeus) were analyzed. Phospholipids from both skeletal muscles and heart had a high degree of unsaturation with 66.8+/-0.63% and 65.7+/-0.5% polyunsaturated fatty acids, respectively. This is the highest proportion of polyunsaturated fatty acids reported in any mammalian tissue. Polyunsaturated fatty acid content in skeletal muscles was 2.3% greater in winter compared to summer (F(1,106)=17.7; P=0.0001), which may reflect thermoregulatory adjustments. Arachidonate (C20:4n-6) showed the greatest seasonal increase (+2.5%; F=7.95; P=0.0057). However, there were no pronounced differences in polyunsaturated fatty acid content between skeletal muscles from different locations in the body (m. iliopsoas, m. longissimus dorsi and m. vastus). Total muscle phospholipid polyunsaturated fatty acid content was correlated with polyunsaturated fatty acid content in triacyglycerols from perirenal white adipose tissue depots ( r(2)=0.61; P=0.004). Polyunsaturated fatty acids were enriched in muscle phospholipids (56.8-73.6%), compared to white adipose tissue lipids (20.9-61.2%), and liver phospholipids (25.1-54.2%). We suggest that the high degree of muscle membrane unsaturation is related to hare-specific traits, such as a high maximum running speed.


Utsunomiya, T., M. Shimada, et al. (2003). "Antioxidant and anti-inflammatory effects of a diet supplemented with sesamin on hepatic ischemia-reperfusion injury in rats." Hepatogastroenterology 50(53): 1609-13.

            BACKGROUND/AIMS: The antioxidant and anti-inflammatory properties of sesamin (a non-fat constituent of sesame oil) have been attributed to an increased accumulation of dihomo-y-linolenic acid, a precursor of 1-series prostaglandins, and the decreasing production of proinflammatory 2-series prostaglandins and 4-series leukotrienes by inhibiting the delta-5 desaturase activity. We investigated the effects of a diet containing sesamin on hepatic ischemia-reperfusion injury in rats. METHODOLOGY: After feeding rats either a basal diet (control group) or a diet supplemented with sesamin (sesamin group) for 14 days, the rats underwent 60 minutes of partial hepatic ischemia and 3 hours of reperfusion. The phospholipid fatty acid composition of both liver and lung tissue specimens were then analyzed. The plasma levels of leukotriene B4 and PCOOH (phosphatidylcholine hydroperoxide) were also determined. RESULTS: The consumption of the dietary sesamin resulted in a significant increase in the dihomo-y-linolenic acid content in the tissue phospholipids of the liver and lung specimens. The amounts of polyunsaturated fatty acids in the lungs subjected to the ischemia-reperfusion injury were well preserved in the animals from the sesamin group. Despite a lack of differences in the levels of arachidonic acid, the plasma levels of leukotriene B4 in the rats fed dietary sesamin (88 +/- 15 pg) tended to be lower (P = 0.07) than those fed the control diet (110 +/- 20 pg). Furthermore, the plasma concentrations of PCOOH in the sesamin group (130 +/- 62 pmol) were also significantly lower (P < 0.05) than those in the control group (223 +/- 33 pmol). CONCLUSIONS: These findings indicate that a diet containing sesamin may thus reduce hepatic ischemia-reperfusion injury by inducing both antioxidant and anti-inflammatory activities.


Usami, M., T. Komurasaki, et al. (2003). "Effect of gamma-linolenic acid or docosahexaenoic acid on tight junction permeability in intestinal monolayer cells and their mechanism by protein kinase C activation and/or eicosanoid formation." Nutrition 19(2): 150-6.

            OBJECTIVE: Polyunsaturated fatty acids have been characterized as immunonutrients, but the effect of gamma-linolenic acid (GLA) or docosahexaenoic acid (DHA) on intestinal permeability has rarely been reported. METHODS: Confluent Caco-2 cells on porous filter were used to measure tight junction function by fluorescein sulfonic acid permeability and transepithelial electrical resistance. Treatments with 0, 10, 50, and 100 microM of GLA or DHA during 24 h were compared. Then the effects of butylated hydroxytoluene (antioxidant), 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (protein kinase C antagonist), and inhibitors of enzymatic degradation to the eicosanoids, indomethacin (cyclooxygenase inhibitor) and 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-p-benzoquinone (lipoxygenase inhibitor), on GLA or DHA were examined. RESULTS: GLA and DHA enhanced fluorescein sulfonic acid permeability to 8.7- and 1.4-fold, respectively, and lowered transepithelial electrical resistance to 0.52- and 0.73-fold, respectively, versus the control in a concentration-dependent manner without cell injury (P < 0.001 to 0.05). Indomethacin and 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-p-benzoquinone enhanced the changes mediated by GLA but did not alter the DHA effect. Butylated hydroxytoluene was ineffective. 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine facilitated the changes mediated by GLA, DHA, and eicosapentaenoic acid. The results indicated that the mechanism to change tight junction permeability via protein kinase C regulation is common but that via eicosanoid formation differs among GLA, DHA, and eicosapentaenoic acid. CONCLUSIONS: GLA and DHA affect tight junction permeability in intestinal monolayer cells specifically and in a concentration-dependent manner.


Uauy, R., D. R. Hoffman, et al. (2003). "Term infant studies of DHA and ARA supplementation on neurodevelopment: results of randomized controlled trials." J Pediatr 143(4 Suppl): S17-25.

            Healthy term infants who are not breast-fed may need long-chain polyunsaturated fatty acids (LCPUFA) in their feeding, based on the changes in plasma and tissue fatty composition. However, consistent functional effects across different studies conducted over the past two decades has been more difficult to document. The interpretation of these data has scientific and public interest with the introduction of LCPUFA supplemented formula. There are 14 controlled trials in term infants that have included formula feeding with or without LCPUFA and functional assessment of visual and other measures of neural development; in addition, 7 have evaluated specific measures related to cognitive development. We chose to examine the effect of DHA dose provided daily on the development of visual acuity to explain the differences in visual acuity responses across randomized studies. A "meta-regression" was performed with the use of a DHA effective dose as the independent variable and visual acuity at 4 months as the dependent variable. Since the two main dietary determinants of DHA status are the LNA provided and the preformed DHA consumed, we defined DHA equivalent dose across studies by assuming a 1%, 5%, and 10% conversion of LNA to DHA. Results indicate a strong and significant effect of DHA equivalent dose on magnitude of the visual acuity response at all conversions tested; greatest significance was found when using a 10% bioequivalency (r(2)=0.68, and P=.001). We conclude that there is a significant relation between the total DHA equivalents provided and effectiveness as defined by visual acuity measurements at 4 months of age.


Tuyet Mai, T., N. Kim Hung, et al. (2003). "Macronutrient intake and nutritional status of primary school-aged girls in rural and urban areas of South Vietnam." J Nutr Sci Vitaminol (Tokyo) 49(1): 13-20.

            The dietary habits and nutritional status of Vietnamese primary school girls were investigated using a cross-sectional survey. We interviewed 348 girls aged 7 to 9 yr old, randomly selected from three rural (n=193) and two urban (n=155) primary schools. The nutritional status of the children was evaluated by anthropometric and biochemical data. Dietary data were calculated based on the results of a 24-h recall interview carried out for three consecutive days. The dietary macronutrient pattern of the rural group showed a deficiency of energy, fat, animal protein, and fiber content. On the other hand, high animal protein ratio, deficiency of fiber consumption, low polyunsaturated fatty acid, and high saturated fatty acid proportions were typically found in the urban group. A high number of rural children skipped lunches, resulting in low energy consumption: however, frequently skipped breakfast in the urban group did not influence total energy consumption because of extra meals taken. The mean height of rural children was 5.8 cm less than that of their urban counterparts. In addition, 11.4% of wasted rural children needed emergency intervention with energy supplementation. Moreover, a high proportion of children with a high atherogenic index (AI) (41.5%) and low HDL cholesterol (40.9%) were found in the rural group. In contrast, a tendency toward obesity, high cholesterol, LDL cholesterol, and high AI was observed in a proportion of the urban children (5.2%, 15.5%, 12.3%, and 29.0%, respectively).


Tully, A. M., H. M. Roche, et al. (2003). "Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case-control study." Br J Nutr 89(4): 483-9.

            Low n-3 polyunsaturated fatty acid (PUFA) status may be associated with neuro-degenerative disorders, in particular Alzheimer's disease, which has been associated with poor dietary fish or n-3 PUFA intake, and low docosahexaenoic acid (DHA) status. The present case-control study used an established biomarker of n-3 PUFA intake (serum cholesteryl ester-fatty acid composition) to determine n-3 PUFA status in patients with Alzheimer's disease, who were free-living in the community. All cases fulfilled the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease. Detailed neuropsychological testing and neuroimaging established the diagnosis in all cases. The subjects (119 females and twenty-nine males) aged 76.5 (SD 6.6) years had a clinical dementia rating (CDR) of 1 (SD 0.62) and a mini mental state examination (MMSE) score of 19.5 (SD 4.8). The control subjects (thirty-six females and nine males) aged 70 (SD 6.0) years were not cognitively impaired (defined as MMSE score <24): they had a mean MMSE score of 28.9 (SD 1.1). Serum cholesteryl ester-eicosapentaenoic acid and DHA levels were significantly lower (P<0.05 and P<0.001 respectively) in all MMSE score quartiles of patients with Alzheimer's disease compared with control values. Serum cholesteryl ester-DHA levels were progressively reduced with severity of clinical dementia. DHA levels did not differ in patients with Alzheimer's disease across age quartiles: all were consistently lower than in control subjects. Step-wise multiple regression analysis showed that cholesteryl ester-DHA and total saturated fatty acid levels were the important determinants of MMSE score and CDR. It remains to be determined whether low DHA status in Alzheimer's disease is a casual factor in the pathogenesis and progression of Alzheimer's disease.


Tsuji, M., S. I. Murota, et al. (2003). "Docosapentaenoic acid (22:5, n-3) suppressed tube-forming activity in endothelial cells induced by vascular endothelial growth factor." Prostaglandins Leukot Essent Fatty Acids 68(5): 337-42.

            It is generally accepted that n-3 polyunsaturated fatty acids have beneficial effects on vascular homeostasis. Among the several functions of endothelial cells, angiogenesis contributes to tumor growth, inflammation, and microangiopathy. We have already demonstrated that eicosapentaenoic acid (EPA, 20:5, n-3) suppressed angiogenesis. In this paper, we examined the effect of docosapentaenoic acid (DPA, 22:5, n-3), an elongated metabolite of EPA, on tube-forming activity in bovine aortic endothelial cells (BAE cells) incubated between type I collagen gels. The pretreatment of BAE cells with DPA suppressed tube-forming activity induced by vascular endothelial growth factor (VEGF). The effect of DPA was stronger than those of EPA and docosahexaenoic acid (22:6, n-3). The migrating activity of endothelial cells stimulated with VEGF was also suppressed by DPA pretreatment. The treatment of BAE cells with DPA caused the suppression of VEGF receptor-2 (VEGFR-2, the kinase insert domain-containing receptor, KDR) expression in both plastic dish and collagen gel cultures. These data indicate that DPA has a potent inhibitory effect on angiogenesis through the suppression of VEGFR-2 expression.


Tsuji, K., Y. Kawai, et al. (2003). "Formation of N-(hexanoyl)ethanolamine, a novel phosphatidylethanolamine adduct, during the oxidation of erythrocyte membrane and low-density lipoprotein." Biochem Biophys Res Commun 306(3): 706-11.

            The primary amino groups of biomolecules such as aminophospholipids, as well as proteins, are the potential targets of covalent modifications by lipid peroxidation products; however, little attention has been paid to the modification of aminophospholipids such as phosphatidylethanolamine (PE). The purpose of this study was to characterize the formation of a novel modified phospholipid, N-(hexanoyl)phosphatidylethanolamine (HEPE), in the reaction of PE with lipid hydroperoxides using mass spectrometric analyses. Upon reaction of egg PE with 13-hydroperoxyoctadecadienoic acid or other oxidized polyunsaturated fatty acids followed by phospholipase D-mediated hydrolysis, the formation of N-(hexanoyl)ethanolamine (HEEA), a head group of HEPE, was confirmed by isotope dilution liquid chromatography/tandem mass spectrometry. Moreover, increasing HEEA was detected in the hydrolysates of oxidized erythrocyte ghosts and low-density lipoprotein with their increasing lipid peroxidation levels. Collectively, these results suggest that the N-hexanoylated product of phospholipid, HEPE, can be generated during lipid peroxidation and may serve as one mechanism for the covalent modification of aminophospholipids in vivo.


Trushina, E. N., O. K. Mustafina, et al. (2003). "[The mechanism of action of polyunsaturated fatty acids on the immune system]." Vopr Pitan 72(3): 35-40.

            This article presents the literature materials about polyunsaturated fatty acids as nutritional immunomodulators.


Trushina, E. N., O. K. Mustafina, et al. (2003). "[The influence of the dietary polyunsaturated fatty acids on the phagocyte's functional activity in rats]." Vopr Pitan 72(4): 9-11.

            The influence of dietary polyunsaturated fatty acids on the superoxid anion production by peritoneal macrophages and phagocytosis by blood neutrophiles in male Wistar rats weighting 127.0 +/- 3.2 r was investigated after 3 months feeding. Rats fed isocaloric purified diets contained 24% fat representing combinations of lard, sunflower oil and fish oil (eiconol) providing the ratios of w6/w3 fatty acids equal 49.0; 6.1; 1.1. The increasing of superoxide formed by peritoneal macrophages and phagocytic activity of neutrophiles in the group received diet with the minimal ratios of w6/w3 fatty acids compared to that in rats fed diet with ratio 49.0 was noted. The increased activity of mononuclear-phagocytic system was confirmed by morphological investigation of peripheral lymphoid organs.


Triantafillou, D., V. Zografos, et al. (2003). "Fatty acid content of margarines in the Greek market (including trans-fatty acids): a contribution to improving consumers' information." Int J Food Sci Nutr 54(2): 135-41.

            The fatty acid composition, including trans-fatty acids, of 15 margarine samples from the Greek market was determined by gas-liquid chromatography. Saturated, cis-monounsaturated and polyunsaturated fatty acids have been found in the ranges of 24.1-53.3%, 15.5-50.3%, and 14.3-50.2% of total fatty acids, respectively. The trans-fatty acid content of Greek margarines varied from 0.1 to 19% and was, on the average, lower than previously reported. The high content in saturated fatty acids of the samples examined is criticized. There is significant discrepancy between fatty acid composition and the description of the product on the label. A concise index to describe fatty acid composition is proposed. This index can appear on the label and would give the consumers a much more accurate picture of the fatty acid composition.


Trebble, T., N. K. Arden, et al. (2003). "Inhibition of tumour necrosis factor-alpha and interleukin 6 production by mononuclear cells following dietary fish-oil supplementation in healthy men and response to antioxidant co-supplementation." Br J Nutr 90(2): 405-12.

            Increased dietary consumption of the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (20 : 5n-3; EPA) and docosahexaenoic acid (22 : 6n-6; DHA) is associated with their incorporation into circulating phospholipid and increased production of lipid peroxide metabolites. The relationship between peripheral blood mononuclear cell (PBMC) function, n-3 PUFA intake and antioxidant co-supplementation is poorly defined. We therefore investigated tumour necrosis factor (TNF)-alpha and interleukin (IL) 6 production by PBMC and phospholipid fatty acid composition in plasma and erythrocytes of healthy male subjects (n 16) receiving supplemental intakes of 0.3, 1.0 and 2.0 g EPA+DHA/d, as consecutive 4-week courses. All subjects were randomised in a double-blind manner to receive a concurrent antioxidant supplement (200 microg Se, 3 mg Mn, 30 mg D-alpha-tocopheryl succinate, 90 mg ascorbic acid, 450 microg vitamin A (beta-carotene and retinol)) or placebo. There was a positive dose-dependent relationship between dietary n-3 PUFA intake and EPA and DHA incorporation into plasma phosphatidylcholine and erythrocyte phosphatidylethanolamine, with a tendency towards a plateau at higher levels of intake. Production of TNF-alpha and IL-6 by PBMC decreased with increasing n-3 PUFA intake but tended towards a 'U-shaped' dose response. Both responses appeared to be augmented by antioxidant co-supplementation at intermediate supplementary n-3 PUFA intakes. Thus, increased dietary n-3 PUFA consumption resulted in defined but contrasting patterns of modulation of phospholipid fatty acid composition and PBMC function, which were further influenced by antioxidant intake.


Tonon, T., D. Harvey, et al. (2003). "Identification of a very long chain polyunsaturated fatty acid Delta4-desaturase from the microalga Pavlova lutheri." FEBS Lett 553(3): 440-4.

            Pavlova lutheri, a marine microalga, is rich in the very long chain polyunsaturated fatty acids (VLCPUFAs) eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids. Using an expressed sequence tag approach, we isolated a cDNA designated Pldes1, and encoding an amino acid sequence showing high similarity with polyunsaturated fatty acid front-end desaturases. Heterologous expression in yeast demonstrated that PlDES1 desaturated 22:5n-3 and 22:4n-6 into 22:6n-3 and 22:5n-6 respectively, and was equally active on both substrates. Thus, PlDES1 is a novel VLCPUFA Delta4-desaturase. Pldes1 expression is four-fold higher during the mid-exponential phase of growth compared to late exponential and stationary phases.


Tokudome, Y., K. Kuriki, et al. (2003). "Seasonal variation in consumption and plasma concentrations of fatty acids in Japanese female dietitians." Eur J Epidemiol 18(10): 945-53.

            OBJECTIVE: To study seasonal variation in intake and plasma concentrations of fatty acids (FAs) in Japanese female dietitians. SUBJECTS AND METHODS: We assessed consumption of FAs based on four season 7 consecutive day weighed diet records from 71 Japanese female dietitians in 1996-1997. Using overnight fasting venous blood, plasma concentrations of FAs were analyzed by gas chromatography. Seasonal variation in consumption and plasma concentrations was examined by ANOVA for repeated values, followed by Tukey's multiple t-test. We calculated Spearman's partial rank correlation coefficients (CCs) between intake and plasma concentrations of FAs. Furthermore, we computed inter-seasonal Spearman's partial rank CCs for consumption and plasma concentrations of FAs. RESULTS: Statistically significant seasonal differences were observed in consumption for most FAs, except for myristic acid, monounsaturated FAs, oleic acid, n-6 polyunsaturated FAs (PUFAs), linoleic acid, gamma-linolenic acid, alpha-linolenic acid, PUFAs/saturated FAs, and n-6 PUFAs/n-3 PUFAs, and for most plasma concentrations, except for stearic acid, gamma-linolenic acid, n-3 PUFAs, alpha-linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and n-3 highly unsaturated FAs (HUFAs). However, statistically significant Spearman's partial rank CCs between intake and plasma concentrations were observed for EPA, DHA, n-3 HUFAs, n-6 PUFAs/n-3 PUFAs and n-6 PUFAs/n-3 HUFAs for almost all seasons. CONCLUSIONS: Seasonal variation exists in consumption and plasma concentrations of FAs, so that this should be taken into account in epidemiological analyses, including case-control and cohort studies.


Togni, V., C. C. Ota, et al. (2003). "Cancer cachexia and tumor growth reduction in Walker 256 tumor-bearing rats supplemented with N-3 polyunsaturated fatty acids for one generation." Nutr Cancer 46(1): 52-8.

            In this study we investigated the effect of lifelong supplementation of the diet with coconut oil (CO, rich in saturated fatty acids) or fish oil (FO, rich in n-3 polyunsaturated fatty acids, PUFAs) on tumor growth, animal survival, and metabolic indicators of cachexia in adult rats. Female Wistar rats were supplemented with CO or FO prior to mating and then throughout pregnancy and gestation, and then the male offspring were supplemented from weaning until 90 days of age. Then they were inoculated subcutaneously with Walker 256 tumor cells. Tumor weight at 14 days in control rats (those fed standard chow) was approximately 20 g. These animals displayed cancer cachexia, which was characterized by loss of weight, hypoglycemia, hyperlacticidemia, hypertriacylglycerolemia, and depletion of glycogen stores. Supplementation of the diet with CO did not change these parameters, except that there was a smaller decrease in serum triacylglycerol concentration. Supplementation of the diet with FO significantly decreased tumor growth (by approximately 60%), increased survival (50% at 30 days postinoculation vs. 30% in the controls and 13.5% in the CO group), and prevented the fall in body weight. Furthermore, FO supplementation partly abolished the fall in serum glucose, totally prevented the elevation in serum lactate concentrations, partly prevented the hypertriacylgylcerolemia, and preserved tissue glycogen stores. Lifelong consumption of FO, rich in n-3 PUFAs, protects against tumor growth and cancer cachexia and improves survival.


Tiemeier, H., H. R. van Tuijl, et al. (2003). "Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam Study." Am J Clin Nutr 78(1): 40-6.

            BACKGROUND: It has been hypothesized that n-3 polyunsaturated fatty acids (PUFAs) are involved in mood regulation, but epidemiologic evidence for such a link in the general population is lacking. OBJECTIVE: This study examined whether community-dwelling elderly persons with depression have a fatty acid composition that is different from that of nondepressed persons. DESIGN: We screened 3884 adults aged > or = 60 y for depressive symptoms as part of the Rotterdam Study. Subjects who screened positive had a psychiatric interview to diagnose depressive disorders. All eligible subjects had their blood drawn for measurement of plasma phospholipid concentrations. We compared percentages of n-3 and n-6 PUFAs and their ratios between 264 subjects with depressive symptoms, including 106 subjects with depressive disorders, and 461 randomly selected reference subjects. We also investigated whether atherosclerosis or the inflammatory response as measured by C-reactive protein underlies the relation between fatty acid composition and depression. RESULTS: Subjects with depressive disorders had a higher ratio of n-6 to n-3 PUFAs, but differences in individual PUFAs were mostly small. However, depressed subjects with normal CRP concentrations (< 1.5 mg/L) had a substantially altered fatty acid composition; percentages of n-3 PUFAs and ratios of n-6 to n-3 PUFAs were significantly lower and higher, respectively, in subjects with depressive disorders than in control subjects [5.2% compared with 5.9% (P = 0.02) and 7.2 compared with 6.6 (P = 0.01), respectively]. This relation was not due to atherosclerosis. CONCLUSIONS: In community-dwelling persons, fatty acid composition is related to depression. Because this relation was not secondary to inflammation, atherosclerosis, or possible confounders, it suggests a direct effect of fatty acid composition on mood.


Thiesen, A. L., K. A. Tappenden, et al. (2003). "Dietary lipids alter the effect of steroids on the transport of glucose after intestinal resection: Part I. Phenotypic changes and expression of transporters." J Pediatr Surg 38(2): 150-60.

            BACKGROUND/PURPOSE: Glucocorticosteroids alter the function of the intestine. This study was undertaken to assess the effect on D-glucose uptake of budesonide (Bud), prednisone (Pred), or dexamethasone (Dex) in animals with a 50% intestinal resection and fed chow or a diet enriched with saturated (SFA) or polyunsaturated fatty acids (PUFA). METHODS: In vitro ring uptake technique, Western blots, and Northern blots were performed. RESULTS: Bud increased the jejunal D-glucose uptake, and this effect was prevented by feeding PUFA. SGLT1 and Na+/K+ ATPase protein and mRNA abundance did not correlate with the change in the rate of uptake of glucose. CONCLUSIONS: (1) Bud increased the jejunal glucose uptake, (2) the activity of the sugar transporter does not correlate with the abundance of protein or their respective mRNAs, (3) th Bud effect on glucose uptake is prevented by feeding PUFA. Thus, the desired intestinal adaptive response after intestinal resection may be enhanced further by the administration of the locally acting steroid budesonide and by feeding a saturated compared with a polyunsaturated fatty acid diet.


Thiesen, A. L., K. A. Tappenden, et al. (2003). "Dietary lipids alter the effect of steroids on transport of glucose after intestinal resection: Part II. Signalling of the response." J Pediatr Surg 38(4): 575-8.

            BACKGROUND/PURPOSE: Glucocorticosteroids alter the function of the intestine. Budesonide (Bud) increases the jejunal D-glucose uptake, and this effect is prevented through a polyunsaturated fatty acid (PUFA) diet. This study was undertaken to assess the possible signalling effect of budesonide, prednisone (Pred), or dexamethasone (Dex) in animals with a 50% intestinal resection and fed chow or a diet enriched with saturated (SFA) or polyunsaturated fatty acids. METHODS: Northern blots were performed. RESULTS: Steroids reduced the jejunal but not the ileal expression of proglucagon. Ornithine decarboxylase (ODC) expression was reduced in the jejunum. CONCLUSIONS: c-jun, ODC, and proglucagon may be involved in the adaptive response that occurs with steroids and variations in dietary lipids after intestinal resection.


Thiesen, A., M. Keelan, et al. (2003). "Effect of steroids on intestinal lipid uptake in rats is enhanced by a saturated Fatty Acid diet. Cell and molecular biology collaborative network in gastrointestinal physiology." Digestion 68(2-3): 109-18.

            Glucocorticosteroids enhance sugar digestive and absorptive functions of the intestine, but their effect on lipid uptake is unknown. Modifications in dietary lipids alter the nutrient transport properties of the intestine. The influence of 4 weeks' treatment with budesonide (BUD), prednisone (PRED), or control vehicle in weanling rats fed either an isocaloric semisynthetic saturated fatty acid diet (SFA) or a polyunsaturated fatty acid diet (PUFA), on the uptake of lipids was assessed using everted gut rings. PRED and BUD increased the uptake of several fatty acids, and this was higher when the animals were fed SFA rather than PUFA. Changes in expression of the mRNAs for L-FABP (liver fatty acid binding protein) and ILBP (ileal lipid binding protein) did not explain these alterations in lipid uptake. Dietary lipid signalling of this adaptive response may involve proglucagon, c-jun, TNF-alpha and IL-10, whereas steroid signalling may involve proglucagon. In summary, steroids increase the absorption of lipids by a process which can be enhanced by the substitution of saturated for polyunsaturated lipids in the diet, and which is not explained by alterations in the expression of the mRNAs of L-FABP or ILBP.


Thies, F., J. M. Garry, et al. (2003). "Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial." Lancet 361(9356): 477-85.

            BACKGROUND: N-3 polyunsaturated fatty acids (PUFAs) from oily fish protect against death from cardiovascular disease. We aimed to assess the hypothesis that incorporation of n-3 and n-6 PUFAs into advanced atherosclerotic plaques increases and decreases plaque stability, respectively. METHODS: We did a randomised controlled trial of patients awaiting carotid endarterectomy. We randomly allocated patients control, sunflower oil (n-6), or fish-oil (n-3) capsules until surgery. Primary outcome was plaque morphology indicative of stability or instability, and outcome measures were concentrations of EPA, DHA, and linoleic acid in carotid plaques; plaque morphology; and presence of macrophages in plaques. Analysis was per protocol. FINDINGS: 188 patients were enrolled and randomised; 18 withdrew and eight were excluded. Duration of oil treatment was 7-189 days (median 42) and did not differ between groups. The proportions of EPA and DHA were higher in carotid plaque fractions in patients receiving fish oil compared with those receiving control (absolute difference 0.5 [95% CI 0.3-0.7], 0.4 [0.1-0.6], and 0.2 [0.1-0.4] g/100 g total fatty acids for EPA; and 0.3 [0.0-0.8], 0.4 [0.1-0.7], and 0.3 [0.1-0.6] g/100 g total fatty acids for DHA; in plaque phospholipids, cholesteryl esters, and triacylglycerols, respectively). Sunflower oil had little effect on the fatty acid composition of lipid fractions. Fewer plaques from patients being treated with fish oil had thin fibrous caps and signs of inflammation and more plaques had thick fibrous caps and no signs of inflammation, compared with plaques in patients in the control and sunflower oil groups (odds ratio 0.52 [95% CI 0.24-0.89] and 1.19 [1.02-1.57] vs control; 0.49 [0.23-0.90] and 1.16 [1.01-1.53] vs sunflower oil). The number of macrophages in plaques from patients receiving fish oil was lower than in the other two groups. Carotid plaque morphology and infiltration by macrophages did not differ between control and sunflower oil groups. INTERPRETATION: Atherosclerotic plaques readily incorporate n-3 PUFAs from fish-oil supplementation, inducing changes that can enhance stability of atherosclerotic plaques. By contrast, increased consumption of n-6 PUFAs does not affect carotid plaque fatty-acid composition or stability over the time course studied here. Stability of plaques could explain reductions in non-fatal and fatal cardiovascular events associated with increased n-3 PUFA intake.


Thibault, C., D. Petitclerc, et al. (2003). "Effect of feeding prepubertal heifers with a high oil diet on mammary development and milk production." J Dairy Sci 86(7): 2320-6.

            The objective of this study was to evaluate the effect of feeding prepubertal heifers a diet containing a high level of polyunsaturated fatty acids on mammary development and milk production. A total of 116 Holstein heifers were either fed a conventionally formulated concentrate or a high oil (HO) concentrate, using the same formulation but including 20% soybean oil, from birth to 6 mo of age. After 6 mo of age, all heifers were managed identically. Mammary gland development was evaluated on heifers slaughtered at 4 mo (n = 10) and 12 mo (n = 30) of age. Other heifers were bred when they reached 15 mo of age and milk production and feed intake were recorded every day from wk 4 to 18 of lactation. Feeding the high oil concentrate increased the concentration of linoleic acid in blood plasma (176%) and mammary fat pad (78%) at 4 mo of age and mammary fat pad (93%) at 12 mo of age. At 4 mo of age, mammary development was similar in both treatments. At 12 mo of age, total, parenchyma, and stroma weights of the mammary gland were not affected by treatments. However, lipid content was lower and concentration of DNA was higher in the parenchyma of heifers fed the high oil diet. Nevertheless, total parenchymal DNA and dry fat free tissue content did not reach statistical significance despite the fact that they were, respectively, 15 and 21% higher in HO heifers. Milk production and composition was not affected by treatments. In conclusion, feeding prepubertal heifers with a high oil concentrate slightly improved the mammary development but effects were too small to be translated into better lactating performances.


Tavani, A., C. Pelucchi, et al. (2003). "n-3 polyunsaturated fatty acid intake and cancer risk in Italy and Switzerland." Int J Cancer 105(1): 113-6.

            Data from a series of case-control studies, conducted in Italy and Switzerland between 1991 and 2001, have been analyzed to evaluate the role of n-3 polyunsaturated fatty acid (PUFA) intake in the etiology of cancer of oral cavity and pharynx (736 cases, 1772 controls), esophagus (395 cases, 1066 controls), large bowel (1394 colon, 886 rectum, 4765 controls), breast (2900 cases, 3122 controls) and ovary (1031 cases, 2411 controls). Controls were patients admitted to hospital for acute, non-neoplastic conditions, unrelated to modifications in diet. The multivariate odds ratios (OR) for the highest quintile of n-3 PUFAs compared to the lowest one were 0.5 for oral and pharyngeal cancer, 0.5 for oesophageal cancer, 0.7 for colon cancer, 0.8 for rectal and breast cancer and 0.6 for ovarian cancer; the estimates and the trends in risk were significant for all cancer sites, excluding rectal and breast cancer. The estimates for an increase in n-3 PUFAs of 1 g/week were 0.70 for oral and pharyngeal cancer, 0.71 for oesophageal, 0.88 for colon, 0.91 for rectal, 0.90 for breast and 0.85 for ovarian cancer. All the estimates were statistically significant, excluding that for rectal cancer, and consistent across strata of age and gender. These results suggest that n-3 PUFAs decrease the risk of several cancers.


Tanaka, T., D. Iwawaki, et al. (2003). "Mechanisms of accumulation of arachidonate in phosphatidylinositol in yellowtail. A comparative study of acylation systems of phospholipids in rat and the fish species Seriola quinqueradiata." Eur J Biochem 270(7): 1466-73.

            It is known that phosphatidylinositol (PtdIns) contains abundant arachidonate and is composed mainly of 1-stearoyl-2-arachidonoyl species in mammals. We investigated if this characteristic of PtdIns applies to the PtdIns from yellowtail (Seriola quinqueradiata), a marine fish. In common with phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn) and phosphatidylserine (PtdSer) from brain, heart, liver, spleen, kidney and ovary, the predominant polyunsaturated fatty acid was docosahexaenoic acid, and levels of arachidonic acid were less than 4.5% (PtdCho), 7.5% (PtdEtn) and 3.0% (PtdSer) in these tissues. In striking contrast, arachidonic acid made up 17.6%, 31.8%, 27.8%, 26.1%, 25.4% and 33.5% of the fatty acid composition of PtdIns from brain, heart, liver, spleen, kidney and ovary, respectively. The most abundant molecular species of PtdIns in all these tissues was 1-stearoyl-2-arachidonoyl. Assay of acyltransferase in liver microsomes of yellowtail showed that arachidonic acid was incorporated into PtdIns more effectively than docosahexaenoic acid and that the latter inhibited incorporation of arachidonic acid into PtdCho without inhibiting the utilization of arachidonic acid for PtdIns. This effect of docosahexaenoic acid was not observed in similar experiments using rat liver microsomes and is thought to contribute to the exclusive utilization of arachidonic acid for acylation to PtdIns in yellowtail. Inositolphospholipids and their hydrolysates are known to act as signaling molecules in cells. The conserved hydrophobic structure of PtdIns (the 1-stearoyl-2-arachidonoyl moiety) may have physiological significance not only in mammals but also in fish.


Tanaka, Y., M. Hashimoto, et al. (2003). "Effects of exercise on platelet and aortic functions in aged rats." Acta Physiol Scand 179(2): 155-65.

            AIM AND METHODS: To assess age- and exercise-related changes in platelet aggregation, we measured the magnitude of platelet aggregation with a four-channel aggregometer, plasma and aortic polyunsaturated fatty acids by gas chromatography and related prostanoids with a reagent kit in young and aged non-exercised and in aged exercised rats. RESULTS: Platelet aggregation in platelet-rich plasma induced by ADP (5 microm) in the primary wave increased with age. In the non-exercised groups, the basal levels of thromboxane B2 in platelet-rich plasma increased in aged rats compared with young rats. In aged exercised rats, the basal levels of 6-keto-prostaglandin F1alpha in platelet-rich plasma were stimulated and those of thromboxane B2 were depressed, compared with non-exercised aged rats. The plasma levels of eicosapentaenoic acid and docosahexaenoic acid increased with age. Only aortic eicosapentaenoic acid in the aged group increased by exercise. In the aged non-exercised and exercised groups, the aortic, but not the plasma, levels of eicosapentaenoic acid correlated inversely with the basal levels of thromboxane B2 in platelet-rich plasma (r = -0.53, P < 0.05) and associated negatively with the magnitudes of platelet aggregation induced by ADP (5 microm) (r = -0.47, P < 0.05). CONCLUSION: These findings suggest that exercise in aged rats increases aortic eicosapentaenoic acid concentrations, which in turn depress the basal levels of thromboxane, B2 in platelet-rich plasma to modulate platelet aggregation.


Takezaki, T., M. Inoue, et al. (2003). "Diet and lung cancer risk from a 14-year population-based prospective study in Japan: with special reference to fish consumption." Nutr Cancer 45(2): 160-7.

            N-3 polyunsaturated fatty acids in fish oil exhibit a variety of health benefits, and there is evidence that they can inhibit the development of human lung mucoepidermoid and other carcinomas. To examine the hypothesis that fish consumption reduces the risk of lung cancer, we conducted a population-based prospective study, following 5,885 residents for 14 yr. Person-years were used to calculate the relative risk (RR) by the Cox proportional hazards model, with adjustment for potential confounding factors. A total of 51 incident lung cancer cases were observed, and we found linearly decreasing RRs for lung cancer with increased frequency of consumption of fish and shellfish (RRs = 1.00, 0.99, and 0.32, P for trend = 0.003) but not with intake of dried/salted fish. Decreased RRs were apparent with both broiling and boiling cooking methods, but reduction with raw and deep-fried fish consumption was not statistically significant. We conclude that frequent fresh fish consumption, irrespective of the cooking method, may reduce the risk of lung cancer.


Takahashi, Y., M. Kushiro, et al. (2003). "Activity and mRNA levels of enzymes involved in hepatic fatty acid synthesis and oxidation in mice fed conjugated linoleic acid." Biochim Biophys Acta 1631(3): 265-73.

            The effects of dietary conjugated linoleic acid (CLA) on the activity and mRNA levels of hepatic enzymes involved in fatty acid synthesis and oxidation were examined in mice. In the first experiment, male ICR and C57BL/6J mice were fed diets containing either a 1.5% fatty acid preparation rich in CLA or a preparation rich in linoleic acid. In the second experiment, male ICR mice were fed diets containing either 1.5% linoleic acid, palmitic acid or the CLA preparation. After 21 days, CLA relative to linoleic acid greatly decreased white adipose tissue mass but caused hepatomegaly accompanying an approximate 10-fold increase in the tissue triacylglycerol content irrespective of mouse strain. CLA compared to linoleic acid greatly increased the activity and mRNA levels of various lipogenic enzymes in both experiments. Moreover, CLA increased the mRNA expression of Delta6- and Delta5-desaturases, and sterol regulatory element binding protein-1 (SREBP-1). The mitochondrial and peroxisomal palmitoyl-CoA oxidation rate was about 2.5-fold higher in mice fed CLA than in those fed linoleic acid in both experiments. The increase was associated with the up-regulation of the activity and mRNA expression of various fatty acid oxidation enzymes. The palmitic acid diet compared to the linoleic acid diet was rather ineffective in modulating the hepatic lipid levels or activity and mRNA levels of enzymes in fatty acid metabolism. It is apparent that dietary CLA concomitantly increases the activity and mRNA levels of enzymes involved in fatty acid synthesis and oxidation, and desaturation of polyunsaturated fatty acid in the mouse liver. Both the activation of peroxisomal proliferator alpha and up-regulation of SREBP-1 may be responsible for this.


Tacikowski, T., B. Wajszczyk, et al. (2003). "[In Process Citation]." Pol Merkuriusz Lek 15(86): 168-71.

            STUDY AIM: Analysis of differences in fat consumption (total fat, saturated, monounsaturated and polyunsaturated acids) and cholesterol between patients with large adenomas (study group, GB) and control group (GK). MATERIAL AND METHODS: GB and GK patients were recruited from the patients undergoing full colonoscopy during routine work of endoscopy unit. The whole material included 111 patients: 57 patients with large bowel adenomas and 54 without large bowel adenomas. The intake of fat was assessed using a method calculating intake during 30 days preceding the study. RESULTS: In the group of studied women versus control group women no significant differences were found in consumption including energy value of diet (1755.8 kcal vs 1925.0 kcal), total protein (69.1 g vs 76.1 g), carbohydrates (237.2 g vs 258.0 g). Similarly, in the group of studied men no significant differences were found in the consumption of total protein (84.6 g), carbohydrates (275.7 g) and energy (2126.9 kcal) in relation to control group in which the respective values were: 98.4 g, 336.1 g and 2612.8 kcal. In the group of studied women the mean fat consumption was 67.2 g while in the control group it was 73.4 g. The mean intake of saturated fatty acids was 24.0 g and 25.2 g respectively. The consumption of monounsaturated and polyunsaturated fatty acids was in these group 27.1 g and 10.5 g vs 30.5 g and 11.9 g. The differences were statistically not significant. No difference was found in cholesterol intake between women in the study group and those in control group (245.8 mg and 280.0 mg respectively). The male study group was not differing significantly from the control group in the consumption of total fat (83.6 g vs 102.3 g), saturated fatty acids (29.7 g vs 37.5 g), monounsaturated and polyunsaturated fatty acids (34.2 g vs 42.1 and 13.0 g 14.7 g) and cholesterol (335.0 mg vs 420.4 mg). CONCLUSION: No correlation was found between the consumption of total fat, saturates, monounsaturated and polyunsaturated fatty acids and the occurrence of large bowel adenomas.


Szymczyk, B. and P. M. Pisulewski (2003). "Effects of dietary conjugated linoleic acid on fatty acid composition and cholesterol content of hen egg yolks." Br J Nutr 90(1): 93-9.

            The main objectives of the present study were to determine the effect of dietary conjugated linoleic acid (CLA) isomers on the fatty acid composition and cholesterol content of egg-yolk lipids. Forty-five 25-week-old laying hens were randomly distributed into five groups of nine hens each and maintained in individual laying cages, throughout 12 weeks of the experiment. They were assigned to the five treatments that consisted of commercial layer diets containing 0, 5, 10, 15 or 20 g pure CLA/kg. Feed intake of hens varied little and insignificantly. Egg mass was uniformly lower (P<0.05) in the hens fed the CLA-enriched diets. Feed conversion efficiency, when expressed per kg eggs, was impaired (P<0.05), although without obvious relation to the dietary CLA concentration. Feeding the CLA-enriched diets resulted in gradually increasing deposition of CLA isomers (P<0.01) in egg-yolk lipids. Saturated fatty acids were increased (P<0.01) and monounsaturated fatty acids decreased (P<0.01). Polyunsaturated fatty acids (PUFA), when expressed as non-CLA PUFA, were also significantly decreased (P<0.01). The most striking effects (P<0.01) were observed for palmitic (16 : 0) and stearic (18 : 0) acids, which increased from 23.6 to 34 % and from 7.8 to 18 %, respectively. On the other hand, oleic acid (18 : 1n-9) decreased from 45.8 to 24.3 %. Among non-CLA PUFA, linoleic (18 : 2n-6) and alpha-linolenic (18 : 3n-3) acids were strongly (P<0.01) decreased, from 14.2 to 7.7 % and from 1.3 to 0.3 %, respectively. The same was true for arachidonic (20:4n-6) and docosahexaenoic (22 : 6n-3) acids. The cholesterol content of egg yolks, when expressed in mg/g yolk, was not affected by the dietary CLA concentrations. In conclusion, unless the adverse effects of CLA feeding to laying hens on the fatty acid profile of egg yolks are eliminated, the CLA-enriched eggs cannot be considered functional food products.


Szostak, W. B., W. Sekula, et al. (2003). "Reduction of cardiovascular mortality in Poland and changes in dietary patterns." Kardiol Pol 58(3): 173-81; discussion 180-1.

            BACKGROUND. A decrease in mortality due to cardiovascular diseases has been recently documented in Poland. AIM. To assess changes in dietary patterns in Poland in the 90's. METHODS. The Central Statistical Office data on food consumption from the years 1989-2000 were analysed. The energy and fatty acid content in the consumed food were calculated with the use of the national food composition tables. RESULTS. A decrease in the consumption of butter by 52%, other animal fats by 20%, milk by 27%, beef by 57% and potatoes by 8% was noted. On the other hand, the consumption of vegetable fat increased by 100%, poultry by 70% and fruit by 64%. Changes in the consumption of cereal products, vegetables, pork, eggs and sugar were insignificant. A decrease of 19% in the consumption of saturated fatty acids and an increase of 32% in the intake of the polyunsaturated fatty acids were found. CONCLUSIONS. Changes in dietary patterns explain, at least in part, a marked reduction in cardiovascular mortality recently observed in Poland.


Szabo, J., W. H. Ibrahim, et al. (2003). "Effect of dietary protein quality and essential fatty acids on fatty acid composition in the liver and adipose tissue after rapid weight loss in overweight cats." Am J Vet Res 64(3): 310-5.

            OBJECTIVE: To examine effects of dietary protein quality (casein [CA] vs corn gluten [CG]) and dietary lipids (corn oil [CO] vs oil blend [OB] rich in long-chain polyunsaturated fatty acids [LCPUFAs]) on fatty acid composition in liver and adipose tissue after weight loss in overweight cats. ANIMALS: 24 ovariohysterectomized adult cats. PROCEDURE: Cats were allowed ad libitum access to a high-quality diet until they weighed 30% more than their ideal body weight. Cats were then randomly assigned to 1 of 4 weight-reduction diets (6 cats/diet) and were fed 25% of maintenance energy requirements per day. Diets consisted of CG-CO, CA-CO, CG-OB, and CA-OB, respectively, and were fed until cats lost weight and returned to their original lean body mass. Liver biopsy specimens and samples of perirenal, subcutaneous, and abdominal fat were obtained and analyzed for fatty acid content. RESULTS: Following weight loss, fatty acid composition of the liver and adipose tissue was primarily affected by protein quality in that cats fed CA had significantly higher percentages of 20:4(n-6) and 22:6(n-3) fatty acids than those fed CG. Cats fed the CG-CO diet had the lowest concentrations of LCPUFAs, suggesting that dietary lipids and protein quality each influence fatty acid composition in tissues. CONCLUSIONS AND CLINICAL RELEVANCE: These data provide direct evidence that dietary protein quality alters fatty acid composition of tissues during weight loss in cats. The fatty acid patterns observed suggest that protein quality may alter fatty acid composition through modulation of desaturase activity.


Switzer, K. C., D. N. McMurray, et al. (2003). "(n-3) Polyunsaturated fatty acids promote activation-induced cell death in murine T lymphocytes." J Nutr 133(2): 496-503.

            Previous studies showing dietary (n-3) polyunsaturated fatty acids (PUFA) attenuate T cell immune-mediated inflammatory diseases led us to hypothesize that (n-3) PUFA promote activation-induced cell death (AICD) in T cells. Because T cell subsets display a differential resistance to AICD, we compared the effects of (n-3) PUFA feeding on T cells stimulated in vitro to express different cytokine profiles. Mice were fed either diets lacking (n-3) PUFA (control) or (n-3) PUFA-containing diets for 14 d. Splenic T cells were stimulated with alphaCD3/alphaCD28, phorbol myristate acetate (PMA)/Ionomycin or alphaCD3/PMA for 48 h, followed by reactivation with the same stimuli for 5 h. Apoptosis was measured using Annexin V/propidium iodide. (n-3) PUFA were selectively incorporated into membrane phospholipid pools. Cytokine analyses revealed that (n-3) PUFA enhanced AICD only in T cells expressing a T helper cell (Th)1-like cytokine profile after stimulation with PMA/Ionomycin compared to mice fed the (n-6) PUFA control diet (P = 0.0008). In contrast, no increase in apoptosis was seen in T cells stimulated with alphaCD3/PMA, which exhibited a Th2 cytokine profile. These data demonstrate that the ability of (n-3) PUFA to promote AICD is dependent on the activation stimulus. In conclusion, we have identified a novel mechanism by which (n-3) PUFA modulate T cell-mediated immunity by selective deletion of Th1-like cells while maintaining or enhancing the Th2-mediated humoral immune response.


Swan, J. S., K. Dibb, et al. (2003). "Effects of eicosapentaenoic acid on cardiac SR Ca(2+)-release and ryanodine receptor function." Cardiovasc Res 60(2): 337-46.

            n-3 polyunsaturated fatty acids (PUFAs) can prevent life-threatening arrhythmias but the mechanisms responsible have not been established. There is strong evidence that part of the antiarrhythmic action of PUFAs is mediated through inhibition of the Ca(2+)-release mechanism of the sarcoplasmic reticulum (SR). It has also been shown that PUFAs activate protein kinase A (PKA) and produce effects in the cardiac cell similar to beta-adrenergic stimulation. We have investigated whether the inhibitory effect of PUFAs on the Ca(2+)-release mechanism is caused by direct inhibition of the SR Ca(2+)-release channel/ryanodine receptor (RyR) or requires activation of PKA. Experiments in intact cells under voltage-clamp show that the n-3 PUFA eicosapentaenoic acid (EPA) is able to reduce the frequency of spontaneous waves of Ca(2+)-release while increasing SR Ca(2+) content even when PKA activity is inhibited with H-89. This suggests that the EPA-induced inhibition of SR Ca(2+)-release is not dependent on activation of PKA. Consistent with this, single-channel studies demonstrate that EPA (10-100 microM), but not saturated fatty acids, reduce the open probability (Po) of the cardiac RyR incorporated into phospholipid bilayers. EPA also inhibited the binding of [3H]ryanodine to isolated heavy SR. Our results indicate that direct inhibition of RyR channel gating by PUFAs play an important role in the overall antiarrhythmic properties of these compounds.


Svensson, S., T. Ostberg, et al. (2003). "Crystal structure of the heterodimeric complex of LXRalpha and RXRbeta ligand-binding domains in a fully agonistic conformation." Embo J 22(18): 4625-33.

            The nuclear receptor heterodimers of liver X receptor (LXR) and retinoid X receptor (RXR) are key transcriptional regulators of genes involved in lipid homeostasis and inflammation. We report the crystal structure of the ligand-binding domains (LBDs) of LXRalpha and RXRbeta complexed to the synthetic LXR agonist T-0901317 and the RXR agonist methoprene acid (Protein Data Base entry 1UHL). Both LBDs are in agonist conformation with GRIP-1 peptides bound at the coactivator binding sites. T-0901317 occupies the center of the LXR ligand-binding pocket and its hydroxyl head group interacts with H421 and W443, residues identified by mutational analysis as critical for ligand-induced transcriptional activation by T-0901317 and various endogenous oxysterols. The topography of the pocket suggests a common anchoring of these oxysterols via their 22-, 24- or 27-hydroxyl group to H421 and W443. Polyunsaturated fatty acids act as LXR antagonists and an E267A mutation was found to enhance their transcriptional inhibition. The present structure provides a powerful tool for the design of novel modulators that can be used to characterize further the physiological functions of the LXR-RXR heterodimer.


Sushchik, N. N., M. I. Gladyshev, et al. (2003). "Comparison of fatty acid composition in major lipid classes of the dominant benthic invertebrates of the Yenisei river." Comp Biochem Physiol B Biochem Mol Biol 134(1): 111-22.

            The composition and content of fatty acids (FAs) in total lipids, triacylglycerols (TAG) and polar lipids (PL) in dominant groups of benthic invertebrates: gammarids (Gammaridae, Amphipoda), chironomid larvae (Chironomidae, Diptera), caddisfly larvae (Trichoptera) and mayfly larvae (Ephemeroptera) were studied in the Yenisei river. For the first time data on the FA composition of species belonging to Trichoptera (Insecta) are presented. The groups of aquatic insect larvae and gammarids weakly differed in total content of essential polyunsaturated fatty acids (PUFAs). Hence, the strong invasion of gammarids which occurred in the last decades in the Yenisei river should not result in a decrease in potential yield of essential PUFA in the ecosystem and corresponding decrease in food resource quality for fish in respect to PUFA content. Significant differences in biomarker FAs in TAG were found which correlated to specific food sources. Different levels of long-chain PUFA in PL of the invertebrates are discussed in relation to the genetic ability of particular taxa to form these FAs.


Surh, J., J. S. Ryu, et al. (2003). "Seasonal variations of fatty acid compositions in various Korean shellfish." J Agric Food Chem 51(6): 1617-22.

            Seasonal variations of fatty acids in various Korean shellfish were investigated in relation to the changes in total fatty acids contents, the ratio of polyunsaturated fatty acids to saturated fatty acids (P/S), and that of n-3 fatty acids to n-6 fatty acids (n-3/n-6). A distinct seasonal pattern was found in total fatty acids contents with maximal values in early summer and minimal values in late summer. The percentage of monounsaturated fatty acids was lowest in most species throughout the year. In summer months, the proportion of polyunsaturated fatty acids decreased while that of saturated fatty acids increased. The major contributing factor to the seasonal variation of polyunsaturated fatty acids was n-3 fatty acids. These results led to the lowest levels of P/S and n-3/n-6 in summer. Nevertheless, the data suggest that bivalve shellfish would be excellent sources of n-3 fatty acids, especially eicosapentaenoic acid and docosahexaenoic acid.


Surette, M. E., I. L. Koumenis, et al. (2003). "Inhibition of leukotriene synthesis, pharmacokinetics, and tolerability of a novel dietary fatty acid formulation in healthy adult subjects." Clin Ther 25(3): 948-71.

            BACKGROUND: Numerous studies have explored dietary-management strategies for decreasing leukotriene synthesis by inflammatory cells through supplementation with polyunsaturated fatty acids such as gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA). OBJECTIVES: This study sought to determine the optimal daily intake, ratios, and formulation of dietary GLA and EPA required to safely reduce leukotriene biosynthesis in healthy individuals, and to evaluate the pharmacokinetics and safety profile of such a formulation. METHODS: Two preliminary trials were conducted to determine the minimum effective levels of GLA and EPA intake needed to reduce leukotriene biosynthesis and prevent increases in plasma arachidonic acid (AA) concentrations. These preliminary trials were followed by a single-center, randomized, double-blind, placebo-controlled, parallel-group, escalating-intake inpatient trial of a dietary GLA/EPA emulsion (PLT 3514) in healthy adult subjects. Subjects consumed either 10, 20, or 100 g of the PLT 3514 emulsion (respectively containing 0.75 g GLA + 0.5 g EPA, 1.5 g GLA + 1 g EPA, and 7.5 g GLA + 5 g EPA), or a placebo emulsion containing olive oil daily for 14 days. Plasma fatty acids were measured by gas chromatography Stimulated whole blood leukotrienes were measured by high-performance liquid chromatography with ultraviolet detection. RESULTS: Thirty subjects were included in the preliminary trials; 47 subjects were enrolled in the escalating-intake trial, of whom 42 completed the study. In the preliminary trials, intake of GLA 1.5 g/d in gelatin capsules decreased the capacity to synthesize leukotrienes but increased plasma levels of AA (both, P < 0.05). Inclusion of 0.25 or 1 g of dietary EPA prevented the increase in plasma AA concentrations. Dietary GLA and EPA showed significantly enhanced bioavailability when consumed in 20 g PLT 3514 emulsion compared with consumption in gelatin capsules (P < 0.05), resulting in a reduction in the amount of intake required to block leukotriene biosynthesis. Pharmacokinetic analyses indicated that fasting plasma GLA and EPA levels plateaued within 7 days' daily consumption at all levels of intake, whereas the time to maximum plasma concentration (Tmax) was shorter for GLA than for EPA. The Tmax was similar on days 1 and 14 for both GLA and EPA. There were no clinically significant between-group differences in changes in vital signs, mean clinical laboratory values, or abbreviated hematology laboratory tests, or significant differences in the occurrence of treatment-emergent adverse events between the group consuming up to 20 g/d of the GLA/EPA emulsion and the group consuming placebo. CONCLUSION: Consumption of specific proportions and intake levels of dietary GLA and EPA in a novel emulsion formulation inhibited leukotriene biosynthesis and appeared to be well tolerated in this population of healthy adult subjects.


Surette, M. E., I. L. Koumenis, et al. (2003). "Inhibition of leukotriene biosynthesis by a novel dietary fatty acid formulation in patients with atopic asthma: a randomized, placebo-controlled, parallel-group, prospective trial." Clin Ther 25(3): 972-9.

            BACKGROUND: Leukotriene inhibitors and leukotriene-receptor antagonists are effective in the treatment of inflammatory diseases such as asthma. A search of the entirety of MEDLINE using the terms diet plus leukotrienes identified numerous studies that have explored dietary-management strategies to reduce leukotriene levels through supplementation with polyunsaturated fatty acids such as gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA). However, the search found no studies on the use of combinations of these fatty acids in patients with asthma. OBJECTIVE: The goal of this study was to determine the effect of daily intake of an emulsion (PLT 3514) containing dietary GLA and EPA on ex vivo stimulated whole blood leukotriene biosynthesis in patients with atopic asthma. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group, prospective trial in patients with mild to moderate atopic asthma. Patients consumed 10 g PLT 3514 emulsion (containing 0.75 g GLA + 0.5 g EPA), 15 g PLT 3514 emulsion (containing 1.13 g GLA + 0.75 g EPA), or placebo (olive oil) emulsion daily for 4 weeks. Plasma fatty acids were measured by gas chromatography, and stimulated whole blood leukotrienes were measured by reverse-phase high-performance liquid chromatography with ultraviolet detection using a diode array detector. RESULTS: Forty-three patients (33 women, 10 men) participated in the study. Leukotriene biosynthesis was significantly decreased in patients consuming 10 or 15 g PLT 3514 compared with placebo (P < 0.05, analysis of covariance). No clinically significant changes in vital signs were observed throughout the study, and there were no significant between-group differences in treatment-emergent adverse events or mean clinical laboratory values. CONCLUSION: Daily consumption of dietary GLA and EPA in a novel emulsion formulation inhibited leukotriene biosynthesis in this population of patients with atopic asthma and was well tolerated.


Suresh, Y. and U. N. Das (2003). "Long-chain polyunsaturated fatty acids and chemically induced diabetes mellitus: effect of omega-6 fatty acids." Nutrition 19(2): 93-114.

            OBJECTIVE: We previously showed that prior oral supplementation of oils rich in omega-3, eicosapentaenoic acid and docosahexaenoic acid, and omega-6, gamma-linolenic acid and arachidonic acid, can prevent the development of alloxan-induced diabetes mellitus in experimental animals. But the effect of individual fatty acids on chemically induced diabetes mellitus is not known. We report the results of our studies with omega-6 fatty acids. METHODS: Alloxan-induced in vitro cytotoxicity and apoptosis in an insulin-secreting rat insulinoma cell line, RIN, was prevented by prior exposure of these cells to linoleic acid, gamma-linolenic acid, and arachidonic acid (AA) but not to dihomo-gamma-linolenic acid. Cyclo-oxygenase and lipoxygenase inhibitors did not block this protective action of AA. Prior oral supplementation with gamma-linolenic acid and pre- and simultaneous treatments with AA prevented alloxan-induced diabetes mellitus. RESULTS: Even though pretreatment with linoleic acid and dihomo-gamma-linolenic acid and simultaneous treatment with linoleic acid, gamma-linolenic acid, and dihomo-gamma-linolenic acid did not prevent the development of diabetes mellitus, the severity of diabetes was much less. The saturated fatty acid stearic acid and the monounsaturated fatty acid oleic acid were ineffective in preventing alloxan-induced diabetes mellitus. gamma-Linolenic acid and AA not only attenuated chemically induced diabetes mellitus but also restored the antioxidant status to normal range in various tissues. Changes in the concentrations of various fatty acids of the phospholipid fraction of plasma that occurred as a result of alloxan-induced diabetes mellitus also reverted to normal in the AA-treated animals. CONCLUSIONS: These results suggest that polyunsaturated fatty acids can prevent chemically induced diabetes in experimental animals and attenuate the oxidant stress that occurs in diabetes mellitus.


Suresh, Y. and U. N. Das (2003). "Long-chain polyunsaturated fatty acids and chemically induced diabetes mellitus. Effect of omega-3 fatty acids." Nutrition 19(3): 213-28.

            In a previous study, we showed that prior oral feeding of oils rich in omega-3 eicosapentaenoic acid and docosahexaenoic acid and omega-6 gamma-linolenic acid and arachidonic acid prevent the development of alloxan-induced diabetes mellitus in experimental animals. We also observed that 99% pure omega-6 fatty acids gamma-linolenic acid and arachidonic acid protect against chemically induced diabetes mellitus. Here we report the results of our studies with omega-3 fatty acids. Alloxan-induced in vitro cytotoxicity and apoptosis in an insulin-secreting rat insulinoma cell line, RIN, was prevented by prior exposure of these cells to alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid. Prior oral supplementation with alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid prevented alloxan-induced diabetes mellitus. alpha-Linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid not only attenuated chemical-induced diabetes mellitus but also restored the anti-oxidant status to normal range in various tissues. These results suggested that omega-3 fatty acids can abrogate chemically induced diabetes in experimental animals and attenuate the oxidant stress that occurs in diabetes mellitus.


Sundram, K., M. A. French, et al. (2003). "Exchanging partially hydrogenated fat for palmitic acid in the diet increases LDL-cholesterol and endogenous cholesterol synthesis in normocholesterolemic women." Eur J Nutr 42(4): 188-94.

            Partial hydrogenation of oil results in fats containing unusual isomeric fatty acids characterized by cis and trans configurations. Hydrogenated fats containing trans fatty acids increase plasma total cholesterol (TC) and LDL-cholesterol while depressing HDL-cholesterol levels. Identifying the content of trans fatty acids by food labeling is overshadowed by a reluctance of health authorities to label saturates and trans fatty acids separately. Thus, it is pertinent to compare the effects of trans to saturated fatty acids using stable isotope methodology to establish if the mechanism of increase in TC and LDL-cholesterol is due to the increase in the rate of endogenous synthesis of cholesterol. Ten healthy normocholesterolemic female subjects consumed each of two diets containing approximately 30% of energy as fat for a fourweek period. One diet was high in palmitic acid (10.6% of energy) from palm olein and the other diet exchanged 5.6% of energy as partially hydrogenated fat for palmitic acid. This fat blend resulted in monounsaturated fatty acids decreasing by 4.9 % and polyunsaturated fats increasing by 2.7%. The hydrogenated fat diet treatment provided 3.1% of energy as elaidic acid. For each dietary treatment, the fractional synthesis rates for cholesterol were measured using deuterium-labeling procedures and blood samples were obtained for blood lipid and lipoprotein measurements. Subjects exhibited a higher total cholesterol and LDL-cholesterol level when consuming the diet containing trans fatty acids while also depressing the HDL-cholesterol level. Consuming the partially hydrogenated fat diet treatment increased the fractional synthesis rate of free cholesterol. Consumption of hydrogenated fats containing trans fatty acids in comparison to a mixtur e of palmitic and oleic acids increase plasma cholesterol levels apparently by increasing endogenous synthesis of cholesterol.


Sumino, H., S. Ichikawa, et al. (2003). "Effects of hormone replacement therapy on circulating docosahexaenoic acid and eicosapentaenoic acid levels in postmenopausal women." Endocr J 50(1): 51-9.

            Hormone replacement therapy (HRT) has antiatherosclerotic effects of which the mechanism remains unclear. The ingestion of fish oil or other sources of n-3 polyunsaturated fatty acids has been included in comprehensive strategies to prevent atherosclerosis. Many epidemiologic studies have shown that the dietary intake of docosahexaenoic acid and eicosapentaenoic acid has antiatherosclerotic effects. We investigated the effect of HRT on plasma docosahexaenoic acid and eicosapentaenoic acid concentrations in postmenopausal women. Fifty-nine postmenopausal women, who received conjugated estrogens (0.625 mg/day) and medroxyprogesterone (2.5 mg/day) for 12 months, and 45 control postmenopausal women, who did not receive HRT, volunteered to participate in this study. Plasma docosahexaenoic acid and eicosapentaenoic acid concentrations were measured at baseline and at 6 and 12 months after the start of HRT. HRT significantly increased the plasma docosahexaenoic acid and eicosapentaenoic acid concentrations from 134 +/- 5 microg/ml and 69 +/- 4 microg/ml at baseline to 156 +/- 7 microg/ml and 85 +/- 7 microg/ml after 12 months (both p<0.01). However, the control group showed no significant change in their plasma docosahexaenoic acid and eicosapentaenoic acid levels during the study. HRT increased plasma docosahexaenoic acid and eicosapentaenoic acid levels in postmenopausal women. We propose that the increase in docosahexaenoic acid and eicosapentaenoic acid may be partially responsible for the beneficial mechanisms by which HRT induces an antiatherosclerotic effect in postmenopausal women.


Su, K. P., S. Y. Huang, et al. (2003). "Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial." Eur Neuropsychopharmacol 13(4): 267-71.

            Patients with depression have been extensively reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids (PUFAs), including significantly low eicosapentaenoic acid and docosahexaenoic acid in cell tissue contents (red blood cell membrane, plasma, etc.) and dietary intake. However, more evidence is needed to support its relation. In this study, we conducted an 8-week, double-blind, placebo-controlled trial, comparing omega-3 PUFAs (9.6 g/day) with placebo, on the top of the usual treatment, in 28 patients with major depressive disorder. Patients in the omega-3 PUFA group had a significantly decreased score on the 21-item Hamilton Rating Scale for Depression than those in the placebo group (P < 0.001). From the preliminary findings in this study, omega-3 PUFAs could improve the short-term course of illness and were well tolerated in patients with major depressive disorder.


Stulnig, T. M. (2003). "Immunomodulation by polyunsaturated fatty acids: mechanisms and effects." Int Arch Allergy Immunol 132(4): 310-21.

            Polyunsaturated fatty acids (PUFAs) modulate immune responses, thereby exerting beneficial effects in a variety of inflammatory disorders. PUFAs of the n-3 series that are found in marine fish oils are particularly effective. A variety of molecular mechanisms have been found to explain how PUFAs could interfere with immune cell function. PUFAs alter eicosanoid (prostaglandin, leukotriene) synthesis, orphan nuclear receptor activation (e.g. peroxisome proliferator-activated receptors, liver X receptors) and T lymphocyte signaling by changing the molecular composition of special signaling platforms called lipid rafts. This review discusses these mechanisms in detail with respect to their probable relevance in vivo. In addition, the effects of PUFAs on the immune system in general are summarized, as are clinical effects in rheumatoid arthritis, inflammatory bowel disease and sepsis.


Strokin, M., M. Sergeeva, et al. (2003). "Docosahexaenoic acid and arachidonic acid release in rat brain astrocytes is mediated by two separate isoforms of phospholipase A2 and is differently regulated by cyclic AMP and Ca2+." Br J Pharmacol 139(5): 1014-22.

            1. Docosahexaenoic acid (DHA) and arachidonic acid (AA), polyunsaturated fatty acids (PUFAs), are important for central nervous system function during development and in various pathological states. Astrocytes are involved in the biosynthesis of PUFAs in neuronal tissue. Here, we investigated the mechanism of DHA and AA release in cultured rat brain astrocytes. 2. Primary astrocytes were cultured under standard conditions and prelabeled with [(14)C]DHA or with [(3)H]AA. Adenosine 5'-triphosphate (ATP) (20 micro M applied for 15 min), the P2Y receptor agonist, stimulates release of both DHA (289% of control) and AA (266% of control) from astrocytes. DHA release stimulated by ATP is mediated by Ca(2+)-independent phospholipase A(2) (iPLA(2)), since it is blocked by the selective iPLA(2) inhibitor 4-bromoenol lactone (BEL, 5 micro M) and is not affected either by removal of Ca(2+) from extracellular medium or by suppression of intracellular Ca(2+) release through PLC inhibitor (U73122, 5 micro M). 3. AA release, on the other hand, which is stimulated by ATP, is attributed to Ca(2+)-dependent cytosolic PLA(2) (cPLA(2)). AA release is abolished by U73122 and, by removal of extracellular Ca(2+), is insensitive to BEL and can be selectively suppressed by methyl arachidonyl fluorophosphonate (3 micro M), a general inhibitor of intracellular PLA(2) s. 4. Western blot analysis confirms the presence in rat brain astrocytes of 85 kDa cPLA(2) and 40 kDa protein reactive to iPLA(2) antibodies. 5. The influence of cAMP on regulation of PUFA release was investigated. Release of DHA is strongly amplified by the adenylyl cyclase activator forskolin (10 micro M), and by the protein kinase A (PKA) activator dibutyryl-cAMP (1 mM). In contrast, release of AA is not affected by forskolin or dibutyryl-cAMP, but is almost completely blocked by 2,3-dideoxyadenosine (20 micro M) and inhibited by 34% by H89 (10 micro M), inhibitors of adenylyl cyclase and PKA, respectively. 6. Other neuromediators, such as bradykinin, glutamate and thrombin, stimulate release of DHA and AA, which is comparable to the release stimulated by ATP. 7. Different sensitivities of iPLA(2) and cPLA(2) to Ca(2+) and cAMP reveal new pathways for the regulation of fatty acid release and reflect the significance of astrocytes in control of DHA and AA metabolism under normal and pathological conditions in brain.


Stenzel, I., B. Hause, et al. (2003). "Jasmonate biosynthesis and the allene oxide cyclase family of Arabidopsis thaliana." Plant Mol Biol 51(6): 895-911.

            In biosynthesis of octadecanoids and jasmonate (JA), the naturally occurring enantiomer is established in a step catalysed by the gene cloned recently from tomato as a single-copy gene (Ziegler et al., 2000). Based on sequence homology, four full-length cDNAs were isolated from Arabidopsis thaliana ecotype Columbia coding for proteins with AOC activity. The expression of AOC genes was transiently and differentially up-regulated upon wounding both locally and systemically and was induced by JA treatment. In contrast, AOC protein appeared at constitutively high basal levels and was slightly increased by the treatments. Immunohistochemical analyses revealed abundant occurrence of AOC protein as well as of the preceding enzymes in octadecanoid biosynthesis, lipoxygenase (LOX) and allene oxide synthase (AOS), in fully developed tissues, but much less so in 7-day old leaf tissues. Metabolic profiling data of free and esterified polyunsaturated fatty acids and lipid peroxidation products including JA and octadecanoids in wild-type leaves and the jasmonate-deficient mutant OPDA reductase 3 (opr3) revealed preferential activity of the AOS branch within the LOX pathway. 13-LOX products occurred predominantly as esterified derivatives, and all 13-hydroperoxy derivatives were below the detection limits. There was a constitutive high level of free 12-oxo-phytodienoic acid (OPDA) in untreated wild-type and opr3 leaves, but an undetectable-expression of AOC. Upon wounding opr3 leaves exhibited only low expression of AOC, wounded wild-type leaves, however, accumulated JA and AOC mRNA. These and further data suggest regulation of JA biosynthesis by OPDA compartmentalization and a positive feedback by JA during leaf development.


Steinhart, H. and T. Rathjen (2003). "Dependence of tocopherol stability on different cooking procedures of food." Int J Vitam Nutr Res 73(2): 144-51.

            The influence of the kind of treatment during the preparation of hot meals (roasting, baking, stewing) on the stability of the tocopherols, which were added to the food through the margarines used, were examined in different food matrices. All preparation methods resulted in a loss of tocopherols. They could be divided into a group of only small loss of tocopherols (lower than 20%) and into a second group with nearly 70% loss of tocopherols (roasting of meat, steaming of peas). In the first group losses of tocopherols were directly associated with the fatty acid patterns of the used margarines, especially with the share of polyunsaturated fatty acids. On the other hand, during the roasting of meat nearly 70% of the tocopherols were destroyed by direct oxidation without a prohibitive effect on the lipid oxidation. The extreme high loss of tocopherols during the steaming of peas may be caused by the catalytic effect of the metal surface of the used pot. There were no losses of tocopherols observed when the experiments were repeated under identical conditions in an inert glass pot. Only tocopherol losses during baking may have a nutritional importance because of the great fat amount which are taken in with cookies.


Stein, J. (2003). "Visual motion sensitivity and reading." Neuropsychologia 41(13): 1785-93.

            Reading is more difficult than speaking because an arbitrary set of visual symbols must be rapidly identified, ordered and translated into the sounds they represent. Many poor readers have particular problems with the rapid visual processing required for these tasks because they have a mild impairment of the visual magnocellular system. This deficit has been demonstrated using neuropathological, evoked potential, functional magnetic resonance imaging and psychophysical techniques. The sensitivity of the M-system in both good and bad readers correlates with their orthographic abilities, suggesting that the M-system plays an important part in their development. This role is probably to mediate steady direction of visual attention and eye fixations on words. Thus many children with reading difficulties have unsteady eye control and this causes the letters they are trying to read to appear to move around, so that they cannot tell what order they are meant to be in. Therefore, boosting M-performance using yellow filters, or training eye fixation, can improve reading performance very significantly. Several genetic linkage studies have associated reading difficulties with the MHC control region on the short arm of chromosome 6. This system has recently been shown to help regulate the differentiation of M-cells. This association could also explain the high incidence of autoimmune conditions in poor readers. Other chromosomal sites are associated with the metabolism of polyunsaturated fatty acids (PUFAs) as found in fish oils, and this could explain why PUFA supplements can improve reading.


Stadtman, E. R. and R. L. Levine (2003). "Free radical-mediated oxidation of free amino acids and amino acid residues in proteins." Amino Acids 25(3-4): 207-18.

            We summarize here results of studies designed to elucidate basic mechanisms of reactive oxygen (ROS)-mediated oxidation of proteins and free amino acids. These studies have shown that oxidation of proteins can lead to hydroxylation of aromatic groups and aliphatic amino acid side chains, nitration of aromatic amino acid residues, nitrosylation of sulfhydryl groups, sulfoxidation of methionine residues, chlorination of aromatic groups and primary amino groups, and to conversion of some amino acid residues to carbonyl derivatives. Oxidation can lead also to cleavage of the polypeptide chain and to formation of cross-linked protein aggregates. Furthermore, functional groups of proteins can react with oxidation products of polyunsaturated fatty acids and with carbohydrate derivatives (glycation/glycoxidation) to produce inactive derivatives. Highly specific methods have been developed for the detection and assay of the various kinds of protein modifications. Because the generation of carbonyl derivatives occurs by many different mechanisms, the level of carbonyl groups in proteins is widely used as a marker of oxidative protein damage. The level of oxidized proteins increases with aging and in a number of age-related diseases. However, the accumulation of oxidized protein is a complex function of the rates of ROS formation, antioxidant levels, and the ability to proteolytically eliminate oxidized forms of proteins. Thus, the accumulation of oxidized proteins is also dependent upon genetic factors and individual life styles. It is noteworthy that surface-exposed methionine and cysteine residues of proteins are particularly sensitive to oxidation by almost all forms of ROS; however, unlike other kinds of oxidation the oxidation of these sulfur-containing amino acid residues is reversible. It is thus evident that the cyclic oxidation and reduction of the sulfur-containing amino acids may serve as an important antioxidant mechanism, and also that these reversible oxidations may provide an important mechanism for the regulation of some enzyme functions.


Speake, B. K., F. Decrock, et al. (2003). "Establishment of the fatty acid profile of the brain of the king penguin (Aptenodytes patagonicus) at hatch: effects of a yolk that is naturally rich in n-3 polyunsaturates." Physiol Biochem Zool 76(2): 187-95.

            Because the yolk lipids of the king penguin (Aptenodytes patagonicus) contain the highest concentrations of long-chain n-3 polyunsaturated fatty acids yet reported for an avian species, the consequences for the establishment of the brain's fatty acid profile in the embryo were investigated. To place the results in context, the fatty acid compositions of yolk lipid and brain phospholipid of the king penguin were compared with those from three other species of free-living birds. The proportions of docosahexaenoic acid (22:6n-3; DHA) in the total lipid of the initial yolks for the Canada goose (Branta canadensis), mallard (Anas platyrhynchos), moorhen (Gallinula chloropus), and king penguin were (% w/w of fatty acids) 1.0+/-0.1, 1.9+/-0.2, 3.3+/-0.1, and 5.9+/-0.2, respectively. The respective concentrations of DHA (% w/w of phospholipid fatty acids) in brains of the newly hatched chicks of these same species were 18.5+/-0.2, 19.6+/-0.7, 16.9+/-0.4, and 17.6+/-0.1. Thus, the natural interspecies diversity in yolk fatty acid profiles does not necessarily produce major differences in the DHA content of the developing brain. Only about 1% of the amount of DHA initially present in the yolk was recovered in the brain of the penguin at hatch. There was no preferential uptake of DHA from the yolk during development of the king penguin.


Speake, B. K., E. A. Deans, et al. (2003). "Differential incorporation of docosahexaenoic and arachidonic acids by the yolk sac membrane of the avian embryo." Comp Biochem Physiol B Biochem Mol Biol 136(2): 357-67.

            During avian development, lipoproteins derived from yolk lipid are assembled in the yolk sac membrane (YSM) for secretion into the embryonic circulation. To investigate how yolk polyunsaturated fatty acids, essential for the development of certain tissues, are distributed among the lipid classes of the lipoproteins, pieces of YSM were incubated in vitro with [14C]arachidonic and [14C]docosahexaenoic acids (DHA). There was a marked difference in the partitioning of these two precursors among the lipid classes of the tissue. Of the radioactivity incorporated into total lipid from [14C]-arachidonic acid during 1 h of incubation, 67.3% was esterified as phospholipid and 29.5% as triacylglycerol. In contrast, only 14.6% of the label incorporated from [14C]-DHA was esterified as phospholipid, whereas 73.2% was recovered in triacylglycerol. This pattern of differential partitioning was observed at all time points and across a 20-fold range of fatty acid concentrations. There was no evidence for conversion of the radioactive arachidonic and DHAs to other fatty acids prior to incorporation into tissue lipids. It is suggested that the selective incorporation of yolk-derived DHA into the triacylglycerol of secreted lipoproteins represents part of a mechanism for directing this polyunsaturate to particular embryonic tissues.


Soriguer, F., F. Moreno, et al. (2003). "Monounsaturated n-9 fatty acids and adipocyte lipolysis in rats." Br J Nutr 90(6): 1015-22.

            To investigate the role of the monounsaturated n-9 fatty acids (MUFA) in the lipolytic activity of adipocytes, a study was carried out in which an increase in MUFA was produced in the tissues by two different methods; by the dietary enrichment of oleic acid or by producing an essential fatty acid deficiency syndrome. For this, forty-five male Sprague-Dawley rats were fed with a normal-energy diet and were subdivided into three groups. The diets varied in the type of dietary fat; palmitic acid, olive oil, or soyabean oil+palmitic acid. At the end of the study measurements were taken of weight, plasma leptin, tissue concentration of fatty acids, fat-cell size in the epididymal and the omental adipose tissues, adipocyte lipolytic activity of both tissues after stimulation with adrenaline, and the capacity of insulin to inhibit lipolysis. The baseline and adrenaline-stimulated lipolytic activity were greater and the anti-lipolytic capacity of insulin lower in the animals undergoing an increase in MUFA in the tissues (palmitic-acid and olive-oil diets). The area under the curve of glycerol, used as an indicator of lipolytic activity, was positively correlated with the concentration of MUFA and negatively with polyunsaturated fatty acids in the adipose tissues. It is concluded that an increase in tissue MUFA, however obtained, induces an increase in lipolytic activity.


Sneddon, A. A., H. C. Wu, et al. (2003). "Regulation of selenoprotein GPx4 expression and activity in human endothelial cells by fatty acids, cytokines and antioxidants." Atherosclerosis 171(1): 57-65.

            Phospholipid hydroperoxide glutathione peroxidase (GPx4) is the only antioxidant enzyme known to directly reduce phospholipid hydroperoxides within membranes and lipoproteins, acting in conjunction with alpha-tocopherol to inhibit lipid peroxidation. Peroxidation of lipids has been implicated in a number of pathophysiological processes, including inflammation and atherogenesis. We investigated the relative positive and negative effects of specific polyunsaturated fatty acids (PUFAs) and inflammatory cytokines on the activity and gene expression of the selenium-dependant redox enzyme GPx4. In human umbilical vein endothelial cells (HUVEC), GPx4 mRNA levels and activity were increased optimally by 114 nM selenium (as sodium selenite). Docosahexaenoic acid (DHA) and conjugated linoleic acid (CLA) further increased mRNA levels whereas arachidonic acid (ARA) had no effect; enzyme activity was decreased by DHA, was unaffected by CLA or was increased by ARA. GPx4 protein levels increased with selenium, ARA and DHA addition but not with CLA. Interleukin-1beta (IL-1beta) increased GPx4 mRNA, protein and activity whereas TNFalpha at 1 ng/ml increased activity while at 3 ng/ml it reduced activity and mRNA. Conversely, alpha-tocopherol reduced mRNA levels without affecting activity. These results indicate that lipids, cytokines and antioxidants modulate GPx4 in a complex manner that in the presence of adequate selenium, may favour protection against potentially proatherogenic processes.


Smuts, C. M., M. Huang, et al. (2003). "A randomized trial of docosahexaenoic acid supplementation during the third trimester of pregnancy." Obstet Gynecol 101(3): 469-79.

            OBJECTIVE: To hypothesize that higher intake of docosahexaenoic acid, an n-3 long chain polyunsaturated fatty acid, would increase duration of gestation and birth weight in US women. METHODS: This was a randomized, double-blind, controlled, clinical trial. Subjects were enrolled in an ambulatory clinic where they received prenatal care. This was a population-based sample. Most subjects received government assistance for medical care and most were black (73%). Subjects were enrolled between the 24th and 28th week of pregnancy and consumed docosahexaenoic acid (33 or 133 mg) from eggs until parturition. Gestational age and birth weight were the main study outcomes. Infant length and head circumference, preterm birth, and low birth weight were secondary outcomes. RESULTS: Eighty-three percent of subjects completed the study (291 of 350 enrolled). No subject was discontinued for an adverse event. After controlling for important predefined risk factors and confounding variables, gestation increased by 6.0 +/- 2.3 days (P =.009) in the higher docosahexaenoic acid group. Birth weight, length, and head circumference increased, but did not reach statistical significance (P =.06-.18), although the increases could be clinically important indications of enhanced intrauterine growth. No safety concerns were raised by the study. CONCLUSION: Duration of gestation increased significantly when docosahexaenoic acid intake was increased during the last trimester of pregnancy. The increase in gestation was similar to that reported for interventions with much larger amounts of n-3 long chain polyunsaturated fatty acids.


Smith, M. A., H. Moon, et al. (2003). "Heterologous expression of a fatty acid hydroxylase gene in developing seeds of Arabidopsis thaliana." Planta 217(3): 507-16.

            Expression of a cDNA encoding the castor bean ( Ricinus communis L.) oleate Delta12-hydroxylase in the developing seeds of Arabidopsis thaliana (L.) Heynh. results in the synthesis of four novel hydroxy fatty acids. These have been previously identified as ricinoleic acid (12-hydroxy-octadec- cis-9-enoic acid: 18:1-OH), densipolic acid (12-hydroxy-octadec- cis-9,15-enoic acid: 18:2-OH), lesquerolic acid (14-hydroxy-eicos- cis-11-enoic acid: 20:1-OH) and auricolic acid (14-hydroxy-eicos- cis-11,17-enoic acid: 20:2-OH). Using mutant lines of Arabidopsis that lack the activity of the FAE1 condensing enzyme or FAD3 ER Delta-15-desaturase, we have shown that these enzymes are required for the synthesis of C20 hydroxy fatty acids and polyunsaturated hydroxy fatty acids, respectively. Analysis of the seed fatty acid composition of transformed plants demonstrated a dramatic increase in oleic acid (18:1) levels and a decrease in linoleic acid (18:2) content correlating to the levels of hydroxy fatty acid present in the seed. Plants in which FAD2 (ER Delta12-desaturase) activity was absent showed a decrease in 18:1 content and a slight increase in 18:2 levels corresponding to hydroxy fatty acid content. Expression of the castor hydroxylase protein in yeast indicates that this enzyme has a low level of fatty acid Delta12-desaturase activity. Lipase catalysed 1,3-specific lipolysis of triacylglycerol from transformed plants demonstrated that ricinoleic acid is not excluded from the sn-2 position of triacylglycerol, but is the only hydroxy fatty acid present at this position.


Smit, E. N., I. A. Martini, et al. (2003). "Fatty acids in formulae for term infants: compliance of present recommendations with the actual human milk fatty acid composition of geographically different populations." Acta Paediatr 92(7): 790-6.

            AIM: Recommendations for formula fatty acids (FA) are largely based on the mature human milk FA composition. This study aimed to investigate whether current recommendations for formula FA for term infants comply with the actual breast-milk FA composition of geographically distinct populations and to provide more realistic grounds for future recommendations. METHODS: 455 mature breast-milk samples were collected in different countries over 25 y. Recommendations of different organizations were projected on their FA data. FA interrelationships were calculated with Spearman's rank tests. FA compositions of 30 formulae were compared with those of breast milk. RESULTS: Many samples from non-Western communities did not meet the recommendations for formula 12:0, 14:0 and 18:2omega6, since these are mainly based on breast milk of mothers living in Western countries. Recommendations for 18:3omega3, 18:2omega6/18:3omega3, 20:4omega6 and 22:6omega3 were not met by many milk samples, which may point to the poorly developed recommendations for long-chain polyunsaturated FA. Most of the investigated breast-milk FA (12:0, 14:0, 16:0, 18:0, 18:3omega3, 22:6omega3, 18:2omega6, 20:4omega6, 18:1omega9) were either positively or negatively interrelated. Many formulae had FA compositions that were not consistent with the physiological interrelationships of FA in breast milk. CONCLUSION: Future recommendations, if based on human milk, should derive from its FA balance, as indicated by the FA interrelationships. A "humanized" formula FA composition would in this sense be any composition that cannot be distinguished from that of breast milk by techniques such as principal component analysis.


Skrzypczak-Jankun, E., K. Zhou, et al. (2003). "Inhibition of lipoxygenase by (-)-epigallocatechin gallate: X-ray analysis at 2.1 A reveals degradation of EGCG and shows soybean LOX-3 complex with EGC instead." Int J Mol Med 12(4): 415-20.

            Lipoxygenases (LOXs) are non-heme iron containing enzymes ubiquitous in nature and participating in the metabolism of the polyunsaturated fatty acids (PUFA). They are capable of combining their dioxygenase activity with its co-oxidative activity manifesting itself in biotransformation reactions catalyzed by LOXs for other than PUFA small molecules. LOXs involvement in inflammatory diseases and cancer have been well documented. Catechins are the natural flavonoids of known inhibitory activity toward dioxygenases with a potential to be utilized in disease prevention and treatment. This work presents results obtained from an X-ray analysis of (-)-epigallocatechin gallate (EGCG) interacting with soybean lipoxygenase-3. The 3D structure of the resulting complex reveals the inhibitor depicting (-)-epigallo-catechin that lacks galloyl moiety. The A-ring is near the iron co-factor, attached by the hydrogen bond to the C-terminus of the enzyme, and the B-ring hydroxyl groups participate in the hydrogen bonds and the van der Waals interactions formed by the surrounding amino acids and water molecules.


Skottova, N., R. Vecera, et al. (2003). "Effects of polyphenolic fraction of silymarin on lipoprotein profile in rats fed cholesterol-rich diets." Pharmacol Res 47(1): 17-26.

            To study the influence of polymerised polyphenolics (PP), a fraction of silymarin (SM), on lipids and oxidant status, rats were fed high-cholesterol (1%), high-fat (10%) diets containing either lard fat (LFD) rich in saturated/monounsaturated fatty acids, or currant oil (COD) rich in polyunsaturated fatty acids. PP and SM were administered as dietary supplements (0.1-0.5-1.0%) for 3 weeks. PP (1%) decreased cholesterol (C) in VLDL (from 0.72+/-0.08 mmol l(-1) in LFD control to 0.35+/-0.07 mmol l(-1), P<0.01, and from 0.33+/-0.05 mmol l(-1) in COD control to 0.09+/-0.02 mmol l(-1), P<0.001), and increased HDL-C/VLDL-C ratio, however, without effect on the total plasma C and LDL-C. Liver C content (LFD 19.32+/-1.50 micromol g(-1), COD 18.64+/-2.13 micromol g(-1), N.S.) decreased after PP (1%) to 12.24+/-0.76 micromol g(-1), P<0.01, and 8.78+/-0.95 micromol g(-1), P<0.001, respectively. Triacylglycerols (TAG) in plasma and VLDL decreased after PP in the LFD group only, which displayed higher TAG levels than the COD group. Likewise, LFD caused a higher liver TAG content than did COD (31.16+/-3.00 micromol g(-1) versus 17.31+/-1.48 micromol g(-1), P<0.01), and PP (1%) decreased liver TAG only in rats fed LFD (19.55+/-2.43 micromol g(-1), P<0.02). Blood glutathione (GSH) increased after PP (1%) in the LFD group from 0.97+/-0.11 to 1.54+/-0.19 mmol l(-1) (P<0.05) and in the COD group from 0.58+/-0.15 to 1.23+/-0.10 mmol l(-1) (P<0.01), while liver GSH and plasma TBARS did not change. On principle, effects of PP were dose-dependent and parallel to SM. These results suggest that the polyphenolic fraction of SM positively modifies lipoprotein profile, counteracts the development of fatty liver and ameliorates an antioxidant status in circulation.


Skosnik, P. D. and J. K. Yao (2003). "From membrane phospholipid defects to altered neurotransmission: is arachidonic acid a nexus in the pathophysiology of schizophrenia?" Prostaglandins Leukot Essent Fatty Acids 69(6): 367-84.

            Schizophrenia (SZ) is a devastating neuropsychiatric disorder affecting 1% of the general population, and is characterized by symptoms such as delusions, hallucinations, and blunted affect. While many ideas regarding SZ pathogenesis have been put forth, the majority of research has focused on neurotransmitter function, particularly in relation to altered dopamine activity. However, treatments based on this paradigm have met with only modest success, and current medications fail to alleviate symptoms in 30-60% of patients. An alternative idea postulated a quarter of a century ago by Feldberg (Psychol. Med. 6 (1976) 359) and Horrobin (Lancet 1 (1977) 936) involves the theory that SZ is associated in part with phospholipid/fatty acid abnormalities. Since then, it has been repeatedly shown that in both central and peripheral tissue, SZ patients demonstrate increased phospholipid breakdown and decreased levels of various polyunsaturated fatty acids (PUFAs), particularly arachidonic acid (AA). Given the diverse physiological function of membrane phospholipids and PUFAs, an elucidation of their role in SZ pathophysiology may provide novel strategies in the treatment of this disorder. The purpose of this review is to summarize the relevant data on membrane phospholipid/PUFA defects in SZ, the physiological consequence of altered AA signaling, and how they relate to the neurobiological manifestations of SZ and therapeutic outcome.


Skopinska-Rozewska, E., J. Chorostowska-Wynimko, et al. (2003). "Inhibitory effect of Greenland shark liver oil combined with squalen and arctic birch ashes on angiogenesis and L-1 sarcoma growth in Balb/c mice." Pol J Vet Sci 6(3 Suppl): 54-6.

            Sharks have been claimed to be resistant to cancer and oil from their livers have been used in Scandinavian folk medicine as anti-tumor drug. Shark liver oil contains 40% or more of squalene. Fish liver oil is also rich in squalene and polyunsaturated n-3 fatty acids. The aim of this work was to determine the anti-angiogenic and anti-tumor effects of these substances, together with another Scandinavian traditional remedy--arctic birch ashes--in Balb/c mice after transplantation of syngeneic L-1 sarcoma. All substances tested, alone or in combinations, significantly diminished cutaneous angiogenesis induced by tumor cells, and tumor growth.


Skerrett, P. J. and C. H. Hennekens (2003). "Consumption of fish and fish oils and decreased risk of stroke." Prev Cardiol 6(1): 38-41.

            Consumption of fish and fish oils was first associated with decreased risk of cardiovascular disease almost 50 years ago. Since then, a number of epidemiologic studies have evaluated whether their consumption is specifically associated with stroke. Ecologic/cross-sectional and case-control studies have generally shown an inverse association between consumption of fish and fish oils and stroke risk. Results from five prospective studies have been less consistent, with one showing no association, one showing a possible inverse association, and three demonstrating a significant inverse association. In the latest and largest of these, the Nurses Health Study, the relative risk of total stroke was lower, although not significantly so, among women who regularly ate fish than among those who did not. A significant decrease in the risk of thrombotic stroke (relative risk, 0.49; 95% confidence interval, 0.26-0.93) was observed among women who ate fish at least two times per week compared with women who ate fish less than once per month, after adjustment for age, smoking, and other cardiovascular risk factors; a nonsignificant decrease was observed among women in the highest quintile of long-chain omega-3 polyunsaturated fatty acid intake. No association was observed between consumption of fish or fish oil and hemorrhagic stroke. These data support the hypothesis that consumption of fish several times per week reduces the risk of thrombotic stroke but does not increase the risk of hemorrhagic stroke.


Siscovick, D. S., R. N. Lemaitre, et al. (2003). "The fish story: a diet-heart hypothesis with clinical implications: n-3 polyunsaturated fatty acids, myocardial vulnerability, and sudden death." Circulation 107(21): 2632-4.


Sirri, F., N. Tallarico, et al. (2003). "Fatty acid composition and productive traits of broiler fed diets containing conjugated linoleic acid." Poult Sci 82(8): 1356-61.

            An experiment was carried out to evaluate the transfer of dietary CLA to broiler chicken tissues (breast, drumstick meat, skin, and abdominal fat) and its effect on productive traits and on carcass yields of birds. Cobb 500 females (n=360), divided into three groups, received from 22 d to slaughtering age (47 d) a grower diet supplemented with 2% conjugated linoleic acid (CLA) source containing 60% CLA methyl esters (CLA2) or 4% CLA source (CLA4). The control group had no supplementation. The addition of CLA source to chicken diet decreased the content of monounsaturated fatty acid (MUFA) (oleic and palmitoleic acids) in breast and drumstick meat. The deposition of CLA in muscles significantly increased as the dietary CLA increased, whereas only little amounts of CLA were detected in the control group. Arachidonic acid (ARA) content was significantly depressed and linearly related to the addition of CLA to the chicken diet. Other non-CLA polyunsaturated fatty acids (PUFA) were little affected by the dietary CLA supplementation. Saturated fatty acids (myristic and stearic acids) significantly increased about 30% in abdominal fat pad of both treated groups enhancing the firmness of abdominal fat. Productive performances--as well as carcass yields--were similar across dietary treatment of birds.


Sirois, I., A. M. Cheung, et al. (2003). "Biomechanical bone strength and bone mass in young male and female rats fed a fish oil diet." Prostaglandins Leukot Essent Fatty Acids 68(6): 415-21.

            The study objective was to determine if male and female rats fed a diet rich in fish oil had femurs and vertebrae that were stronger and more resistant to fracture than rats not fed omega-3 long chain polyunsaturated fatty acids. Weanling rats were randomized to a control or a fish oil diet for 5 weeks. Feeding fish oil to males had no effect on biomechanical strength properties of femurs and vertebrae as measured by three point bending and compression, respectively. In contrast, females fed fish oil had reduced length growth and a lower vertebral peak load. These effects may have been partly mediated by a lower food intake but were not associated with differences in serum IGF-I, estradiol or urinary calcium. The effect of consuming a fish oil diet into later adulthood should be investigated to determine if femur strength is also affected among females.


Silveira Rodriguez, M. B., S. Monereo Megias, et al. (2003). "[Functional nutrition and optimal nutrition. Near or far?]." Rev Esp Salud Publica 77(3): 317-31.

            The concept of functional food, about which scientific agreement is still lacking, springs from the field of Optimum Nutrition, aimed at modifying genetic and physiological aspects of human life and at the prevention and treatment of a growing number of diseases, far beyond merely covering nutritional requirements. From the European Union perspective, functional foods can be natural as well as industrially processed foods. The leading functional foods regarding which the soundest scientific evidence exists are probiotics, live microbial food ingredients represented mainly by fermented dairy products. Prebiotics, such as inulin-type fructans, are the trophic substrate of probiotics and potential intestinal microflora selectors. The combination of prebiotics and probiotics is termed synbiotic. Innumerable substances are known to have functional effects: soluble and insoluble fiber, phytosterols, phytoestrogens, monounsaturated and polyunsaturated fatty acids, phenol derivatives, vitamins and other phytochemicals. Functional foods exert their actions on different systems, especially the gastrointestinal, cardiovascular and immunological ones, acting too as enhancers of development and differentiation and positively modulating nutrient metabolism, gene expression, oxidative stress and the psychic sphere. The establishment of Health Claims must be firmly based upon scientific knowledge and legal regulation. Efficient biomarkers related to biological response must be found. Furthermore, it is essential to analyze possible diet or drug interactions as well as it is indispensable to conduct valid studies on humans. The prime objective must be the diet as a whole. Thus, the future challenge of a functional diet emerges.


Sijben, J. W., K. C. Klasing, et al. (2003). "Early in vivo cytokine genes expression in chickens after challenge with Salmonella typhimurium lipopolysaccharide and modulation by dietary n--3 polyunsaturated fatty acids." Dev Comp Immunol 27(6-7): 611-9.

            We studied the effects of Salmonella typhimurium lipopolysaccharide (LPS) on in vivo cytokine mRNA levels in chickens, and investigated whether these levels could be altered by different nutrients. Two hundred and forty chicks were assigned in a 2 x 4 factorial design of treatments. Factors were intravenous injection with S. typhimurium LPS, or saline (control), and four dietary fat sources: corn oil (CO), linseed oil (LO), menhaden oil and beef tallow (BT). Two hours after injection birds were killed and their spleens removed for RNA extraction. Quantitative real-time RT-PCR assays for mRNA of chicken IFN-gamma, IL-6, IL-8, IL-15, IL-18 and 28S rRNA were used to obtain the in vivo splenic cytokine profiles. Expression levels of IL-6, IL-8, IL-18 and IFN-gamma mRNA increased, but IL-15 mRNA decreased 2h after challenge with LPS compared with saline controls. In saline-injected control chickens, the dietary oil source did not affect the splenic mRNA level of any cytokine. In LPS challenged chickens IFN-gamma mRNA was significantly higher in the chickens fed the fish oil enriched diet compared with the LO, CO and BT enriched diets. The present data imply that avian IL-15 has, at least partially, a different function compared to its mammalian counterpart, and in addition, chicken innate immune responses might be affected differently by n-3 PUFA compared to mammals.


Sidhu, K. S. (2003). "Health benefits and potential risks related to consumption of fish or fish oil." Regul Toxicol Pharmacol 38(3): 336-44.

            The nutritional benefits of fish consumption relate to the utilization of proteins of high biological value, as well as certain minerals and vitamins that fish provide. Fish or fish oil contains omega-3 polyunsaturated fatty acids (PUFAs) that appear to play several useful roles for human health. Conversely, some carcinogenic contaminants are also stored in the adipose tissue of fish. The objective of this paper is to evaluate the potential health benefits and risks related to the consumption of fish or fish oil. Health benefits related to the consumption of fish or omega-3 PUFAs were obtained by an extensive literature search. Potential health risks related to carcinogenic contaminants (e.g., dioxin, PCB, etc.) in fish were estimated using the U.S. EPA-approved cancer risk assessment guidelines. Potential health risk estimates were evaluated by comparing them with the acceptable excess risk level of 10(-6)-10(-4). Scientific data indicate that the consumption of fish or fish oil containing omega-3 PUFAs reduces the risk of coronary heart disease, decreases mild hypertension, and prevents certain cardiac arrhythmias and sudden death. Risk estimates in humans for carcinogenic environmental contaminants in fish ranged from an excess risk level of 3x10(-6)-9x10(-4). These risk estimates appeared to meet the acceptable excess risk level criteria. Therefore, consumption of fish in accordance with the State of Michigan Fish Advisory Guidelines is safe and should be encouraged. The top 11 fish species [e.g., sardines, mackerel, herring (Atlantic and Pacific), lake trout, salmon (Chinook, Atlantic, and Sockeye), anchovy (European), sablefish, and bluefish] provide an adequate amount of omega-3 PUFAs (2.7-7.5g/meal) and appear to meet the nutritional recommendation of the American Heart Association.


Sidell, K. R., K. S. Montine, et al. (2003). "Mercapturate metabolism of 4-hydroxy-2-nonenal in rat and human cerebrum." J Neuropathol Exp Neurol 62(2): 146-53.

            4-Hydroxy-2-nonenal (HNE), a potent toxin formed in the brain from oxidation of polyunsaturated fatty acids, is increased in Alzheimer disease (AD), where it is a proposed effector of amyloid beta peptide-mediated neurotoxicity. Detoxification of HNE via the mercapturic acid pathway (MAP) is the primary means by which other organs, such as liver, limit its toxic effects. Here we examined the distribution and activity of MAP detoxification for HNE in cerebrum. Our results showed that rat cerebral cortex and especially synaptosomes were less well equipped to detoxify HNE via the MAP than liver. Glutathione transferases (GSTs) catalyze the committed step in the MAP; GST-mu and GST-pi, but not OST-alpha, were detected in neurons and astrocytes in cerebrum from AD patients and controls. MAP activity in frontal cortex of AD patients was modestly but significantly increased compared to controls. These data suggest that lipid peroxidation may present a greater toxic burden to cerebrum than to other organs, and that a component of response to injury in late stage AD is a slight increase in MAP activity.


Shnizer, S., T. Kagan, et al. (2003). "Modifications and oxidation of lipids and proteins in human serum detected by thermochemiluminescence." Luminescence 18(2): 90-6.

            Detection of electronically excited species (EES) in body fluids may constitute an important diagnostic tool in various pathologies. Examples of such products are triplet excited carbonyls (TEC), which can be a source for photon emission in the 400-550 nm range. The aim of the present study was to determine the actual contribution of lipid and protein components (protein carbonyls) to photon emission generated by thermochemiluminescence (TCL) during the heating of biological fluids. In this study, a new TCL Photometer device, designed by Lumitest Ltd, Israel, was used. Samples were heated to a constant temperature of 80 +/- 0.5 degrees C for 280 s and photon emission was measured at several time points. In order to compare the results of TCL measurements to conventional methods of detecting lipid and protein oxidation, each examined sample was also heated in a waterbath at 80 degrees C for 10-280 s. Lipid and protein oxidation were subsequently measured using conventional methods. The TCL of four polyunsaturated fatty acids (PUFA) with three to six double bonds was measured. The elevation of the PUFA TCL amplitude correlated with the increase in the number of double bonds of PUFA. A correlation between the increase in TCL intensity and protein carbonyl generation in bovine serum albumin (BSA) was also observed. In the venous blood serum, our study showed that an increase of TCL intensity during heating reflected the cleavage of TEC of lipid origin. Our study suggests that biological molecules such as proteins, lipids and other molecules, which may become unstable during heating, are capable of generating EES. We demonstrated that a TCL curve can be used as a kinetic model for measuring oxidative processes, which reflects modifications of different molecules involved in the oxidative stress phenomena.


Shimizu, T., M. Suzuki, et al. (2003). "Effects of n-3 polyunsaturated fatty acids on indomethacin-induced changes in eicosanoid production and blood flow in the gastric mucosa of rats." Prostaglandins Leukot Essent Fatty Acids 69(1): 33-7.

            We investigated the effects of n-3 polyunsaturated fatty acids (PUFAs) on non-steroidal anti-inflammatory drug (NSAID)-induced changes in microcirculation and eicosanoid production in the gastrointestinal mucosa. We measured gastric mucosal blood flow using laser Doppler flowmetry, assessed the fatty acid composition in the mucosal phospholipids, and quantified the production of prostaglandin E2 (PGE2), leukotriene B4, and leukotriene C4 (LTB4 and C4) from the mucosa with the stimulation of calcium ionophore 20 min after an injection of indomethacin or vehicle in rats fed a diet containing different compositions of alpha-linolenic acid. Four weeks after the initiation of the test diet the arachidonic acid level in gastric mucosal phospholipids was significantly lower in the perilla group than in the other three groups. Conversely, alpha-linolenic acid and eicosapentaenoic acid (EPA) were significantly higher in the perilla group than in the other three groups. The percent of gastric mucosal blood flow in the three groups administered indomethacin were significantly lower than that in the control group injected with vehicle alone. The percent of gastric mucosal blood flow in the perilla group was significantly higher than that in the corn group. LTB4 and LTC4 production from the gastric mucosa in the soybean and corn groups were significantly higher than those in the control group, and the LTC4 production in the perilla group was significantly lower than that in the corn group. There were no significant differences in PGE2 production among the four groups. Our results suggest that alpha-linolenic acid affectively suppressed the indomethacin-induced decreases in gastric mucosal blood flow by increasing EPA and decreasing the levels of arachidonic acid and LTC4 in the gastric mucosa.


Shimizu, T., T. Fujii, et al. (2003). "Effects of highly purified eicosapentaenoic acid on erythrocyte fatty acid composition and leukocyte and colonic mucosa leukotriene B4 production in children with ulcerative colitis." J Pediatr Gastroenterol Nutr 37(5): 581-5.

            BACKGROUND: n-3 Polyunsaturated fatty acids (PUFAs) have been suggested as a treatment for ulcerative colitis (UC). However, the efficacy of n-3 PUFAs against UC has not been examined in children. Therefore, the authors investigated the effects of eicosapentaenoic acid (EPA) on fatty acid composition and leukotriene (LT) production in children with UC. METHODS: For 2 months the authors administered highly purified EPA ethyl ester (EPA-E) (1.8 g/d) to children with UC in remission. Colonic mucosal histology, fatty acid composition of erythrocyte membrane phospholipids, and LTB4 production by leukocytes and colonic mucosa were measured before and 2 months after the initiation of EPA-E treatment. RESULTS: No patients relapsed during the study period, and no significant differences were detected in laboratory findings obtained before and 2 months after the initiation of EPA-E ingestion. There were no significant differences in mucosal histologic scores before and 2 months after EPA-E treatment. The EPA levels in erythrocyte membranes 2 months after the initiation of EPA-E treatment were significantly higher than before treatment, but the other fatty acids showed no significant changes. LTB4 production by leukocytes and rectal mucosa after 2 months of EPA-E treatment was significantly lower than before treatment. CONCLUSION: EPA-E treatment increased the levels of EPA in erythrocytes and decreased LTB4 levels produced by leukocytes and colonic mucosa. To assess the concomitant clinical changes, we should examine the long-term effects of EPA-E ingestion on the maintenance of remission in children with UC.


Sharon, R., I. Bar-Joseph, et al. (2003). "The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson's disease." Neuron 37(4): 583-95.

            Accumulation of misfolded proteins as insoluble aggregates occurs in several neurodegenerative diseases. In Parkinson's disease (PD) and dementia with Lewy bodies (DLB), alpha-synuclein (alpha S) accumulates in insoluble inclusions. To identify soluble alpha S oligomers that precede insoluble aggregates, we probed the cytosols of mesencephalic neuronal (MES) cells, normal and alpha S-transgenic mouse brains, and normal, PD, and DLB human brains. All contained highly soluble oligomers of alpha S whose detection was enhanced by delipidation. Exposure of living MES neurons to polyunsaturated fatty acids (PUFAs) increased alpha S oligomer levels, whereas saturated FAs decreased them. PUFAs directly promoted oligomerization of recombinant alphaS. Transgenic mice accumulated soluble oligomers with age. PD and DLB brains had elevated amounts of the soluble, lipid-dependent oligomers. We conclude that alpha S interacts with PUFAs in vivo to promote the formation of highly soluble oligomers that precede the insoluble alpha S aggregates associated with neurodegeneration.


Sharon, R., I. Bar-Joseph, et al. (2003). "Altered fatty acid composition of dopaminergic neurons expressing alpha-synuclein and human brains with alpha-synucleinopathies." J Biol Chem 278(50): 49874-81.

            Alpha-synuclein (alphaS) is an abundant neuronal protein that accumulates in insoluble inclusions in Parkinson's disease (PD) and the related disorder, dementia with Lewy bodies (DLB). A central question about the role of alphaS in the pathogenesis of PD and DLB concerns how this normally soluble protein assembles into insoluble aggregates associated with neuronal dysfunction. We recently detected highly soluble oligomers of alphaS in normal brain supernatants and observed their augmentation in PD and DLB brains. Further, we found that polyunsaturated fatty acids (PUFAs) enhanced alphaS oligomerization in intact mesencephalic neuronal cells. We now report the presence of elevated PUFA levels in PD and DLB brain soluble fractions. Higher PUFA levels were also detected in the supernatants and high-speed membrane fractions of neuronal cells over-expressing wild-type or PD-causing mutant alphaS. This increased PUFA content in the membrane fraction was accompanied by increased membrane fluidity in the alphaS overexpressing neurons. In accord, membrane fluidity and the levels of certain PUFAs were decreased in the brains of mice genetically deleted of alphaS. Together with our earlier observations, these results suggest that alphaS-PUFA interactions help regulate neuronal PUFA levels as well as the oligomerization state of alphaS, both normally and in human synucleinopathies.


Shapiro, H. (2003). "Could n-3 polyunsaturated fatty acids reduce pathological pain by direct actions on the nervous system?" Prostaglandins Leukot Essent Fatty Acids 68(3): 219-24.

            The intake of n-3 polyunsaturated fatty acids (PUFAs) in many industrialized countries is relatively low and its increased consumption has protective and modifying effects on such diverse conditions as atherosclerosis, ventricular arrhythmias, multiple sclerosis, major depression and inflammatory and autoimmune diseases. In addition, n-3 PUFAs have been shown to alleviate pain in patients with rheumatoid arthritis, inflammatory bowel disease and in a number of other painful conditions. This has been attributed to the inhibition of pro-inflammatory eicosanoid and cytokine production by peripheral tissues. n-3 PUFAs have also been shown to inhibit eicosanoid production in glial cells, block voltage-gated sodium channels (VGSCs), inhibit neuronal protein kinases and modulate gene expression. They also appear to have mood-stabilizing and sympatholytic effects. The present article explores the possibility that, based on what is known about their neural and non-neural effects, n-3 PUFAs directly attenuate the neuronal and glial processes that underlie neuropathic and inflammatory pain.


Sekiya, M., N. Yahagi, et al. (2003). "Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression." Hepatology 38(6): 1529-39.

            Leptin-deficient ob/ob mice show many characteristics of obesity, including excess peripheral adiposity as well as severe hepatic steatosis, at least in part, due to increased hepatic lipogenesis. Polyunsaturated fatty acids (PUFAs) are not only ligands for peroxisome proliferator-activated receptor (PPAR) alpha but are also negative regulators of hepatic lipogenesis, which is thought to be mediated by the repression of sterol regulatory element-binding protein (SREBP)-1. We have previously shown that the disruption of SREBP-1 in ob/ob mice decreased their liver triglyceride storage. To examine whether PUFAs could reduce hepatic triglyceride deposition, we challenged ob/ob mice with dietary PUFA. It is demonstrated that PUFA markedly decreased the mature form of SREBP-1 protein and thereby reduced the expression of lipogenic genes such as fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1) in the livers of ob/ob mice. Consequently, the liver triglyceride content and plasma alanine aminotransferase (ALT) levels were decreased. Furthermore, both hyperglycemia and hyperinsulinemia in ob/ob mice were improved by PUFA administration, similar to the effect of PPARalpha activators. In conclusion, PUFAs ameliorate obesity-associated symptoms, such as hepatic steatosis and insulin resistance, presumably through both down-regulation of SREBP-1 and activation of PPARalpha.


Scollan, N. D., M. Enser, et al. (2003). "Effects of including a ruminally protected lipid supplement in the diet on the fatty acid composition of beef muscle." Br J Nutr 90(3): 709-16.

            Enhancing the polyunsaturated fatty acid (PUFA) and decreasing the saturated fatty acid content of beef is an important target in terms of improving the nutritional value of this food for the consumer. The present study examined the effects of feeding a ruminally protected lipid supplement (PLS) rich in PUFA on the fatty acid composition of longissimus thoracis muscle and associated subcutaneous adipose tissue. Animals were fed ad libitum on grass silage plus one of three concentrate treatments in which the lipid source was either Megalac (rich in palmitic acid; 16 : 0) or PLS (soybean, linseed and sunflower-seed oils resulting in an 18 : 2n-6:18 : 3n-3 value of 2.4:1). Treatment 1 contained 100 g Megalac/kg (Mega, control); treatment 2 (PLS1) contained 54 g Megalac/kg with 500 g PLS/d fed separately; treatment 3 (PLS2) contained no Megalac and 1000 g PLS/d fed separately. The PLS was considered as part of the overall concentrate allocation per d in maintaining an overall forage:concentrate value of 60:40 on a DM basis. Total dietary fat was formulated to be 0.07 of DM of which 0.04 was the test oil. Total intramuscular fatty acids (mg/100 g muscle) were decreased by 0.31 when feeding PLS2 compared with Mega (P<0.05). In neutral lipid, the PLS increased the proportion of 18 : 2n-6 and 18 : 3n-3 by 2.7 and 4.1 on diets PLS1 and PLS2 v. Mega, respectively. Similar responses were noted for these fatty acids in phospholipid. The amounts or proportions of 20 : 4n-6, 20 : 5n-3 or 22 : 6n-3 were not influenced by diet whereas the amounts and proportions of 22 : 4n-6 and 22 : 5n-3 in phospholipid were decreased with inclusion of the PLS. The amounts of the saturated fatty acids, 14 : 0, 16 : 0 and 18 : 0, in neutral lipid were on average 0.37 lower on treatment PLS2 compared with Mega. Feeding the PLS also decreased the proportion of 16 : 0 in neutral lipid. The amount of 18 : 1n-9 (P=0.1) and the amount and proportion of 18 : 1 trans (P<0.01) were lower on treatments PLS1 and PLS2 in neutral lipid and phospholipid. Conjugated linoleic acid (cis-9, trans-11) was not influenced by diet in the major storage fraction for this fatty acid, neutral lipid. The PUFA:saturated fatty acids value was increased markedly (x2.5) with inclusion of the PLS (P<0.001) while the Sigman-6 : n-3 value increased slightly (x1.2; P=0.015). The results suggest that the protected lipid used, which was rich in PUFA, had a high degree of protection from the hydrogenating action of rumen micro-organisms. The PLS resulted in meat with a lower content of total fat, decreased saturated fatty acids and much higher 18 : 2n-6 and 18 : 3n-3. The net result was a large shift in polyunsaturated: saturated fatty acids, 0.28 v. 0.08, on feeding PLS2 compared with Mega, respectively.


Schmid, K. E. and L. A. Woollett (2003). "Differential effects of polyunsaturated fatty acids on sterol synthesis rates in adult and fetal tissues of the hamster: consequence of altered sterol balance." Am J Physiol Gastrointest Liver Physiol 285(5): G796-803.

            Cholesterol is necessary for the proper growth and development of the fetus. Consequently, disruptions in cholesterol biosynthesis lead to abnormal fetal development. It has been shown that in cells exposed to polyunsaturated fatty acids (PUFA), the expressions of genes and activities of enzymes involved in cholesterol synthesis are reduced. Similarly, we found that adult male hamsters fed PUFA-enriched diets had an approximately 60% reduction in in vivo hepatic sterol synthesis rates. If fetal tissues respond to PUFA in the same manner as do adult livers, then maternal dietary PUFA could lead to a reduction in fetal sterol synthesis rates and possibly abnormal development. To investigate the impact of maternal dietary fatty acids on fetal sterol synthesis rates, female hamsters were fed diets enriched in various fatty acids before and throughout gestation. In vivo sterol synthesis rates were measured in fetuses at mid- and late gestation. At both gestational stages, dietary PUFA had no effect on fetal sterol synthesis rates. This lack of effect was not a consequence of a lack of PUFA enrichment in fetal fatty acids or the lack of PUFA receptor expression in the fetus. We hypothesize that the fetus may experience a dysregulation of sterol synthesis as the result of the fetus being in a negative sterol balance; the PUFA-induced suppression of sterol synthesis in the adult male hamster liver was ablated by creating a net negative sterol balance across the adult hepatocyte.


Scheinichen, D., M. Jankowski, et al. (2003). "Lack of influence of omega-3 fatty acid-enriched lipids on apoptosis and secondary necrosis of cultured human lymphocytes." Nutrition 19(5): 441-5.

            OBJECTIVE: The anti-inflammatory properties of parenteral nutrition might be improved by enrichment with omega-3 polyunsaturated fatty acids (PUFAs), which are responsible for the enhanced release of metabolites derived from eicosapentaenoic acid. Under physiologic conditions, lymphocyte populations are regulated by cellular mechanisms such as apoptosis. In contrast to cell death by necrosis, apoptosis does not induce an inflammatory response that might injure the host. METHODS: Apoptosis and necrosis of cultured human blood lymphocytes were investigated in vitro after incubation for 48 and 72 h with three lipid emulsions containing 50% medium-chain triacylglycerols. The lipid emulsions differed in the percentage of long-chain triacylglycerols, which were replaced in part by different amounts of omega-3 PUFA (8%, 20%, or 40%). Rates of apoptosis and necrosis of lymphocyte subpopulations were analyzed with a sensitive annexin V flow cytometric assay. RESULTS: After 48 and 72 h of incubation, time- and dose-dependent increases of apoptosis and necrosis, respectively, were found in all lymphocyte subsets regardless of the percentage of omega-3 PUFAs. CONCLUSIONS: Our results suggested that enrichment with omega-3 PUFAs in the tested lipid emulsions does not alter apoptosis and secondary necrosis of lymphocyte populations. Thus PUFAs may exert their functional effects through other mechanisms.


Schaur, R. J. (2003). "Basic aspects of the biochemical reactivity of 4-hydroxynonenal." Mol Aspects Med 24(4-5): 149-59.

            4-hydroxynonenal (HNE), a major lipid peroxidation product of n-6 polyunsaturated fatty acids, which was discovered by the late Hermann Esterbauer, is a remarkable trifunctional molecule. Both the hydroxy group and the conjugated system consisting of a C=C double bond and a carbonyl group contribute to the high reactivity of HNE. Most of the biochemical effects of HNE can be explained by its rapid reactions with thiol and amino groups. Among the primary reactants for HNE are the amino acids cysteine, histidine and lysine, which--either free or protein-bound--undergo readily Michael additions to the C=C bond. After this primary reaction, which confers rotational freedom to the C2-C3 bond, secondary reactions may occur involving the carbonyl and the hydroxy group. Primary amines may alternatively react with the carbonyl group to form Schiff bases. Reactions which do not fit into this scheme are the oxidation and the reduction respective of the carbonyl group and the epoxidation of the C=C double bond. Examples will be presented for the interaction of HNE with various classes of biomolecules such as proteins and peptides, lipids and nucleic acids and the biochemical consequences will be discussed.


Schafer, T., S. Ruhdorfer, et al. (2003). "Intake of unsaturated fatty acids and HDL cholesterol levels are associated with manifestations of atopy in adults." Clin Exp Allergy 33(10): 1360-7.

            BACKGROUND: The increase in allergic diseases is still unexplained. It was hypothesized that the intake of unsaturated fatty acids is a contributing cause of this development. We investigated the relationship between serum cholesterol levels, intake of polyunsaturated fatty acids (PUFA) and manifestations of atopy in a population-based setting. METHODS: A nested case-control study was performed within the population of the 3rd MONICA survey in Augsburg (Germany). The serum levels of total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol of 1537 adults (aged 28-78 years, response 61.4%) and the estimated intake of PUFA in a subset of 139 men were compared with the frequency of a doctor's diagnosis of asthma, allergic rhinoconjunctivitis (AR), atopic eczema (AE) and allergic sensitization as measured by skin prick and Radio Allergo Sorbent Test. FINDINGS: In bivariate analyses, we obtained a negative linear association between total and LDL cholesterol levels and the frequency of AR and sensitization, which was no longer significant after adjustment for important confounders. In contrast, positive linear associations were found between HDL cholesterol levels and AR and AE and, furthermore, between the intake of PUFA and allergic sensitization in men (P<0.01). After adjustment, an increasing risk for atopic diseases with increasing levels of HDL cholesterol and an increasing risk for allergic sensitization with increasing intakes of PUFA remained statistically significant. INTERPRETATION: There is indication that HDL cholesterol also plays a role in the complex interaction of fat intake, metabolism and the manifestation of atopy in adults. These findings may contribute to the understanding of time trends and regional differences of allergies.


Sayanova, O. V., F. Beaudoin, et al. (2003). "Identification of primula fatty acid delta 6-desaturases with n-3 substrate preferences." FEBS Lett 542(1-3): 100-4.

            Fatty acid Delta(6)-desaturation, the first committed step in C(20) polyunsaturated fatty acid biosynthesis, is generally considered not to discriminate between n-3 and n-6 substrates. We previously identified higher plant species that showed preferential Delta(6)-desaturation of n-3 C(18) fatty acid substrates. A polymerase chain reaction-based approach was used to isolate 'front-end' cytochrome b(5) fusion desaturases from Primula vialii Franchet and Primula farinosa L. Functional analysis in Saccharomyces cerevisiae identified fatty acid Delta(6)-desaturases with a strong specificity for the n-3 substrate alpha-linolenic acid (18:3 Delta(9,12,15)). These results indicate that the accumulation of octadecatetraenoic acid (18:4 Delta(6,9,12,15)) in planta is due to the activity of a novel n-3-specific fatty acid Delta(6)-desaturase.


Sarkadi-Nagy, E., M. C. Huang, et al. (2003). "Long chain polyunsaturate supplementation does not induce excess lipid peroxidation of piglet tissues." Eur J Nutr 42(5): 293-6.

            BACKGROUND: Addition of highly polyunsaturated fatty acids to infant formulas raises the possibility of increased lipid peroxidation. AIM OF THE STUDY: We determined the effects of increasing levels of dietary docosahexaenoic acid (DHA) and arachidonic acid (AA) on lipid peroxidation and peroxidative potential in piglet tissues. METHODS: Four groups of piglets (n = 6) were bottle-fed a formula containing one of four treatments: no long chain fatty acid (Diet 0) and three different levels of DHA/AA at 1-fold (0.3 %/0.6% FA; Diet 1) 2-fold (0.6 %/1.2% FA; Diet 2) and 5-fold (1.5%/3% FA; Diet 5) concentration used in some human infant formulas, and all with equal amount of vitamin E (5.7 IU/ 100 kcal formula) for four weeks. RESULTS: There were no significant differences between the groups in conjugated diene and glutathione (GSH) levels in the liver, and thiobarbituric acid-reactive substance (TBARS) in plasma. TBARS levels of the erythrocyte membranes increased in a dose-dependent manner when in vitro oxidation was induced with 10 mM hydrogen peroxide (H(2)O(2)) for 30 minutes. The TBARS levels of the liver homogenates of the Diet 5 and Diet 2 groups were significantly different than those of the membranes of the Diet 0 group when the in vitro oxidation was induced with H(2)O(2). CONCLUSION: The results show that dietary vitamin E effectively prevented lipid peroxidation at the LCP concentrations investigated and suggest that levels presently in infant formulas are sufficient.


Sanchez-Muniz, F. J., A. Carbajal, et al. (2003). "Nutritional assessment, health markers and lipoprotein profile in postmenopausal women belonging to a closed community." Eur J Clin Nutr 57 Suppl 1: S26-30.

            OBJECTIVE: To assess the dietary characteristics of a closed community and their relationship with several health markers and lipid and lipoprotein values in postmenopausal women. DESIGN: Energy and nutrient intake, serum lipids, lipoproteins, antioxidants, peroxides and low-density lipoprotein (LDL) peroxides in addition to several health markers were measured in a closed, postmenopausal female community consuming a diet without meat, meat products and alcoholic beverages. SETTING: Departamento de Nutricion and Seccion Departamental de Quimica Analitica and Escuela de Especializacion de Analisis Clinicos, Universidad Complutense de Madrid, Spain and Lerma, Burgos, Spain. RESULTS: Cereals, vegetables, legumes and fruit, together with milk and eggs, constituted the most important ingredients of the diet consumed. Dietary carbohydrates contributed 42%en and lipids 46.4%en. The SFA/MUFA/PUFA ratio was 1/2/1 and the n-3/n-6 ratio 0.05 (SFA=saturated fatty acids, MUFA=monounsaturated fatty acids, PUFA=polyunsaturated fatty acids). The study community diet was monotonous and made for possible deficiencies of iron, magnesium, zinc, vitamin B(6) and vitamin D, in variable proportions. Routine biochemical and haematological normality markers indicate that only one woman presented hyperglycaemia and hyperuricaemia. Two women had haemoglobin levels <12 g/dl, but their mean corpuscular volume or mean corpuscular haemoglobin was normal. The prevalence of high cholesterol values (>6.21 mmol/l) was 42.8%, while that of high LDL-cholesterol levels (>3.88 mmol/l) was 35.7%, but none of the women displayed levels of high-density lipoprotein (HDL)-cholesterol <1.16 mmol/l, triglycerides >1.2 mmol/l or an LDL-cholesterol/HDL-cholesterol ratio>3. Only one woman had apolipoprotein (Apo) B levels >1.5 g/l, while most of the women presented Apo B values <1.2 g/l and an ApoA-1/ApoB ratio &<1.1. Plasma and LDL-peroxide levels, together with the tocopherol and carotene intakes, suggest a good antioxidant status in this population. CONCLUSIONS: The diet of the study group seems compatible with a healthy life-profile and permits a more-than-acceptable degree of cardiovascular disease protection. However, the consumption of certain nutrients should be improved.


Samuni, A. M. and Y. Barenholz (2003). "Site-activity relationship of nitroxide radical's antioxidative effect." Free Radic Biol Med 34(2): 177-85.

            A relatively new strategy in preventing oxidative damage employs cyclic nitroxides. These stable radicals have been widely used as biophysical probes, spin labels, and are currently tested as contrast agents for nuclear magnetic resonance imaging. Nitroxides were found to protect cells, organs, and whole animals against diverse oxidative insults. The present study concentrated on comparing the antioxidative activity of nitroxides against oxidative damage, initiated either in the lipid or aqueous phase, to egg phosphatidylcholine acyl chains (13.4% polyunsaturated fatty acids) in small unilamellar vesicles. We determined the lipophilicity and liposome-membrane/aqueous-medium partition coefficient for several nitroxides and compared their specific protective effects. The aim was to study the relation between nitroxides' concentration, location in the lipid bilayer, and their protection against oxidative damage. Both 6-membered- and 5-membered-ring nitroxides were studied for: (i) partitioning between the lipid bilayer and the aqueous phase (nitroxides were quantified using EPR spectroscopy); (ii) the intrabilayer distribution, using three different fluorescent probes of known location of their fluorophors in the lipid bilayer; and (iii) the specific antioxidative effect (protection per concentration) against radicals formed in a liposomal dispersion. The radicals were generated using the thermolabile, radical-generating compounds 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) in the aqueous phase, and 2,2'-azobis (2,4-dimethyl-valeronitrile) (AMVN) in the lipid phase. The results show that nitroxides react, in a concentration-dependent manner, with deleterious species at their formation sites, both in the aqueous and the lipid phase, and that their specific protective effects for the lipophilic target, the lipid bilayer, are similar for both the lipophilic and the hydrophilic nitroxides.


Salvatori, G., G. Maiorano, et al. (2003). "Control of dietary energy level and dl-alpha-tocopheryl acetate treatment can improve the lipid composition of lamb meat." Int J Vitam Nutr Res 73(3): 171-9.

            A diet rich in saturated fatty acids promotes plasmatic cholesterol levels and coronary disease in humans, whereas a high intake of polyunsaturated fatty acids reduces atheromatous plaque thickness. This study aimed at establishing a dietary energy level, which combined with intramuscular vitamin E treatment, would improve the nutritional lipid quality and shelf-life of lamb meat. Twenty male lambs were evaluated in a 2 x 2 factorial experiment: they were fed a low- and normal-energy diet (0.85 and 1.00 UFV NE/kg DM, respectively), and were injected intramuscularly with 0 and 150 IU dl-alpha-tocopheryl acetate/weekly for eight weeks. Thereafter, total fat, cholesterol, fatty acid profile, and lipostability were measured in meat samples. Meat total fat was significantly reduced by low energy intake diet and vitamin E administration. Cholesterol was significantly lower in meat from lambs fed the 0.85 UFV NE/kg DM diet. Vitamin E treatment increased linoleic acid percent values and decreased myristic acid levels. Moreover, linoleic acid percentage was inversely correlated with muscle total fat concentration. Meat sensitivity to lipoperoxidation was inversely correlated with muscle vitamin E concentration. This study demonstrates that nutritional characteristics and shelf-life of meat benefit from a low-energy diet and intramuscular vitamin E treatment.


Sala Vila, A., A. I. Castellote-Bargallo, et al. (2003). "High-performance liquid chromatography with evaporative light-scattering detection for the determination of phospholipid classes in human milk, infant formulas and phospholipid sources of long-chain polyunsaturated fatty acids." J Chromatogr A 1008(1): 73-80.

            We developed and validated a new high-performance liquid chromatographic method for the separation of phospholipid classes in human milk, infant formulas and phospholipidic sources of long-chain polyunsaturated fatty acids (LC-PUFAs) used in paediatric nutrition. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine and sphingomyelin were separated in less than 25 min using an Extrasil silica column (150 x 4.0 mm I.D., 3-microm particle size) by isocratic elution with a mixture of isopropanol-hexane-water. Phospholipids were determined by an evaporative light-scattering detector. Several chromatographic conditions were assayed to optimise the method, whose suitability is shown by the detection limits, linearity ranges and precision rates obtained. The main advantages of the proposed method are its speed and the direct determination of the main phospholipids present in human milk, infant formulas and the phospholipid sources of LC-PUFAs used in paediatric nutrition.


Saether, T., T. N. Tran, et al. (2003). "Expression and regulation of delta5-desaturase, delta6-desaturase, stearoyl-coenzyme A (CoA) desaturase 1, and stearoyl-CoA desaturase 2 in rat testis." Biol Reprod 69(1): 117-24.

            In mammalian cells, essential polyunsaturated fatty acids (PUFAs) are converted to longer PUFAs by alternating steps of elongation and desaturation. In contrast to other PUFA-rich tissues, the testis is continuously drained of these fatty acids as spermatozoa are transported to the epididymis. Alteration of the germ cell lipid profile from spermatogonia to condensing spermatids and mature spermatozoa has been described, but the male gonadal gene expression of the desaturases, responsible for the PUFA-metabolism, is still not established. The focus of this study was to characterize the expression and regulation of stearoyl-CoA desaturase 1 (SCD1), stearoyl-CoA desaturase 2 (SCD2), and Delta5- and Delta6-desaturase in rat testis. Desaturase gene expression was detected in testis, epididymis, and separated cells from seminiferous tubulus using Northern blot analysis. For the first time, SCD1 and SCD2 expression is demonstrated in rat testis and epididymis, both SCDs are expressed in epididymis, while testis mainly contains SCD2. Examination of the testicular distribution of Delta5- and Delta6-desaturase and SCD1 and SCD2 shows that all four desaturases seem to be localized in the Sertoli cells, with far lower expression in germ cells. In light of earlier published results showing that germ cells are richer in PUFAs than Sertoli cells, this strengthens the hypothesis of a lipid transport from the Sertoli cells to the germ cells. As opposed to what is shown in liver, Delta5- and Delta6-desaturase mRNA levels in Sertoli cells are up-regulated by dexamethasone. Furthermore, dexamethasone induces SCD2 mRNA. Insulin also up-regulates these three genes in the Sertoli cell, while SCD1 mRNA is down-regulated by both insulin and dexamethasone. Delta5- and Delta6-desaturase, SCD1, and SCD2 are all up-regulated by FSH. A similar up-regulation of the desaturases is observed when treating Sertoli cells with (Bu)2cAMP, indicating that the desaturase up-regulation observed with FSH treatment results from elevated levels of cAMP. Finally, testosterone has no influence on the desaturase gene expression. Thus, FSH seems to be a key regulator of the desaturase expression in the Sertoli cell.


Rukkumani, R., M. Sri Balasubashini, et al. (2003). "Protective effects of curcumin and photo-irradiated curcumin on circulatory lipids and lipid peroxidation products in alcohol and polyunsaturated fatty acid-induced toxicity." Phytother Res 17(8): 925-9.

            Alcohol is a neurotoxin associated with significant morbidity and mortality. Ethanol is found to induce a dose dependent increase in lipid peroxidation (LPO). The elevation in lipid peroxidative products and the loss of antioxidant defense potential are enhanced when alcohol is taken along with polyunsaturated fatty acid (PUFA) or heated PUFA. The present study was undertaken to evaluate the effects of curcumin and photo-irradiated curcumin on alcohol and PUFA induced LPO and lipid pro fi les in plasma. The levels of vitamin C and E were decreased significantly in alcohol + raw as well as heated PUFA groups. The treatment with curcumin and photo-irradiated curcumin (IC) increased their levels significantly. The increase was more significant in the IC group than the curcumin group. The levels of cholesterol, phospholipids (PL), triglycerides (TG), free fatty acids (FFA), thiobarbituric acid reactive substances (TBARS) and hydroperoxides (HP) were increased significantly in alcohol + raw as well as heated PUFA groups and the treatment with curcumin and IC, brought back the levels. But the IC reduced the levels more significantly than curcumin. Thus, our results indicate that IC is a more potent antioxidant than curcumin.


Rozenberg, O., D. M. Shih, et al. (2003). "Human serum paraoxonase 1 decreases macrophage cholesterol biosynthesis: possible role for its phospholipase-A2-like activity and lysophosphatidylcholine formation." Arterioscler Thromb Vasc Biol 23(3): 461-7.

            OBJECTIVE: Human serum paraoxonase 1 (PON1) activity is inversely related to the risk of developing an atherosclerotic lesion, which contains cholesterol-loaded macrophage foam cells. To assess a possible mechanism for this relationship, we analyzed the effect of PON1 on cellular cholesterol biosynthesis. METHODS AND RESULTS: Mouse peritoneal macrophages (MPMs) were harvested from PON1-deficient mice (PON1o and PON1o/Eo mice on the genetic background of C57BL/6J and Eo mice, respectively). PON1o/Eo mice exhibited a significantly 51% increased atherosclerotic lesion area and 35% increased macrophage cholesterol content compared with control E degrees mice. In parallel, macrophage cholesterol biosynthesis rates were increased in PON1-deficient mice MPMs by 50% compared with their controls. Incubation of macrophages with human PON1 revealed a dose-dependent inhibitory effect (up to 84%) on macrophage cholesterol biosynthesis. We demonstrated a PON1 phospholipase-A2-like activity on MPMs, evidenced by release of polyunsaturated fatty acids and formation of lysophosphatidylcholine. On incubation of macrophages with lysophosphatidylcholine, a dose-dependent inhibition (up to 40%) of cellular cholesterol biosynthesis was noted. The inhibitory effect of PON1 on macrophage cholesterol biosynthesis was shown to be downstream to mevalonate, probably at the lanosterol metabolic point. CONCLUSIONS: PON1 inhibits macrophage cholesterol biosynthesis and atherogenesis probably through its phospholipase-A2-like activity.


Royo-Bordonada, M. A., L. Gorgojo, et al. (2003). "Food sources of nutrients in the diet of Spanish children: the Four Provinces Study." Br J Nutr 89(1): 105-14.

            The aim of the present study was to assess the principal food sources of energy and nutrients among Spanish children. We used a cross-sectional study design, based on results obtained from a food-frequency questionnaire. The sample included 1112 children, aged 6-7 years, from Cadiz, Madrid, Orense and Murcia, Spain. Children were selected through random cluster-sampling in schools. We analysed the percentage contributed by each food item to total energy and nutrient intake. The most important food sources were: white bread in the case of carbohydrate (13.4 %); olive oil in the case of total lipids (18.3 %) and monounsaturated fatty acids (29.2 %); whole milk in the case of protein (10.2 %) and saturated fatty acids (14.9 %); chips (French fried potatoes) in the case of polyunsaturated fatty acids (30.4 %). The greatest proportion of Na, consumed in excess, came from salt added to meals. Ham ranked second as a source of saturated fats. Fruits and green leafy vegetables proved to have great relevance as sources of fibre and vitamins, though with regard to the latter, it was observed that fortified foods (breakfast cereals, dairy products, fruit juices, etc.) had come to play a relevant role in many cases. In conclusion, the nutritional profile of Spanish school-aged children aged 6-7 years could be improved by nutritional policies targeted at limiting their consumption of ham (cured or cooked) and of salt added to meals, replacing whole milk with semi-skimmed milk, encouraging the consumption of products rich in complex carbohydrates already present in children's diets (bread, pasta, rice) and promoting less fatty ways of cooking food.


Rouzer, C. A. and L. J. Marnett (2003). "Mechanism of free radical oxygenation of polyunsaturated fatty acids by cyclooxygenases." Chem Rev 103(6): 2239-304.


Rouvinen-Watt, K. (2003). "Nursing sickness in the mink--a metabolic mystery or a familiar foe?" Can J Vet Res 67(3): 161-8.

            Nursing sickness, the largest single cause of mortality in adult female mink (Mustela vison), is an example of a metabolic disorder, which develops when the demands for lactation require extensive mobilization of body energy reserves. The condition is characterized by progressive weight loss, emaciation, and dehydration with high concentrations of glucose and insulin in the blood. Morbidity due to nursing sickness can be as high as 15% with mortality around 8%, but the incidence is known to vary from year to year. Stress has been shown to trigger the onset of the disease and old females and females with large litters are most often affected. Increasing demand for gluconeogenesis from amino acids due to heavy milk production may be a predisposing factor. Glucose metabolism is inextricably linked to that of protein and fats. In obesity (or lipodystrophy), the ability of adipose tissue to buffer the daily influx of nutrients is overwhelmed (or absent), interfering with insulin-mediated glucose disposal and leading to insulin resistance. Polyunsaturated fatty acids of the n-3 family play an important role in modulating insulin signalling and glucose uptake by peripheral tissue. The increasing demand on these fatty acids for milk fat synthesis towards late lactation may result in deficiency in the lactating female, thus impairing glucose disposal. It is suggested that the underlying cause of mink nursing sickness is the development of acquired insulin resistance with 3 contributing key elements: obesity (or lipodystrophy), n-3 fatty acid deficiency, and high protein oxidation rate. It is recommended that mink breeder females be kept in moderate body condition during fall and winter to avoid fattening or emaciation. A dietary n-3 fatty acid supplement during the lactation period may be beneficial for improved glycemic control. Lowering of dietary protein reduces (oxidative) stress and improves water balance in the nursing females and may, therefore, prevent the development and help in the management of nursing sickness. It is also surmised that other, thus far unexplained, metabolic disorders seen in male and female mink may be related to acquired insulin resistance.


Rousseau, D., C. Helies-Toussaint, et al. (2003). "Dietary n-3 PUFAs affect the blood pressure rise and cardiac impairments in a hyperinsulinemia rat model in vivo." Am J Physiol Heart Circ Physiol 285(3): H1294-302.

            The cardiovascular consequences of eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-specific intake were evaluated in vivo in a hyperinsulinemia (HI) model induced by dietary fructose intake. Wistar rats were fed a diet containing (or not for control) either EPA or DHA. The rise in blood pressure (BP), heart rate, and ECG were continuously monitored using an intra-abdominal telemetry system. The myocardial phospholipid fatty acid profile was significantly affected by DHA intake but less by EPA intake. The data indicated a reduced rise in BP in both DHA and EPA HI groups compared with controls. This result was confirmed by tail-cuff measurement after 5 wk [133.3 +/- 1.67 and 142.5 +/- 1.12 mmHg in n-3 polyunsaturated fatty acid (PUFA) and control groups, respectively], whereas n-3 PUFA did not affect BP in non-HI rats (116.3 +/- 3.33 mmHg). The heart rate was lower in the HI DHA group than in the other two dietary HI groups. Moreover, DHA induced a significantly shorter QT interval. It is concluded that the cardioactive component of fish oils is DHA through a mechanism that may involve the cardiac adrenergic system.


Ross, B. M., I. McKenzie, et al. (2003). "Increased levels of ethane, a non-invasive marker of n-3 fatty acid oxidation, in breath of children with attention deficit hyperactivity disorder." Nutr Neurosci 6(5): 277-81.

            Attention deficit hyperactivity disorder (ADHD) comprises a range of behavioural problems including inattention, hyperactivity and impulsivity. Diagnosis and treatment of the disorder is made difficult due to its unknown biological basis. Several studies have identified abnormalities in membrane fatty acids in some subjects with ADHD, and some success has been reported using lipid therapies. We have measured exhalant ethane levels, a non-invasive measure of oxidative damage to n-3 fatty acids, to probe biochemical alterations in ADHD. Patients with ADHD (N = 10) had higher levels of ethane in exhalant than in healthy volunteers (N = 12) with approximately 50% of ADHD cases being above the control range. In contrast, levels of butane, a marker of protein oxidation, were unaltered. Our data, although preliminary, suggests that some patients with ADHD have higher rates of oxidative breakdown of n-3 polyunsaturated fatty acids (PUFAs). Such a biochemical abnormality may underlie the previously observed fatty acid deficiencies, as well as providing further rationale for the use of anti-oxidant and/or lipid supplementation therapy in the treatment of ADHD. Larger studies of ADHD using this non-invasive assessment of oxidative stress appear warranted.


Ross, J. A., J. P. Maingay, et al. (2003). "Eicosapentaenoic acid perturbs signalling via the NFkappaB transcriptional pathway in pancreatic tumour cells." Int J Oncol 23(6): 1733-8.

            In addition to various roles in membrane structure and metabolism, polyunsaturated fatty acids have effects on signal transduction and on the regulation of gene expression. Eicosapentaenoic acid (EPA) is an omega-3 fatty acid which is known to induce cell cycle arrest and apoptosis in pancreatic tumour cells. NFkappaB is a key transcription factor regulating genes involved in the immune response and has been implicated in apoptotic pathways. In this study we investigated the effect of eicosapentanoic acid on the NFkappaB pathway in pancreatic tumour cells. The pancreatic cell line MIA PaCa2 was incubated in the presence of the fatty acids EPA (n-3), arachidonic acid (AA, n-6) or oleic acid (OA, n-9) before pulsing with TNF to provide a kinetic assessment of NFkappaB activation and IkappaBalpha degradation. Pre-incubation of pancreatic cells with EPA or AA for 2 h before pulsing with TNF preserved IkappaBalpha but did not prevent NFkappaB activation. Indeed, NFkappaB activation was prolonged after exposure to EPA. N-acetyl-L-cysteine did not influence the effect of EPA on TNF-stimulated IkappaBalpha degradation. These results suggest that the omega-3 fatty acid EPA perturbs the NFkappaB pathway by a novel mechanism. This mechanism may be important in delineating alternative pathways to NFkappaB activation.


Rosenstein, E. D., L. J. Kushner, et al. (2003). "Pilot study of dietary fatty acid supplementation in the treatment of adult periodontitis." Prostaglandins Leukot Essent Fatty Acids 68(3): 213-8.

            The anti-inflammatory effects of both n-3 and n-6 polyunsaturated fatty acids (PUFA) have been demonstrated in vitro and in many disease states, in particular in the treatment of rheumatoid arthritis. The benefit of n-3 PUFA supplementation has been documented in animal models of periodontal inflammation and a trend towards reduced inflammation has been seen in human experimental gingivitis. The purpose of this study was to examine the potential anti-inflammatory effects of PUFA supplementation, by administration of fish oil as a source of the n-3 PUFA, eicosapentaenoic acid, and borage oil as a source of the n-6 PUFA, gamma-linolenic acid (GLA), to adults with periodontitis. Thirty adult human subjects with periodontitis were administered either fish oil 3000 mg daily; borage oil 3000 mg daily; fish oil 1500 and borage oil 1500 mg daily, or placebo. The modified gingival index, the plaque index (PI), periodontal probing depths and beta-glucuronidase levels in gingival crevicular fluid were measured at baseline and after 12 weeks of treatment. Improvement in gingival inflammation was observed in subjects treated with borage oil (P<0.016), with a trend apparent in subjects treated with fish oil or a combination of PUFA. There was no statistically significant improvement in PI, although a trend was apparent in those receiving borage oil. Improvement in probing depth was seen in those subjects treated with either fish oil alone or borage oil alone, but statistical significance was only seen for the comparison of borage oil and placebo (P<0.044). No change was seen in gingival crevicular fluid (GCF) beta-glucuronidase levels. The use of borage oil supplementation, a source of the n-6 PUFA, GLA, can have beneficial effects on periodontal inflammation. n-6 PUFA supplementation seemed to offer more impressive results than either n-3 PUFA supplementation or the combination of lower doses of the two supplements. Additional studies will be necessary to more fully assess the potential of these agents to favorably affect periodontal inflammation.


Rosenberger, T. A., N. E. Villacreses, et al. (2003). "Brain lipid metabolism in the cPLA2 knockout mouse." J Lipid Res 44(1): 109-17.

            We examined brain phospholipid metabolism in mice in which the cytosolic phospholipase A(2) (cPLA(2,) Type IV, 85 kDa) was knocked out (cPLA(2)(-/-) mice). Compared with controls, these mice demonstrated altered brain concentrations of several phospholipids, reduced esterified linoleate, arachidonate, and docosahexaenoate in choline glycerophospholipid, and reduced esterified arachidonate in phosphatidylinositol. Unanesthetized cPLA(2)(-/-) mice had reduced rates of incorporation of unlabeled arachidonate from plasma and from the brain arachidonoyl-CoA pool into ethanolamine glycerophospholipid and choline glycerophospholipid, but elevated rates into phosphatidylinositol. These differences corresponded to altered turnover and metabolic loss of esterified brain arachidonate. These results suggests that cPLA(2) is necessary to maintain normal brain concentrations of phospholipids and of their esterified polyunsaturated fatty acids. Reduced esterified arachidonate and docosahexaenoate may account for the resistance of the cPLA(2)(-/-) mouse to middle cerebral artery occlusion, and should influence membrane fluidity, neuroinflammation, signal transduction, and other brain processes.


Rosell, M. S., M. L. Hellenius, et al. (2003). "Associations between diet and the metabolic syndrome vary with the validity of dietary intake data." Am J Clin Nutr 78(1): 84-90.

            BACKGROUND: Underreporting is a common problem in dietary surveys. Few studies have shown the implication of this when investigating diet-disease relations. OBJECTIVE: We investigated how underreporting affects the associations between dietary factors and the metabolic syndrome. DESIGN: Dietary intake measured with a 7-d food record, fasting insulin concentrations, and other variables of the metabolic syndrome were assessed in a cross-sectional study of 301 healthy men aged 63 y. Biological markers for intakes of protein, sodium, and potassium were measured in 24-h urine samples. Underreporters (URs, n = 88) were identified by Goldberg's equation, which compares energy intake with energy expenditure, both expressed as multiples of the basal metabolic rate. Physical activity level was estimated, and individual cutoffs were calculated. RESULTS: The URs had higher nutrient and food densities in their diet than did the non-URs, which suggested that they followed a healthier diet. The URs had a higher prevalence of the metabolic syndrome than did the non-URs (18% and 9%, respectively; P = 0.029). The biological markers confirmed a low validity of the dietary data in the URs. The correlations between fasting insulin concentrations, a central component of the metabolic syndrome, and the intakes of polyunsaturated fats, n-6 fats, and fat from milk products were stronger in the URs than in the non-URs, which indicates that inaccurate data can introduce spurious associations. CONCLUSION: The association between diet and fasting insulin differed between URs and non-URs in this study of 301 healthy men aged 63 y. If URs are not identified and excluded or treated separately in studies in nutritional epidemiology, spurious diet-disease relations may be reported.


Rorvik, K. A., A. Dehli, et al. (2003). "Synergistic effects of dietary iron and omega-3 fatty acid levels on survival of farmed Atlantic salmon, Salmo salar L., during natural outbreaks of furunculosis and cold water vibriosis." J Fish Dis 26(8): 477-85.

            The present study demonstrates that farmed Atlantic salmon, Salmo salar, health is positively and significantly affected by synergistic effects between very long-chain polyunsaturated fatty acids of the n-3 family eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) and iron, where positive effects of high dietary levels of EPA/DHA are enhanced when combined with low levels of iron. Based on cumulative mortalities in the different experimental groups, relative percentage of survival (RPS) for the high EPA/DHA-low iron group was 70% during an outbreak of furunculosis and 96% during an outbreak of cold water vibriosis compared with the controls. A non-additive effect between EPA/DHA and iron was confirmed by statistical analyses that revealed a significant effect of EPA/DHA alone and an interaction of iron with EPA/DHA. Liver cell cultures treated with EPA/DHA revealed that the synergistic effect could be related to an EPA/DHA dependent regulation of mRNA for proteins important for transport (transferrin) and storage (ferritin) of iron in the salmon. In keeping with this finding, the transcriptional down-regulation of iron metabolism in vitro was reflected in decreased in vivo iron stores with increasing levels of dietary EPA/DHA. Hence, to avoid overloading of the iron transport/storage-systems resulting in increased susceptibility to bacterial infections, high levels of dietary EPA/DHA should be accompanied by low levels of dietary iron.


Rontani, J. F., A. Mouzdahir, et al. (2003). "Production of a polyunsaturated isoprenoid wax ester during aerobic metabolism of squalene by Marinobacter squalenivorans sp. nov." Appl Environ Microbiol 69(7): 4167-76.

            This paper describes the production of 5,9,13-trimethyltetradeca-4E,8E,12-trienyl-5,9,13-trimethyltetradeca-4E,8E ,12-trienoate during the aerobic degradation of squalene by a Marinobacter strain, 2Asq64, isolated from the marine environment. A pathway involving initial cleavage of the C(10)-C(11) or C(14)-C(15) double bonds of the squalene molecule is proposed to explain the formation of this polyunsaturated isoprenoid wax ester. The isoprenoid wax ester content reached 1.1% of the degraded squalene at the mid-exponential growth phase and then decreased during the stationary phase. The wax ester content increased by approximately threefold in N-limited cultures, in which the ammonium concentration corresponds to conditions often found in marine sediments. This suggests that the bacterial formation of isoprenoid wax esters might be favored in such environments. The bacterial strain is then characterized as a member of a new species, for which we propose the name Marinobacter squalenivorans sp. nov.


Rollin, X., J. Peng, et al. (2003). "The effects of dietary lipid and strain difference on polyunsaturated fatty acid composition and conversion in anadromous and landlocked salmon (Salmo salar L.) parr." Comp Biochem Physiol B Biochem Mol Biol 134(2): 349-66.

            Five experimental diets containing different proportions of olive, sunflower and linseed oils were used in a 55-day feeding trial on both anadromous and landlocked parr of Atlantic salmon (Salmo salar) of the same age, in order to study the effects of diet and strain on growth and fatty acid composition and absolute gains in fish whole body triacylglycerols (TAG) and phospholipids (PL). Growth rate was higher in landlocked than in anadromous parr, but not between the different diets. By contrast, the effect of diet on whole body fatty acid composition was much more pronounced than that of strain difference. The fatty acids deposition results establish significant (P<0.05) positive correlations and linear relationships between the percentage of several fatty acids (18:1n-9, 18:2n-6, 18:3n-3) in dietary lipids and their absolute gains in whole body TAG and PL of both stocks. They also indicate the selective deposition of 18:1n-9 compared with linoleic acid (LLA) and linolenic acid (LNA). Finally, the results suggest the occurrence of the conversion of LLA and LNA to long-chain polyunsaturated fatty acids, its stimulation by increased substrate availability, a significantly higher n-3 and n-6 polyunsaturated fatty acids conversion capacity in landlocked than in anadromous parr and a strong genetic influence on docosahexaenoic acid content in salmon parr PL.


Rohrmann, S. and G. Klein (2003). "Validation of a short questionnaire to qualitatively assess the intake of total fat, saturated, monounsaturated, polyunsaturated fatty acids, and cholesterol." J Hum Nutr Diet 16(2): 111-7.

            BACKGROUND: To validate a self-administered 20-item short questionnaire (SQ) for classifying individuals according to their intake of total fat, saturated (SFA), monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA), as well as cholesterol. METHODS: The SQ was sent to a randomly selected subsample of 300 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) in Heidelberg. The SQ was sent back by 244 participants (52.5% women, 47.5% men). Intake of total fat, SFA, MUFA, PUFA, and cholesterol was calculated from a 148-item food frequency questionnaire (FFQ). The intake was compared with the scores computed from the SQ. RESULTS: Spearman's correlation coefficient between the intake estimated from the FFQ and the score from the SQ ranged from r = 0.29 (PUFA) to r = 0.56 (cholesterol). When the participants were assigned to quartiles of intake according to both methods 29-42% were classified into the same quartile, 1-7% of the participants were grossly misclassified. CONCLUSIONS: The SQ demonstrated a good validity with respect to SFA and cholesterol and an acceptable validity with respect to total fat and MUFA, while the results are less good for PUFA. The SQ can be used to classify persons according to their intake into categories of intake.


Rohrmann, S. and G. Klein (2003). "Development and validation of a short food list to assess the intake of total fat, saturated, mono-unsaturated, polyunsaturated fatty acids and cholesterol." Eur J Public Health 13(3): 262-8.

            BACKGROUND: The aim of this study was the development and validation of a short list of food items to assess the intake of total fat, saturated, mono-unsaturated, polyunsaturated fatty acids, and cholesterol. The short list should be able to correctly classify persons according to their intake. METHODS: A short list of 20 food items was selected out of 1009 seven-day food records by means of the variance-based method Max_r. This list was validated using data from a further 479 persons who completed seven-day food records (validation sample 1, VS1) as well as a food frequency questionnaire (validation sample 2, VS2). The intake of total fat, different fatty acids, and cholesterol from the complete VS1 (VS1(complete)) and from the complete VS2 (VS2(complete)), respectively, was computed. Further, the intake in VS1 (VS1(short)) as well as in VS2 (VS2(short)) using only the 20 food items on the short list were calculated. RESULTS: Pearson correlation coefficients between the intake calculated from the items on the short list and the nutrient intake calculated from the full instrument in VS1 and VS2, respectively, were r = 0.81-0.91. In a quartile's cross-classification 53.4-64.1% of the participants were assigned to the same quartile. When comparing VS1(complete) with VS2(short), neither correlation coefficients nor the cross-classification differ much from the comparison of VS1(complete) with VS2(complete). CONCLUSIONS: The short list shows good results in both validation samples. Thus, the short list can assess the variability of fat intake and classify persons according to their intake.


Rodriguez, M., S. Funke, et al. (2003). "Plasma fatty acids and [13C]linoleic acid metabolism in preterm infants fed a formula with medium-chain triglycerides." J Lipid Res 44(1): 41-8.

            Most preterm infant formulas contain medium-chain triacylglycerols (MCT), but the effects of MCT on polyunsaturated fatty acid status and metabolism are controversial. Thus, we studied the effects of MCT on linoleic acid metabolism using stable isotopes. Enterally fed preterm infants were randomized to receive for 7 days 40% of fat as MCT (n = 10) or a formula without MCT (n = 9). At study day 5, infants received orally 2 mg/kg body weight of (13)C-labeled linoleic acid. Fatty acids in plasma lipid classes and (13)C enrichment of phospholipid fatty acids were measured and tracer oxidation was monitored. Compared with the control group, the MCT group showed lower breath (13)CO(2) and higher plasma triacylglycerol contents of octanoic acid, of decanoic acid, and of total long-chain polyunsaturated fatty acids (57.1 +/- 4.4 micro mol/l vs. 37.9 +/- 4.8 micro mol/l, P < 0.01). Concentrations of several polyunsaturated fatty acids in plasma phospholipids and non esterified fatty acids were higher in the MCT group. (13)C concentrations in phospholipid n-6 fatty acids indicated no difference in the relative conversion of linoleic to arachidonic acid. We conclude that oral MCT effectively reduce polyunsaturated fatty acid and long chain polyunsaturated fatty acid oxidation in preterm infants without compromising endogenous n-6 long chain polyunsaturated fatty acid synthesis.


Rocquelin, G., S. Tapsoba, et al. (2003). "Human milk fatty acids and growth of infants in Brazzaville (The Congo) and Ouagadougou (Burkina Faso)." Public Health Nutr 6(3): 241-8.

            OBJECTIVE: To estimate the role of human milk n-6 and n-3 polyunsaturated fatty acids (PUFA) in term infant growth in two African urban populations. DESIGN: Observational study. Weight gains at 5 months of age and dietary habits were compared between Congolese infants (n=102) and Burkinabe infants (n=101). Socio-economic status and anthropometry of the mothers were also recorded. SETTING: One suburban district in Brazzaville (capital of The Congo) and one in Ouagadougou (capital of Burkina Faso). SUBJECTS: Two random samples of nursing mothers and their 5-month-old infants. RESULTS: All infants were born at term and there was no difference in birth weights. At 5 months of age, infants in Ouagadougou were thinner but not shorter than their counterparts in Brazzaville (average weight gain (standard deviation): 614 (168) g month-1 vs. 720 (176) g month-1; P= 0.0001). Drastic differences were found in infant diets with regard to extra fluid intake and n-6 and n-3 PUFA concentrations in breast milk. In Ouagadougou, all infants were given fluids other than milk from birth. Breast milk had highly unbalanced 18:2n-6/18:3n-3 and n-6/n-3 long-chain PUFA ratios (53:1 and 5:1, respectively). In Brazzaville, half of the infants received fluids other than milk, and breast milk showed balanced 18:2n-6/18:3n-3 and n-6/n-3 long-chain PUFA ratios (12:1 and 1:1, respectively). A non-linear relationship between 18:2n-6/18:3n-3 ratio and growth was established in Brazzaville (P= 0.0027). The 18:2n-6/18:3n-3 ratio adjusted with covariates had an even more significant effect on weight gain (P= 0.0011). Applying the same model in Ouagadougou did not show such a relation. CONCLUSION:: Data strongly suggest that a balanced ratio of 18:2n-6/18:3n-3 (between 5:1 and 15:1) in breast milk leads to higher weight gain of infants during the first 5 months of life.


Rocha, J. M., J. E. Garcia, et al. (2003). "Growth aspects of the marine microalga Nannochloropsis gaditana." Biomol Eng 20(4-6): 237-42.

            Nannochloropsis is well appreciated in aquaculture due to its nutritional value and the ability to produce valuable chemical compounds, such as pigments (zeaxanthin, astaxanthin...) and polyunsaturated fatty acids (EPA). Commercial exploitation needs high cell densities but the low growth rate and the small size of cells are practical difficulties. To increase biomass concentration the positive effect of several factors was evident: (i) pH approximately 8 control (with dilute Tris-HCl buffer); (ii) the continuous illumination (no evidence of photo-inhibition was observed); (iii) a quite large temperature range (25+/-5 degrees C); (iv) the presence of organic carbon source (with the danger of contamination); (v) the presence of urea as an additional nitrogen source (10 mM); (vi) a small air flow rate with large bubbles can be more efficient for CO(2) mass transfer (associated to reduced shearing).


Robinson, B. S., D. A. Rathjen, et al. (2003). "Inhibition of neutrophil leukotriene B4 production by a novel synthetic N-3 polyunsaturated fatty acid analogue, beta-oxa 21:3n-3." J Immunol 171(9): 4773-9.

            We recently reported the synthesis and anti-inflammatory properties of a novel long chain polyunsaturated fatty acid (PUFA) with an oxygen atom in the beta-position, beta-oxa-21:3 n-3 (Z,Z,Z)-(octadeca-9,12,15-trienyloxy) acetic acid). Our data, from studies aimed at elucidating the mechanism of its action, show that pretreatment of human neutrophils with the beta-oxa-PUFA substantially depresses the production of leukotriene B(4) (LTB(4)) in response to calcium ionophore, A23187, comparable to standard leukotriene inhibitors such as zileuton and nordihydroguaiaretic acid. Interestingly, the n-6 equivalent, beta-oxa 21:3 n-6, is also a strong inhibitor of LTB(4) production. In contrast, naturally occurring PUFA only slightly reduce, for eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids, or increase, for arachidonic acid (20:4n-6), the formation of LTB(4). The parent beta-oxa-21:3n-3 molecule, rather than its derivatives (methyl ester, saturated, monohydroperoxy, or monohydroxy forms), is exclusively responsible for attenuation of LTB(4) formation. beta-Oxa-21:3n-3 inhibits the conversion of [(3)H]20:4n-6 to [(3)H]5-hydroxyeicosatetraenoic acid and [(3)H]LTB(4) by neutrophils in the presence of calcium ionophore and also suppresses the activity of purified 5-lipoxygenase, but not cyclooxygenase 1 and 2. Beta-oxa-21:3n-3 is taken up by neutrophils and incorporated into phospholipids and neutral lipids. In the presence of calcium ionophore, the leukocytes convert a marginal amount of beta-oxa-21:3n-3 to a 16-monohydroxy-beta-oxa-21:3n-3 derivative. After administration to rodents by gavage or i.p. injection, beta-oxa-21:3n-3 is found to be incorporated into the lipids of various tissues. Thus, beta-oxa-21:3n-3 has the potential to be used in the treatment of inflammatory diseases, which are mediated by products of the lipoxygenase pathway.


Rivellese, A. A. and S. Lilli (2003). "Quality of dietary fatty acids, insulin sensitivity and type 2 diabetes." Biomed Pharmacother 57(2): 84-7.

            Epidemiological evidence and intervention studies clearly indicate that the quality of dietary fat influences insulin sensitivity in humans, in particular, saturated fat worsens it, while monounsaturated and omega-6 polyunsaturated fats improve it. Long chain omega-3 fatty acids do not seem to have any effect on insulin sensitivity, at least in humans. Moreover, there is also good epidemiological evidence that the quality of dietary fat may influence the risk of type 2 diabetes, again with saturated fat increasing and unsaturated fat decreasing this risk. No intervention study is available at the moment on this specific point, even if in the Finnish Diabetes Prevention Study the incidence of type 2 diabetes was reduced by a multifactorial intervention, which also included a reduction of saturated fat intake.


Ristic, V. and G. Ristic (2003). "[Role and importance of dietary polyunsaturated fatty acids in the prevention and therapy of atherosclerosis]." Med Pregl 56(1-2): 50-3.

            INTRODUCTION: Hyperlipoproteinemia is a key factor in development of atherosclerosis, whereas regression of atherosclerosis mostly depends on decreasing the plasma level of total and LDL-cholesterol. Many studies have reported the hypocholesterolemic effect of linolenic acid. TYPES OF POLYUNSATURATED FATTY ACIDS (PUFA): Linoleic and alpha-linolenic acids are essential fatty acids. The main sources of linoleic acid are vegetable seeds and of alpha-linolenic acid-green parts of plants. alpha-linolenic acid is converted to eicosapentaenoic and docosahexaenoic acid. Linoleic acid is converted into arachidonic acid competing with eicosapentaenoic acid in the starting point for synthesis of eicosanoids, which are strong regulators of cell functions and as such, very important in physiology and pathophysiology of cardiovascular system. Eicosanoids derived from eicosapentaneoic acid have different biological properties in regard to those derived from arachidonic acid, i.e. their global effects result in decreased vasoconstriction, platelet aggregation and leukocyte toxicity. ROLE AND SIGNIFICANT OF PUFA: The n-6 to n-3 ratio of polyunsaturated fatty acids in the food is very important, and an optimal ratio 4 to 1 in diet is a major issue. Traditional western diets present absolute or relative deficiency of n-3 polyunsaturated fatty acids, and a ratio 15-20 to 1. In our diet fish and fish oil are sources of eicosapentaenoic and docosahexaenoic acid. Refined and processed vegetable oils change the nature of polyunsaturated fatty acids and obtained derivates have atherogenic properties.


Rissanen, H., P. Knekt, et al. (2003). "Serum fatty acids and breast cancer incidence." Nutr Cancer 45(2): 168-75.

            Fatty acid composition of the diet may be essential to the development of breast cancer. We studied the ability of several fatty acids of serum total lipids to predict breast cancer incidence in a case-control study nested within a longitudinal population study. The proportions of fatty acids in serum total lipids were determined from stored serum samples collected at baseline for 127 incident breast cancer cases and 242 matched controls. Women with a higher proportion of total polyunsaturated fatty acids (PUFAs) in serum had a reduced risk of breast cancer. The odds ratio (OR) between the highest and lowest tertiles of serum PUFA was 0.31 (95% confidence interval, CI = 0.12-0.77). This association was mainly due to n-6 PUFAs and especially to linoleic acid. The ORs were 0.35 (CI = 0.14-0.84) and 0.29 (CI = 0.12-0.73), respectively. Of the monounsaturated fatty acids (MUFAs), higher trans-11-18:1 levels were related to an increased breast cancer risk (OR = 3.69, CI = 1.35-10.06). The association was stronger in postmenopausal than in premenopausal women. The present study suggests that higher serum proportions of the n-6 PUFA linoleic acid and lower proportions of the MUFA trans-11-18:1 fatty acid predict a reduced incidence of breast cancer.


Riddle, T. M., C. J. Fichtenbaum, et al. (2003). "Leptin replacement therapy but not dietary polyunsaturated fatty acid alleviates HIV protease inhibitor-induced dyslipidemia and lipodystrophy in mice." J Acquir Immune Defic Syndr 33(5): 564-70.

            A major complication associated with the use of protease inhibitors (PIs) in treatment of HIV-infected patients is lipid abnormalities including dyslipidemia, lipodystrophy, and liver steatosis. Previous studies revealed that these abnormalities are associated with PI-induced accumulation of activated sterol regulatory element binding proteins (SREBPs) in the nucleus of liver and adipose tissues, resulting in constitutive activation of lipid metabolism genes. This study used the mouse model to determine the potential of polyunsaturated fatty acid (PUFA) diet or leptin replacement therapy to alleviate these PI-induced metabolic abnormalities. Results showed that feeding C57BL/6 mice with a PUFA-rich diet failed to normalize plasma cholesterol and triglyceride levels in ritonavir-treated mice. The PUFA-rich diet also had no effect on ritonavir-induced interscapular fat accumulation and liver steatosis. In contrast, daily administration of leptin significantly reversed the elevated plasma cholesterol level induced by ritonavir. Leptin replacement therapy also significantly reduced the ritonavir-induced interscapular fat mass and improved liver steatosis. Taken together, these data suggest that PI-induced lipid abnormalities, especially dyslipidemia, lipodystrophy, and liver steatosis, may be reduced with leptin replacement therapy.


Richter, W. O. (2003). "Fatty acids and breast cancer--is there a relationship?" Eur J Med Res 8(8): 373-80.

            In 1997 the current database for the relation of polyunsaturated fatty acids in the diet to breast cancer was extensively reviewed by expert committees of the American Institute for Cancer Research and the World Cancer Research Fund. They concluded: "Diets high in polyunsaturated or vegetable fats possibly have no relationship with the risk of breast cancer, independent of any contribution to total fat intake". On the other hand they stated that "Diets high in saturated fat possibly increase the risk of breast cancer" and "Diets high in monounsaturated fat per se possibly have no relationship with the risk of breast cancer, independent of that of total fat." The data in literature clearly confirm these interpretations. No new data exist which have changed the knowledge on the association between intake of fatty acids and breast cancer.


Rhodes, L. E., H. Shahbakhti, et al. (2003). "Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers." Carcinogenesis 24(5): 919-25.

            Dietary omega-3 polyunsaturated fatty acids (omega-3 PUFAs) protect against photocarcinogenesis in animals, but prospective human studies are scarce. The mechanism(s) underlying the photoprotection are uncertain, although omega-3 PUFAs may influence oxidative stress. We examined the effect of supplementation on a range of indicators of ultraviolet radiation (UVR)-induced DNA damage in humans, and assessed effect on basal and post-UVR oxidative status. In a double-blind randomized study, 42 healthy subjects took 4 g daily of purified omega-3 PUFA, eicosapentaenoic acid (EPA), or monounsaturated, oleic acid (OA), for 3 months. EPA was bioavailable; the skin content at 3 months showing an 8-fold rise from baseline, P < 0.01. No consistent pattern of alteration in basal and UVR-exposed skin content of the antioxidants glutathione, vitamins E and C or lipid peroxidation, was seen on supplementation. Sunburn sensitivity was reduced on EPA, the UVR-induced erythemal threshold rising from a mean of 36 (SD 10) mJ/cm(2) at baseline to 49 (16) mJ/cm(2) after supplementation, P < 0.01. Moreover, UVR-induced skin p53 expression, assessed immunohistochemically at 24 h post-UVR exposure, fell from a mean of 16 (SD 5) positive cells/100 epidermal cells at baseline to 8 (4) after EPA supplementation, P < 0.01. Peripheral blood lymphocytes (PBL) sampled on 3 successive days both pre- and post-supplementation, showed no change with respect to basal DNA single-strand breaks or oxidative base modification (8-oxo-dG). However, when susceptibility of PBL to ex vivo UVR was examined using the comet assay, this revealed a reduction in tail moment from 84.4 (SD 3.4) at baseline to 69.4 (3.1) after EPA, P = 0.03. No significant changes were seen in any of the above parameters following OA supplementation. Reduction in this range of early markers, i.e. sunburn, UVR-induced p53 in skin and strand breaks in PBL, indicate protection by dietary EPA against acute UVR-induced genotoxicity; longer-term supplementation might reduce skin cancer in humans.


Rennie, K. L., J. Hughes, et al. (2003). "Nutritional management of rheumatoid arthritis: a review of the evidence." J Hum Nutr Diet 16(2): 97-109.

            Rheumatoid arthritis (RA) is a debilitating disease and is associated with increased risk of cardiovascular disease and osteoporosis. Poor nutrient status in RA patients has been reported and some drug therapies, such as nonsteroidal anti-inflammatory drugs (NSAIDs), prescribed to alleviate RA symptoms, may increase the requirement for some nutrients and reduce their absorption. This paper reviews the scientific evidence for the role of diet and nutrient supplementation in the management of RA, by alleviating symptoms, decreasing progression of the disease or by reducing the reliance on, or combating the side-effects of, NSAIDs. Supplementation with long-chain n-3 polyunsaturated fatty acids (PUFA) consistently demonstrates an improvement in symptoms and a reduction in NSAID usage. Evidence relating to other fatty acids, antioxidants, zinc, iron, folate, other B vitamins, calcium, vitamin D and fluoride are also considered. The present evidence suggests that RA patients should consume a balanced diet rich in long-chain n-3 PUFA and antioxidants. More randomized long-term studies are needed to provide evidence for the benefits of specific nutritional supplementation and to determine optimum intake, particularly for n-3 PUFA and antioxidants.


Reddy, R. D. and J. K. Yao (2003). "Environmental factors and membrane polyunsaturated fatty acids in schizophrenia." Prostaglandins Leukot Essent Fatty Acids 69(6): 385-91.

            There is accumulating evidence of reductions in red blood cell membrane essential fatty acids in patients with schizophrenia. The mechanisms that may underlie these reductions have yet to be determined. It is possible that the observed membrane fatty acid deficits are associated with the development of schizophrenia. Alternatively, the membrane fatty acid deficits may be due to environmental factors, such as smoking and variations in diet, which may not be associated specifically with the pathophysiology of schizophrenia. Patients with schizophrenia smoke cigarettes at very high rates. Cigarette smoke contains many pro-oxidants that contribute directly to oxidative stress. Polyunsaturated fatty acids (PUFAs) are very susceptible to oxidative effects of free radicals. Thus, smoke-induced oxidative stress could plausibly account for reductions in membrane fatty acid in schizophrenia. Recent studies provide conflicting evidence for smoking effects on membrane fatty acid deficits. Likewise, the effects of diet on membrane PUFAs in schizophrenia are not entirely clear. Essential PUFAs need to be consumed in diet. Thus, differences in membrane PUFAs observed between patients and control subjects may be due to dietary variation. Few studies that have examined dietary effects differ in their interpretation of the effects of diet on membrane PUFAs. Thus, the jury is still out whether smoking or dietary effects are the primary causes of membrane PUFA deficits in patients with schizophrenia. Future studies will need to systematically examine the potential effects of smoking and diet, as well as other environmental factors such exercise, to definitively establish whether or not PUFA abnormalities are inherent to schizophrenia.


Raza Shaikh, S., A. C. Dumaual, et al. (2003). "Acyl chain unsaturation in PEs modulates phase separation from lipid raft molecules." Biochem Biophys Res Commun 311(3): 793-6.

            By one hypothesis, phospholipids containing unsaturated fatty acids may be involved in phase separation from the lipid raft molecules sphingomyelin (SM) and cholesterol (CHOL). We tested the effect of increasing the number of double bonds in the acyl chains of phosphatidylethanolamines (PEs) on phase separation from SM/CHOL. The detergent extraction method was employed on various homoacid and heteroacid PEs in mixed vesicles composed of PE/SM/CHOL (1:1:1mol). The disaturated homoacid 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (16:0-16:0PE) showed the least solubility upon detergent extraction whereas maximal solubility was observed for the polyunsaturated homoacid 1,2-didocosahexaenoyl-sn-glycero-3-phosphoethanolamine (22:6-22:6PE). Increasing the number of double bonds in the sn-2 position of heteroacid saturated-unsaturated PEs resulted in an increase in detergent solubility, which correlated with a general decrease in the gel-to-liquid crystalline phase transition temperature of the PEs. Our findings demonstrate that increasing unsaturation in PEs results in increased phase separation from SM/CHOL membranes, which may have implications for cellular signaling.


Rapoport, S. I. (2003). "In vivo approaches to quantifying and imaging brain arachidonic and docosahexaenoic acid metabolism." J Pediatr 143(4 Suppl): S26-34.

            A novel in vivo fatty acid method has been developed to quantify and image brain metabolism of nutritionally essential polyunsaturated fatty acids (PUFAs). In unanesthetized rodents, a radiolabeled PUFA is injected intravenously, and its rate of incorporation into brain phospholipids is determined by chemical analysis or quantitative autoradiography. Results indicate that about 5% of brain arachidonic acid (20:4 n-6) and of docosahexaenoic acid (22:6 n-3) acid are lost daily by metabolism and are replaced from dietary sources through the plasma. Calculated turnover rates of PUFAs in brain phospholipids, due to deesterification by phospholipase A(2) (PLA(2)) followed by reesterification, are very rapid, consistent with active roles of PUFAs in signal transduction and other processes. Turnover rates of arachidonate and docosahexaenoate are independent of each other and probably are regulated by independent sets of enzymes. Brain incorporation of radiolabeled arachidonate can be imaged in response to drugs that bind to receptors coupled to PLA(2) through G proteins, thus measuring PLA(2)-initiated signal transduction. The in vivo fatty method is being extended for human studies using positron emission tomography.


Rao, R. and B. R. Lokesh (2003). "Nutritional evaluation of structured lipid containing omega 6 fatty acid synthesized from coconut oil in rats." Mol Cell Biochem 248(1-2): 25-33.

            Coconut oil is rich in medium chain fatty acids, but deficient in polyunsaturated fatty acids (PUFA). Structured lipids (SL) enriched with omega 6 PUFA were synthesized from coconut oil triglycerides by employing enzymatic acidolysis with free fatty acids obtained from safflower oil. Rats were fed a diet containing coconut oil, coconut oil-safflower oil blend (1:0.7 w/ w) or structured lipid at 10% levels for a period of 60 days. The SL lowered serum cholesterol levels by 10.3 and 10.5% respectively in comparison with those fed coconut oil and blended oil. Similarly the liver cholesterol levels were also decreased by 35.9 and 26.6% respectively in animals fed structured lipids when compared to those fed on coconut oil or the blended oil. Most of the decrease observed in serum cholesterol levels of animals fed structured lipids was found in LDL fraction. The triglyceride levels in serum showed a decrease by 17.5 and 17.4% while in the liver it was reduced by 45.8 and 23.5% in the structured lipids fed animals as compared to those fed coconut oil or blended oil respectively. Differential scanning calorimetric studies indicated that structured lipids had lower melting points and solid fat content when compared to coconut oil or blended oils. These studies indicated that enrichment of coconut oil triglycerides with omega 6 fatty acids lowers its solid fat content. The omega 6 PUFA enriched structured lipids also exhibited hypolipidemic activity.


Ranjekar, P. K., A. Hinge, et al. (2003). "Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients." Psychiatry Res 121(2): 109-22.

            Oxidative stress-mediated cell damage has been considered in the pathophysiology of schizophrenia. Abnormal findings have often been considered related to differences in ethnicity, life style, dietary patterns and medications, all of which influence indices of oxidative stress and oxidative cell damage. To minimize these confounds, schizophrenic patients were compared with age-matched control subjects with the same ethnic background and similar lifestyle, as well as with bipolar mood disorder (BMD) patients. Levels of antioxidant defense enzymes (i.e. superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) were lower in schizophrenic patients than in controls, indicating conditions for increased oxidative stress. The contents of plasma thiobarbituric acid reactive substances (TBARS) were only marginally higher in schizophrenic patients, who had normal levels of arachidonic acid (AA), a major source of TBARS, indicating no significant oxidative membrane lipid peroxidation. Levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), however, were significantly lower in schizophrenic patients. When the same indices in BMD patients were compared with findings in matched controls, levels of only SOD and CAT were lower in the patients, whereas GPx was not. Again, as in schizophrenia, the contents of TBARS were marginally higher in BMD patients with no change in levels of AA. Levels of alpha-linolenic acid and EPA were significantly lower and levels of DHA were slightly lower in BMD patients. These data indicate that certain biochemical characteristics may be common to a spectrum of psychiatric disorders, and suggest supplementation of antioxidants and essential fatty acids might affect clinical outcome.


Ramos, K. L. and A. Colquhoun (2003). "Protective role of glucose-6-phosphate dehydrogenase activity in the metabolic response of C6 rat glioma cells to polyunsaturated fatty acid exposure." Glia 43(2): 149-66.

            Polyunsaturated fatty acids (PUFAs) can influence tumor growth and migration, both in vitro and in vivo. The PUFA gamma-linolenic acid (GLA) has been reported to improve the poor prognosis associated with human gliomas, although its effects at sublethal concentrations on residual cells postsurgery are poorly understood. The study investigated the effects sublethal PUFA doses (90 or 150 microM) may have on rat C6 glioma cell energy metabolism, since an adequate energy supply is essential for cell proliferation, migration, and apoptosis. Of note was the identification of mitochondrial heterogeneity in relation to the mitochondrial membrane potential (MMP), which has been suggested but unproven in previous studies. GLA and eicosapentaenoic acid (EPA) caused significant changes in cellular fatty acid composition and increased the percentage of cells with a low MMP after a 96-h exposure period. The presence of PUFAs inhibited C6 cell proliferation and migration, although apoptosis was not induced. The protein expression and activity of glucose-6-phosphate dehydrogenase was increased after 96-h incubation with 90 microM GLA and EPA and would allow redox regulation through increased NADPH production, permitting the maintenance of adequate intracellular reduced glutathione concentrations and limiting rates of lipid peroxidation and reactive oxygen species generation. Neither NADP(+)-isocitrate dehydrogenase nor NADP(+)-malate dehydrogenase activity responded to PUFAs, suggesting it is glucose-6-phosphate dehydrogenase that is the principal source of NADPH in C6 cells. These data compliment studies showing that higher concentrations of GLA induced glioma cell death and tumor regression and suggest that GLA treatment could be useful for the inhibition of residual cell proliferation and migration after surgical removal of the tumor mass.


Ramadan, M. F., L. W. Kroh, et al. (2003). "Radical scavenging activity of black cumin (Nigella sativa L.), coriander (Coriandrum sativum L.), and niger (Guizotia abyssinica Cass.) crude seed oils and oil fractions." J Agric Food Chem 51(24): 6961-9.

            Crude vegetable oils are usually oxidatively more stable than the corresponding refined oils. Tocopherols, phospholipids (PL), phytosterols, and phenols are the most important natural antioxidants in crude oils. Processing of vegetable oils, moreover, could induce the formation of antioxidants. Black cumin (Nigella sativa L.), coriander (Coriandrum sativum L.), and niger (Guizotia abyssinica Cass.) crude seed oils were extracted with n-hexane and the oils were further fractionated into neutral lipids (NL), glycolipids (GL), and PL. Crude oils and their fractions were investigated for their radical scavenging activity (RSA) toward the stable galvinoxyl radical by electron spin resonance (ESR) spectrometry and toward 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical by spectrophotometric method. Coriander seed oil and its fractions exhibited the strongest RSA compared to black cumin and niger seed oils. The data correlated well with the total content of polyunsaturated fatty acids, unsaponifiables, and PL, as well as the initial peroxide values of crude oils. In overall ranking, RSA of oil fractions showed similar patterns wherein the PL exhibited greater activity to scavenge both free radicals followed by GL and NL, respectively. The positive relationship observed between the RSA of crude oils and their color intensity suggests the Maillard reaction products may have contributed to the RSA of seed oils and their polar fractions. The results demonstrate the importance of minor components in crude seed oils on their oxidative stability, which will reflect on their food value and shelf life. As part of the effort to assess the potential of these seed oils, the information is also of importance in processing and utilizing the crude oils and their byproducts.


Rallidis, L. S., G. Paschos, et al. (2003). "Dietary alpha-linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients." Atherosclerosis 167(2): 237-42.

            BACKGROUND: Inflammation plays an important role in the pathogenesis of coronary artery disease. We examined whether dietary supplementation with alpha-linolenic acid (ALA, 18:3n-3) affects the levels of inflammatory markers in dyslipidaemic patients. METHODS: We recruited 76 male dyslipidaemic patients (mean age=51+/-8 years) following a typical Greek diet. They were randomly assigned either to 15 ml of linseed oil (rich in ALA) per day (n=50) or to 15 ml of safflower oil (rich in linoleic acid (LA, 18:2n-6)) per day (n=26). The ratio of n-6:n-3 in linseed oil supplemented group was 1.3:1 and in safflower oil supplemented group 13.2:1. Dietary intervention lasted for 3 months. Blood lipids and C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) levels were determined prior and after intervention. CRP and SAA were measured by nephelometry and IL-6 by immunoassay. RESULTS: Dietary supplementation with ALA decreased significantly CRP, SAA and IL-6 levels. The median decrease of CRP was 38% (1.24 vs. 0.93 mg/l, P=0.0008), of SAA 23.1% (3.24 vs. 2.39 mg/l, P=0.0001) and of IL-6 10.5% (2.18 vs. 1.7 pg/ml, P=0.01). The decrease of inflammatory markers was independent of lipid changes. Dietary supplementation with LA did not affect significantly CRP, SAA and IL-6 concentrations but decreased cholesterol levels. CONCLUSIONS: Dietary supplementation with ALA for 3 months decreases significantly CRP, SAA and IL-6 levels in dyslipidaemic patients. This anti-inflammatory effect may provide a possible additional mechanism for the beneficial effect of plant n-3 polyunsaturated fatty acids in primary and secondary prevention of coronary artery disease.


Quiles, J. L., J. R. Huertas, et al. (2003). "Dietary fat (virgin olive oil or sunflower oil) and physical training interactions on blood lipids in the rat." Nutrition 19(4): 363-8.

            OBJECTIVE: We investigated whether the intake of virgin olive oil or sunflower oil and performance of physical exercise (at different states) affect plasma levels of triacylglycerols, total cholesterol, and fatty acid profile in rats. METHODS: The study was carried out with six groups of male rats subjected for 8 wk to a diet based on virgin olive oil (three groups) or sunflower oil (three groups) as dietary fat. One group for each diet acted as sedentary control; the other two groups ran in a treadmill for 8 wk at 65% of the maximum oxygen consumption. One group for each diet was killed 24 h after the last bout of exercise and the other was killed immediately after the exercise performance. Triacylglycerols, total cholesterol, and fatty acid profile were analyzed in plasma. Analysis of variance was used to test differences among groups. RESULTS: Animals fed on virgin olive oil had lower triacylglycerol and cholesterol values. Physical exercise reduced these parameters with both dietary treatments. Fatty acid profile showed higher monounsaturated fatty acid proportion in virgin olive fed oil animals and a higher omega-6 polyunsaturated fatty acid proportion in sunflower oil fed animals. Physical exercise reduced the levels of monounsaturated fatty acids with both diets and increased the proportions of omega-3 polyunsaturated fatty acids. CONCLUSIONS: Results from the present study supported the idea that physical exercise and the intake of virgin olive oil are very good ways of reducing plasma triacylglycerols and cholesterol, which is desirable in many pathologic situations. Concerning findings on fatty acid profile, we had results similar to those of other investigators regarding the effect of different sources of dietary fat on plasma. The most interesting results came from the effect of physical exercise, with significant increases in the levels of omega-3 polyunsaturated fatty acids, which may contribute to the antithrombotic state and lower production of proinflammatory prostanoids attributed to physical exercise.


Qian, S. Y., G. H. Yue, et al. (2003). "Identification of all classes of spin-trapped carbon-centered radicals in soybean lipoxygenase-dependent lipid peroxidations of omega-6 polyunsaturated fatty acids via LC/ESR, LC/MS, and tandem MS." Free Radic Biol Med 34(8): 1017-28.

            Using the combined techniques of on-line high performance liquid chromatography/electron spin resonance (LC/ESR) and mass spectrometry (MS), we previously identified spin-trapped adducts of all expected carbon-centered lipid-derived radicals ((*)L(d)) formed in linoleic acid peroxidation. In the present study, spin trapped lipid-derived carbon-centered radicals formed from the reactions of two omega-6 polyunsaturated fatty acids (PUFAs: linoleic and arachidonic acids) with soybean lipoxygenase in the presence of alpha-[4-pyridyl 1-oxide]-N-tert-butyl nitrone (POBN) were identified using a combination of LC/ESR and LC/MS. All expected lipid-derived carbon-centered radicals in lipoxygenase-dependent peroxidations of linoleic acid and arachidonic acid were detected and identified by the combination of LC/ESR and LC/MS with confirmation by tandem mass spectrometry (MS/MS). The five classes of (*)L(d) formed from both omega-6 PUFAs including lipid alkyl radicals (L(*)), epoxyallyic radicals (OL(*)), dihydroxyallyic radicals ((*)L(OH)(2)), and a variety of R(*) and (*)RCOOH from beta-scission of lipid alkoxyl radicals, gave distinct retention times: POBN/(*)L(OH)(2) approximately 4-6 min, POBN/R(*) and POBN/(*)RCOOH approximately 8-22 min, POBN/L(*) and PBON/OL(*) approximately 25-36 min. The major beta-scission products in peroxidations of omega-6 PUFAs were the pentyl radicals. The ratio of beta-scission products, however, varied significantly depending on pH, [PUFA], as well as [O(2)].


Qian, S. Y., Q. Guo, et al. (2003). "Identification of spin trapped carbon-centered radicals in soybean lipoxygenase-dependent peroxidations of omega-3 polyunsaturated fatty acids by LC/ESR, LC/MS, and tandem MS." Free Radic Biol Med 35(1): 33-44.

            With the combined techniques of on-line liquid chromatography/electron spin resonance (LC/ESR) and on-line liquid chromatography/mass spectrometry (LC/MS), we have previously characterized all classes of lipid-derived carbon-centered radicals (*Ld) formed from omega-6 polyunsaturated fatty acids (PUFAs: linoleic acid and arachidonic acid). In the present study, the carbon-centered radicals formed from two omega-3 PUFAs (linolenic acid and docosahexaenoic acid) resulting from their reactions with soybean lipoxygenase in the presence of alpha-[4-pyridyl 1-oxide]-N-tert-butylnitrone (POBN) were investigated using the combination of LC/ESR and LC/MS techniques. A total of 16 POBN trapped carbon-centered radicals formed from the peroxidation of linolenic acid and 11 formed from the peroxidation of docosahexaenoic acid were detected by LC/ESR, identified by LC/MS, and structurally confirmed by tandem mass analysis (MS/MS). The on-line ESR chromatograms and MS chromatograms obtained from two omega-3 PUFAs closely resembled each other not only because the four major beta-scission products, including an ethyl radical and three isomeric pentenyl radicals, were formed from each PUFA, but also because isomeric POBN adducts of lipid dihydroxyallylic radicals from both PUFAs had almost identical chromatographic retention times.


Qi, Q., Y. F. Huang, et al. (2003). "Molecular and biochemical characterization of an aminoalcoholphosphotransferase (AAPT1) from Brassica napus: effects of low temperature and abscisic acid treatments on AAPT expression in Arabidopsis plants and effects of over-expression of BnAAPT1 in transgenic Arabidopsis." Planta 217(4): 547-58.

            Aminoalcoholphosphotransferases (AAPT, EC and EC catalyze the transfer of CDP-aminoalcohols to sn-1, 2 diacylglycerol (DAG) to form phosphatidylaminoalcohols with the release of CMP. The Brassica napus L. AAPT1 gene (designated BnAAPT1) was identified from cDNA libraries of seedlings and developing seeds. Functional characterization was accomplished by heterologous expression of BnAAPT1 in a yeast strain deficient in AAPT activities. BnAAPT1 exhibited a greater preference for utilizing CDP-choline as a substrate with Vmax of 35 [14C]phosphatidylcholine nmol h(-1) mg(-1) protein and apparent Km of 32 microM while CDP-ethanolamine had a Vmax of 13 [14C]phosphatidylethanolamine nmol h(-1) mg(-1)protein and an apparent Km of 127 microM. The enzyme was activated by Mg2+, Mn2+ and phospholipid mixtures, and inhibited by Ca2+. A CDP-alcohol phosphotransferase motif, Asp99-Gly100-(X2)-Ala103-Arg104-(X8)-Gly113-(X3)-Asp117-(X3)-Asp121, was completely conserved in BnAAPT1 and its catalytic role was confirmed by scanning alanine mutagenesis. Over-expression of BnAAPT1 under the control of the double 35S promoter in transgenic Arabidopsis thaliana (L.) Heynh. plants led to elevated levels of the corresponding transcript and enzyme activity. In four of the high over-expression transgenic lines, phospholipid and fatty acid composition analyses revealed that chloroplastidic and extrachloroplastidic membranes isolated from transgenic leaves had about a 25% increase in phosphatidylcholine and in the proportions of polyunsaturated fatty acids [18:2+18:3], relative to the control. There were also consistent, but small differences observed in the proportions of 18:3 in transgenic green siliques and in 20:1 in mature transgenic seeds of these lines. Induction of Arabidopsis AAPT transcription in response to (+)-abscisic acid and low-temperature treatments, and the cold tolerance in BnAAPT1 transgenic seedlings implies that AAPT may play a role in resistance to damage at low growth temperatures.


Qi, B., T. C. Fraser, et al. (2003). "The variant 'his-box' of the C18-Delta9-PUFA-specific elongase IgASE1 from Isochrysis galbana is essential for optimum enzyme activity." FEBS Lett 547(1-3): 137-9.

            IgASE1, a C18-Delta9-polyunsaturated fatty acid-specific fatty acid elongase component from Isochrysis galbana, contains a variant histidine box (his-box) with glutamine replacing the first histidine of the conserved histidine-rich motif present in all other known equivalent proteins. The importance of glutamine and other variant amino acid residues in the his-box of IgASE1 was determined by site-directed mutagenesis. Results showed that all the variation in amino acid sequence between this motif in IgASE1 and the consensus sequences of other elongase components was required for optimum enzyme activity. The substrate specificity was shown to be unaffected by these changes suggesting that components of the his-box are not directly responsible for substrate specificity.


Puskas, L. G., K. Kitajka, et al. (2003). "Short-term administration of omega 3 fatty acids from fish oil results in increased transthyretin transcription in old rat hippocampus." Proc Natl Acad Sci U S A 100(4): 1580-5.

            Reduced brain levels of long chain polyunsaturated fatty acids [arachidonic acid and docosahexanoic acid (DHA)] are observed in elderly subjects and patients with Alzheimer's disease. To determine the effects of n-3 fatty acids on aged rat brain, 2-year-old rats were fed fish oil (27% DHA content) for 1 month, and gene expression analysis and fatty acid and molecular species composition of the major phospholipid species were assessed. No significant alteration could be observed in the fatty acid composition of ethanolamine phosphoglycerides and phosphatidylserines with the exception of DHA, which was slightly higher in brains of rats receiving fish oil. However, a drastic reduction in arachidonic acid in phosphatidylinositoles was observed. The expression of 23 genes was altered in response to fish oil feeding in the hippocampus. The transcription of transthyretin (TTR) was induced by 10-fold as evidenced by microarray analysis and confirmed by real-time quantitative RT-PCR. Expression of IL-1 and NO synthase, which has been implicated in the prevention of neurological diseases, was unaltered. TTR is an amyloid beta protein scavenger, so an increase in its expression could prevent amyloid aggregate formation. We believe the beneficial effects of fish oil might be common to other agents, i.e., induce TTR expression, like nicotine and Ginkgo biloba extract.


Puertollano, M. A., M. A. de Pablo, et al. (2003). "Anti-oxidant properties of N-acetyl-L-cysteine do not improve the immune resistance of mice fed dietary lipids to Listeria monocytogenes infection." Clin Nutr 22(3): 313-9.

            BACKGROUND & AIMS: Current knowledge of the potential effects that several dietary lipids exert on immune functions indicates that these substances participate actively in the modulation of immune system by which they contribute to the improvement of the conditions of patients suffering from inflammatory disorders. However, long-chain n-3 polyunsaturated fatty acids induce an immunosuppressive status that leads to a reduction of the host natural resistance to infectious agents as well as to an enhancement of oxidative damage. Hence, the present study has been designed to evaluate the effects on the immune system of the antioxidant N-acetyl-L-cysteine (NAC) in mice fed dietary lipids and infected with Listeria monocytogenes. METHODS: Balb/c mice were fed for 4 weeks with diets containing either olive oil (OO, 20% by weight), fish oil (FO, 20% by weight) or hydrogenated coconut oil (HCO, 20% by weight). After dietary lipid administration mice were experimentally infected with L. monocytogenes or treated with NAC (25mg/ml intraperitoneally). RESULTS: NAC at a concentration of 1mM promoted a loss of cell viability, although no differences were observed among the four groups. After injection of NAC in combination with L. monocytogenes, 25% of mice fed a low-fat (LF) diet survived. However, in the groups fed dietary lipids no effect on survival of mice was found. NAC participated in the reduction of superoxide anion generation measured with nitroblue tetrazolium (NBT) in the group fed a FO diet. Finally, NAC reduced the recovery of L. monocytogenes from spleen of mice fed diets containing LF or HCO. CONCLUSIONS: On the basis of these results, we can confirm that the administration of NAC improves survival in mice fed LF diet, whereas a reduction in the generation of superoxide radicals was measured in mice fed a FO diet and infected with L. monocytogenes. Similarly, bacterial recovery was diminished in mice fed diets containing LF or HCO. Hence, these data reveal a beneficial effect of NAC in mice fed LF or HCO and a detrimental action of this antioxidant in mice fed diets containing FO or OO.


Puertollano, M. A., M. A. de Pablo, et al. (2003). "Polyunsaturated fatty acids induce cell death in YAC-1 lymphoma by a caspase-3-independent mechanism." Anticancer Res 23(5A): 3905-10.

            BACKGROUND: The involvement of certain fatty acids in the induction of apoptosis has been established recently. In fact, considerable attention has been given in the past few years to the participation of polyunsaturated fatty acids as substances capable of modulating tumor cell growth. MATERIALS AND METHODS: Fatty acids such as eicosapentaenoic acid (EPA), linolenic acid (LNA), arachidonic acid (AA), linoleic acid (LA), oleic acid (OA) or stearic acid (SA) were added to YAC-1 tumor cells. RESULTS: Incubation of cells with fatty acids revealed a loss of cell viability in a dose-dependent manner. Quantification of DNA fragmentation showed a significant increase particularly in cells treated in the presence of LA, whereas the accumulation of triacylglycerols in the form of cytoplasmic lipid droplets was significantly enhanced in cells cultured with EPA, LNA or AA. The production of reactive oxygen species (ROS) was substantially increased after cell incubation. Nevertheless, the analysis of caspase-3 activity indicated a relevant increase in cells cultured in the presence of LA, OA or SA, but not in cells cultured with EPA, LNA or AA. CONCLUSION: On the basis of these results, we can speculate that long-chain polyunsaturated fatty acids such as EPA and AA as well as LNA induce cell death in YAC-1 lymphoma by an independent mechanism of caspase-3 activation.


Probst-Hensch, N. M., H. Wang, et al. (2003). "Determinants of circulating insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations in a cohort of Singapore men and women." Cancer Epidemiol Biomarkers Prev 12(8): 739-46.

            Variation in the circulating concentrations of the insulin-like growth factor (IGF) system has been implicated in the etiology of chronic diseases including cancer (prostate, breast, colon, and lung), heart disease, type 2 diabetes, and osteoporosis. We searched for sociodemographic, anthropometric, reproductive, lifestyle, and dietary determinants of IGF-I and insulin-like growth factor binding protein (IGFBP) -3 serum concentrations. Serum samples were collected in a Singapore Chinese cohort with a mean age of 61 years. Subject information was assessed during an in-person interview. Radioimmunometrically measured IGF-I and IGFBP-3 concentrations were available for 312 men and 326 postmenopausal women ages 50 years or older. Mean IGF-I concentrations were 144 ng/ml and 121 ng/ml for men and women, respectively (gender difference, P < 0.0001), and mean IGFBP-3 concentrations were 3710 ng/ml and 4147 ng/ml for men and women, respectively (gender difference, P < 0.0001). IGF-I and IGFBP-3 decreased with age (P for trend <0.0001); the age-related decrease in the IGF-I:IGFBP-3 molar ratio was stronger in women than men. IGF-I concentrations were higher among physically inactive subjects and among women with an early age at menarche. Consumption of saturated fat was found to decrease, and intake of omega-3 polyunsaturated fatty acids and of dietary fiber was found to increase circulating IGFBP-3 concentrations. Intake of calcium from food and supplement was associated positively with circulating IGF-I, IGFBP-3, and molar ratio. Intake of soy was associated positively with IGF-I and molar ratio concentrations, but only in men. The results of this study lend additional support to the hypothesis that circulating IGF-I concentrations increase the risk of prostate, bladder, colorectal, and breast cancer.


Portero-Otin, M., M. J. Bellmunt, et al. (2003). "Protein modification by advanced Maillard adducts can be modulated by dietary polyunsaturated fatty acids." Biochem Soc Trans 31(Pt 6): 1403-5.

            Advanced Maillard adducts, such as N epsilon-(carboxymethyl)lysine and N epsilon-(carboxyethyl)lysine, can be formed efficiently in vitro from both peroxidation of polyunsaturated fatty acids and glycolysis intermediates. In an attempt to differentiate the in vivo influence of the two pathways in these modifications, Wistar rats were chronically fed with specially designed diets rich in saturated or unsaturated fats. The degree of fatty acid unsaturation of all analysed organs (liver, kidney, brain) was altered by these dietary stresses. Protein glycoxidative and lipoxidative modifications were measured by GC/MS. In accordance with fatty acid profiles, concentrations of N epsilon-(malondialdehyde)lysine in these tissues were significantly increased in animals fed the unsaturated fat diet. In contrast, N epsilon-(carboxymethyl)lysine and N epsilon-(carboxyethyl)lysine concentrations were strongly dependent on the tissue analysed; although the unsaturated fat diet increased their levels significantly in brain, levels were unchanged in kidney and decreased in liver. These later results could be interpreted on the basis that polyunsaturated fatty acids decrease the expression of several glycolytic enzymes in liver. Globally, these data suggest that tissue-specific metabolic characteristics play a key role in the degree of cellular protein modification by Maillard reactions, e.g. by modulation of the concentration of glycolysis intermediates or via specific defensive systems in these organs.


Porsgaard, T., E. M. Straarup, et al. (2003). "Gastric emptying in rats following administration of a range of different fats measured as acetaminophen concentration in plasma." Ann Nutr Metab 47(3-4): 132-8.

            AIM: To investigate the gastric emptying upon administration of ten different fats in order to determine whether major differences in fatty acid profiles resulted in differences in gastric emptying. METHODS: Gastric emptying was measured as the appearance of acetaminophen in plasma which represents an indirect measure of gastric emptying. Emulsified fats with added acetaminophen were fed by gavage to rats, and the plasma concentration of acetaminophen was followed for 3 h by repeated blood sampling from the carotid artery. The fats administered included rapeseed, corn, and fish oils, lard, and cocoa butter as well as different structured lipids containing decanoic acid (10:0) and long-chain n-3 polyunsaturated fatty acids of marine origin. Overall, these fats had wide variations in fatty acid compositions and triacylglycerol structures. RESULTS: No statistically significant differences were observed in gastric emptying between the groups fed the different fats, except for the emptying of tridecanoin (tri-10:0) that was statistically significantly slower than that of randomized oil, cocoa butter, and rapeseed oil (p < 0.05). The slower emptying of tri-10:0 could be caused by a lower caloric intake of this fat as compared with the other fats, because similar weights of fat were administered. CONCLUSION: The gastric emptying of fat was not influenced by fatty acid composition and triacylglycerol structure of the fats administered.


Pischon, T., S. E. Hankinson, et al. (2003). "Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women." Circulation 108(2): 155-60.

            BACKGROUND: Polyunsaturated fatty acid intake favorably affects chronic inflammatory-related diseases such as cardiovascular disease; however, high intake of n-6 fatty acids may attenuate the known beneficial effects of n-3 fatty acids. METHODS AND RESULTS: We investigated habitual dietary n-3 fatty acid intake and its interaction with n-6 fatty acids in relation to the plasma inflammatory markers C-reactive protein, interleukin 6, and soluble tumor necrosis factor receptors 1 and 2 (sTNF-R1 and R2) among 405 healthy men and 454 healthy women. After adjustment for other predictors of inflammation, intake of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was inversely associated with plasma levels of sTNF-R1 and sTNF-R2 (P=0.03 and P<0.001, respectively) and somewhat less so for C-reactive protein (P=0.08). n-3 alpha-linolenic acid and n-6 cis-linoleic acid were not significantly related to the inflammatory markers. We found little if any association between n-3 fatty acid (EPA+DHA) intake and tumor necrosis factor receptors among participants with low intake of n-6 but a strong inverse association among those with high n-6 intake (P=0.04 and 0.002 for interaction of n-3 with n-6 on sTNF-R1 and sTNF-R2, respectively). CONCLUSIONS: These results suggest that n-6 fatty acids do not inhibit the antiinflammatory effects of n-3 fatty acids and that the combination of both types of fatty acids is associated with the lowest levels of inflammation. The inhibition of inflammatory cytokines may be one possible mechanism for the observed beneficial effects of these fatty acids on chronic inflammatory-related diseases.


Pironi, L., M. Guidetti, et al. (2003). "Peroxidation potential of lipid emulsions after compounding in all-in-one solutions." Nutrition 19(9): 784-8.

            OBJECTIVES: We investigated the peroxidation potential of fat emulsions in all-in-one solutions (AIOs). METHODS: Three 20% emulsions were compared: soybean oil (SO; 60% polyunsaturated fatty acids [PUFAs], alpha-tocopherol:PUFAs = 0.44), soybean plus medium-chain triacylglycerol (SO-MCT; 31% PUFAs, alpha-tocopherol:PUFAs = 0.35), and olive oil (OO; 21% PUFAs, alpha-tocopherol:PUFAs = 1.42). For each emulsion, six AIO solutions were prepared by adding 250 mL of emulsion to a lipid-free solution. Lipid peroxide (LPX) and malondialdehyde (MDA) concentrations were evaluated in fat emulsions, lipid-free solutions, and AIOs immediately (T0) and 24 h (T24) after lipid addition. Statistical analysis was done with analysis of variance. RESULTS: Fat emulsion LPX in SO-MCT was lower than that in SO (P = 0.015) and OO (P = 0.024); LPX in SO was greater than that in OO (P = 0.013); MDA in SO was greater than that in SO-MCT (P = 0.001) and OO (P = 0.013); and MDA in SO-MCT was greater than that in OO (P = 0.001). In comparison with MDA at AIO-T0, MDA at AIO-T24 increased in SO (P = 0.005) and SO-MCT (P < 0.001) and decreased in OO (P = 0.003); at AIO-T24, LPX was greater in SO, but not significantly. CONCLUSIONS: In AIO bags, LPX occurred within 24 h after the addition of the lipid emulsion and seemed to be directly related to the PUFA content and inversely related to the alpha-tocopherol:PUFA ratio of the emulsion.


Piolot, A., D. Blache, et al. (2003). "Effect of fish oil on LDL oxidation and plasma homocysteine concentrations in health." J Lab Clin Med 141(1): 41-9.

            Oxidation of low-density lipoprotein (LDL) and hyperhomocysteinemia are believed to play a role in therogenesis. Whether n-3 polyunsaturated fatty acids increase LDL susceptibility to oxidation or influence homocysteine (Hcy) metabolism has long been a subject of controversy. In this study, we evaluated the effect of 8 weeks of dietary supplementation with 6 g/day of fish oil (FO; 3 g of n-3 fatty acids) on plasma lipoproteins, in vitro LDL peroxidation, antioxidant status, and plasma Hcy concentrations in 16 normolipidemic subjects. FO rapidly and significantly (P < .01) decreased plasma total and very low density lipoprotein triglyceride concentrations and had no effect on LDL or high-density-lipoprotein cholesterol. The mean lag time before onset of Cu(2+)-induced LDL oxidation, as well as plasma and LDL alpha-tocopherol and beta-carotene concentrations, was unchanged. However, changes in plasma aminothiol concentrations occurred during the study. Specifically, a progressive and significant increase in total Hcy plasma concentrations was observed (13.4% and 20% after 4 and 8 weeks, respectively; P < .01). Total glutathione concentrations were significantly higher after 8 weeks (P < .05). The tHcy increase was not associated with changes in plasma folate or vitamin B(12) concentrations. However, concentrations of plasma nitric oxide metabolites (NO(x) = NO(2) + NO(3)) were significantly higher than at baseline after 8 weeks of FO intake (74%; P < .01). Further, the changes in total Hcy and NO(x) plasma concentrations observed after 8 weeks of FO were found to be significantly correlated (r = .78, P < .001). With this study, we report for the first time the apparent interaction of n-3 fatty acids and nitric oxide on Hcy metabolism.


Pilitsis, J. G., W. M. Coplin, et al. (2003). "Free fatty acids in cerebrospinal fluids from patients with traumatic brain injury." Neurosci Lett 349(2): 136-8.

            Free fatty acid (FFA) concentrations in cerebrospinal fluid (CSF) are recognized as markers of brain damage in animal studies. There is, however, relatively little information regarding FFA concentrations in human CSF in normal and pathological conditions. The present study examined FFA concentrations in CSF from 15 patients with traumatic brain injury (TBI) and compared the data with values obtained from 73 contemporary controls. Concentrations of specific FFAs from TBI patients, obtained within 48 h of the insult were significantly greater than those in the control group (arachidonic, docosahexaenoic and myristic, P<0.001; oleic, palmitic, P<0.01; linoleic, P<0.05). Higher concentrations of total polyunsaturated fatty acids (P<0.001) and of arachidonic, myristic and palmitic acids measured individually in CSF (P<0.01) obtained 1 week after the insult were associated with a worse outcome at the time of hospital discharge using the Glasgow Outcome Scale. This preliminary investigation suggests that CSF FFA concentrations may be useful as a predictive marker of outcome following TBI.


Pilitsis, J. G., W. M. Coplin, et al. (2003). "Measurement of free fatty acids in cerebrospinal fluid from patients with hemorrhagic and ischemic stroke." Brain Res 985(2): 198-201.

            Free fatty acid (FFA) concentrations in cerebrospinal fluid (CSF) from patients with ischemic and hemorrhagic stroke (n=25) and in contemporary controls (n=73) were examined using HPLC. Concentrations of CSF FFAs from ischemic and hemorrhagic stroke patients obtained within 48 h of the insult were significantly greater than in control patients. Higher concentrations of polyunsaturated fatty acids (PUFAs) in CSF obtained within 48 h of insult were associated with significantly lower (P<0.05) admission Glasgow Coma Scale scores and worse outcome at the time of hospital discharge, using the Glasgow Outcome Scale (P<0.01).


Piers, L. S., K. Z. Walker, et al. (2003). "Substitution of saturated with monounsaturated fat in a 4-week diet affects body weight and composition of overweight and obese men." Br J Nutr 90(3): 717-27.

            A randomised crossover study of eight overweight or obese men (aged 24-49 years, BMI 25.5-31.3 kg/m(2)), who followed two diets for 4 weeks each, was performed to determine whether substitution of saturated fat with monounsaturated fat affects body weight and composition. Subjects were provided with all food and beverages as modules (selected ad libitum) of constant macronutrient composition, but differing energy content. The % total energy from saturated fat, monounsaturated fat and polyunsaturated fat was 24, 13 and 3 % respectively on the saturated fatty acid (SFA)-rich diet and 11, 22 and 7 % respectively on the monounsaturated fatty acid (MUFA)-rich diet. MUFA accounted for about 80 % of the unsaturated fats consumed on both diets. Body composition, blood pressure, energy expenditure (resting and postprandial metabolic rates, substrate oxidation rate, physical activity), serum lipids, the fatty acid profile of serum cholesteryl esters and plasma glucose and insulin concentrations were measured before and after each diet period. Significant (P< or =0.05) differences in total cholesterol and the fatty acid composition of serum cholesteryl esters provided evidence of dietary adherence. The men had a lower weight (-2.1 (SE 0.4) kg, P=0.0015) and fat mass (-2.6 (SE 0.6) kg, P=0.0034) at the end of the MUFA-rich diet as compared with values at the end of the SFA-rich diet. No significant differences were detected in energy or fat intake, energy expenditure, substrate oxidation rates or self-reported physical activity. Substituting dietary saturated with unsaturated fat, predominantly MUFA, can induce a small but significant loss of body weight and fat mass without a significant change in total energy or fat intake.


Phillips, M., R. N. Cataneo, et al. (2003). "Volatile markers of breast cancer in the breath." Breast J 9(3): 184-91.

            Breast cancer is accompanied by increased oxidative stress and induction of polymorphic cytochrome P-450 mixed oxidase enzymes (CYP). Both processes affect the abundance of volatile organic compounds (VOCs) in the breath because oxidative stress causes lipid peroxidation of polyunsaturated fatty acids in membranes, producing alkanes and methylalkanes which are catabolized by CYP. We performed a pilot study of breath VOCs, a potential new marker of disease in women with breast cancer. This was a combined case-control and cross-sectional study of women with abnormal mammograms scheduled for a breast biopsy. Breath samples were analyzed by gas chromatography and mass spectroscopy in order to determine the breath methylated alkane contour (BMAC), a three-dimensional display of the alveolar gradients (abundance in breath minus abundance in room air) of C4-C20 alkanes and monomethylated alkanes. BMACs in women with and without breast cancer were compared using forward stepwise discriminant analysis. Two hundred one breath samples were obtained from women with abnormal mammograms and biopsies read by two pathologists. There were 51 cases of breast cancer in 198 concordant biopsies. The breath test distinguished between women with breast cancer and healthy volunteers with a sensitivity of 94.1% (48/51) and a specificity of 73.8% (31/42) (cross-validated sensitivity 88.2% (45/51), specificity 73.8% (31/42)). Compared to women with abnormal mammograms and no cancer on biopsy, the breath test identified breast cancer with a sensitivity of 62.7% (32/51) and a specificity of 84.0% (42/50) (cross-validated sensitivity of 60.8% (31/51), specificity of 82.0% (41/50)). The negative predictive value (NPV) of a screening breath test for breast cancer was superior to a screening mammogram (99.93% versus 99.89%); the positive predictive value (PPV) of a screening mammogram was superior to a screening breath test (4.63% versus 1.29%). A breath test for markers of oxidative stress accurately identified women with breast cancer, with an NPV superior to a screening mammogram. This breath test could potentially be employed as a primary screen for breast cancer. Confirmatory studies in larger groups are required.


Petit, H. V. (2003). "Digestion, milk production, milk composition, and blood composition of dairy cows fed formaldehyde treated flaxseed or sunflower seed." J Dairy Sci 86(8): 2637-46.

            Forty midlactation Holstein cows averaging 635 kg of body weight (SE = 8) were allotted at wk 25 of lactation to ten groups of four cows blocked for similar calving dates to determine the effects of formaldehyde treatment of flaxseed and sunflower seed on fatty acid composition of blood and milk, milk yield, feed intake, and apparent digestibility. Cows were fed a total mixed diet based on grass silage and supplements for ad libitum intake over a 10-wk period. Cows within each block were assigned to one of the four isonitrogenous supplements based on either untreated whole flaxseed, formaldehyde-treated whole flaxseed, untreated whole sunflower seed, or formaldehyde-treated whole sunflower seed. Cows fed whole flaxseed compared with sunflower seed maintained greater dry matter (DM) intake (20.3 vs. 18.9 kg/d). Intake of DM, expressed as a percentage of body weight, was increased by adding formaldehyde to oilseeds (3.24 vs. 2.98%). Milk production was similar for cows fed flaxseed and those fed sunflower. Formaldehyde treatment of flaxseed and sunflower seed increased milk production by an average of 2.65 kg/d. Efficiency of fat-corrected milk yield per kilogram of DM intake was increased by formaldehyde treatment (1.31 vs. 1.21), and it was greater with sunflower seed than with flaxseed (1.33 vs.1.21). Protein concentration in milk was greater for cows fed flaxseed (3.38%) compared with those fed sunflower seed (3.21%) and formaldehyde had no effect. Apparent digestibility of DM was not affected by type of seed but it was greater for cows fed formaldehyde-treated seeds. Cows fed formaldehyde-treated flaxseed had the greatest apparent digestibilities of acid detergent and neutral detergent fiber compared with those fed the other diets. Apparent digestibilities of fatty acids were greater for sunflower seed than for flaxseed-based diets. In general, formaldehyde treatment had limited effect on milk fatty acid composition, suggesting that formaldehyde was not very effective in protecting polyunsaturated fatty acids against ruminal biohydrogenation. Feeding flaxseed resulted in the lowest omega 6 to omega 3 fatty acid ratio. The data suggest that both flaxseed and sunflower seed are acceptable fat sources for midlactating cows and that flaxseed increases milk protein percentage compared to sunflower seed.


Peroval, C., F. Debeaufort, et al. (2003). "Modified arabinoxylan-based films. Part B. Grafting of omega-3 fatty acids by oxygen plasma and electron beam irradiation." J Agric Food Chem 51(10): 3120-6.

            Arabinoxylans (AXs) are byproducts of the cereal milling industry. To obtain high-value products, AXs have been used as a film-forming agent. Hence, AX-based films are poor water vapor barriers. The objectives of this study were to graft omega-3 (omega3) fatty acids onto AX polymeric chains by using two new technologies: cold plasma and electron beam (EB) irradiation. Results show that the surface hydrophobicity of the modified films is higher than that of a waxy coating or a low-density polyethylene (LDPE) film. In addition, FTIR spectroscopy analysis reveals vibration bands attributed to new chemical functions. Finally, a decrease in water vapor permeability (WVP) is obtained for the film treated with the alpha-linolenic acid-rich oil. This result could be explained by a better diffusion of this shorter polyunsaturated fatty acid into the AX network. Linseed oils provide better barrier properties and a higher surface hydrophobicity than oils extract from marine oils. Edible oils were chosen for edible application of these films to retard moisture transfers in stuffed biscuits.


Perez, C., J. R. Canal, et al. (2003). "Experimental diabetes treated with ficus carica extract: effect on oxidative stress parameters." Acta Diabetol 40(1): 3-8.

            Parameters related to oxidative stress were studied in rats divided into 4 groups: streptozotocin-induced diabetic rats (n=10), diabetic rats who received a single dose of a basic fraction of Ficus carica extract (n=14), diabetic rats who received a single dose of a chloroform fraction of the extract (n=10), and normal rats (n=10). Compared to normal animals, the diabetic animals presented significantly higher values for erythrocyte catalase normalized to haemoglobin levels (1.5+/-0.15 vs. 0.96+/-0.18 microg/mg) and for plasma vitamin E (73.4+/-43.9 vs. 12.0+/-1.6 mg/l), monounsaturated fatty acids (0.219+/-0.118 vs. 0.067+/-0.014 mg/ml), polyunsaturated fatty acids (PUFA, 0.567+/-0.293 vs. 0.175+/-0.040 mg/ml), saturated fatty acids (0.779+/-0.262 vs. 0.401+/-0.055 mg/ml), and linoleic acid (0.202+/-0.086 vs. 0.106 +/-0.014 mg/ml). Both Ficus carica fractions tended to normalize the values of the diabetic animals' fatty acids and plasma vitamin E values. On studying the ratios of vitamins E and A to PUFA (129.4+/-77.5 diabetic and 68.8+/-9.1 microg/mg normal; 37.5+/-20.8 vs. 108.0+/-43.6 microg/mg) and to C18:2 (259.9+/-65.8 vs. 161.0+/-21.3 microg/mg; 68.3+/-37.9 vs. 252.7+/-102.1 microg/mg), we found statistically significant differences as a function of diabetes, with the vitamin E/C18:2 ratio being normalized by the administration of the chloroform fraction (to 152.1+/-80.3 microg/mg) and the vitamin A/C18:2 ratio being raised relative to the untreated diabetic rats by the administration of the basic fraction (91.9+/-14.5 microg/mg). Our work confirms that antioxidant status is affected in the diabetes syndrome, and that Ficus carica extracts tend to normalize it.


Pereira, S. L., A. E. Leonard, et al. (2003). "Recent advances in the study of fatty acid desaturases from animals and lower eukaryotes." Prostaglandins Leukot Essent Fatty Acids 68(2): 97-106.

            The biosynthesis of polyunsaturated fatty acids (PUFAs) in different organisms can involve a variety of pathways, catalyzed by a complex series of desaturation and elongation steps. A range of different desaturases have been identified to date, capable of introducing double bonds at various locations on the fatty acyl chain. Some recently identified novel desaturases include a delta4 desaturase from marine fungi, and a bi-functional delta5/delta6 desaturase from zebrafish. Using molecular genetics approaches, these desaturase genes have been isolated, identified, and expressed in variety of heterologous hosts. Results from these studies will help increase our understanding of the biochemistry of desaturases and the regulation of PUFA biosynthesis. This is of significance because PUFAs play critical roles in multiple aspects of membrane physiology and signaling mechanisms which impact human health and development.


Pereira, S. L., Y. S. Huang, et al. (2003). "A novel omega3- (omega3-) fatty acid desaturase involved in the biosynthesis of eicosapentaenoic acid." Biochem J Pt.

            Long chain n-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA, 20:5n-3) have important therapeutic and nutritional benefits in humans. In plants, cyanobacteria, and nematodes, omega3-desaturases catalyze the formation of these n-3 fatty acids from n-6 fatty acid precursors. Here, we describe the isolation and characterization of a gene (sdd17) derived from an EPA-rich fungus Saprolegnia diclina that encodes a novel omega3-desaturase. This gene was isolated by PCR amplification of an S. diclina cDNA library using oligonucleotides primers corresponding to conserved regions of known omega3-desaturases. Expression of this gene in Saccharomyces cerevisiae, in the presence of various fatty acid substrates, revealed that the recombinant protein could exclusively desaturate 20-carbon n-6 fatty acid substrates with a distinct preference for arachidonic acid (ARA, 20:4n-6), converting it to EPA. This activity differs from that of the known omega3-desaturases from any organism. Plant and cyanobacteiral omega3-desaturases exclusively desaturate 18-carbon n-6 PUFAs, and a Caenorhabditis elegans omega3-desaturase preferentially desaturated 18-carbon PUFAs over 20-carbon substrates, and could not convert ARA to EPA when expressed in yeast. The sdd17-encoded desaturase was also functional in transgenic somatic soybean embryos, resulting in the production of EPA from exogenously supplied ARA, thus demonstrating its' potential for use in the production of EPA in transgenic oilseed crops.


Perassolo, M. S., J. C. Almeida, et al. (2003). "Fatty acid composition of serum lipid fractions in type 2 diabetic patients with microalbuminuria." Diabetes Care 26(3): 613-8.

            OBJECTIVE: To determine the fatty acid composition of serum phospholipid, triglyceride, and cholesterol ester fractions and to analyze the lipid profile of microalbuminuric type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A case-control study was conducted with 72 patients: 37 were normoalbuminuric (urinary albumin excretion rate [UAER] <20 microg/min), and 35 were microalbuminuric (UAER 20-200 microg/min). After 4 weeks of a standardized diet, the fatty acid composition of phospholipid, triglyceride, and cholesterol ester fractions was determined by gas chromatography. Total cholesterol and triglycerides were measured by enzymatic-colorimetric methods; cholesterol HDL by double precipitation with heparin, MnCl(2), and dextran sulfate; and apolipoprotein B by immunoturbidimetry. RESULTS: Microalbuminuric patients showed a lower proportion of polyunsaturated fatty acids (24.8 +/- 11.0%), especially of the n-6 family (21.7 +/- 10.5%), in triglyceride fraction than normoalbuminuric patients (34.1 +/- 11.3%, P = 0.001 and 31.4 +/- 11.5%, P < 0.001, respectively). Patients with microalbuminuria also presented higher levels of saturated fatty acids in triglyceride fraction (43.4 +/- 18.0% vs. 34.7 +/- 13.1%, P = 0.022). In the logistic regression analysis, only the proportion of polyunsaturated fatty acids in triglyceride fraction remained significantly associated with microalbuminuria (odds ratio [OR] 0.92, 95% CI 0.85-0.98, P = 0.019). Total cholesterol, HDL cholesterol, triglyceride, and apolipoprotein B levels were similar in normo- and microalbuminuric patients. CONCLUSION: Microalbuminuria in type 2 diabetic patients is associated with low polyunsaturated fatty acid contents in serum triglyceride fraction. This association may represent a risk factor for cardiovascular disease and may contribute to the progression of renal disease.


Peng, J., Y. Larondelle, et al. (2003). "Polyunsaturated fatty acid profiles of whole body phospholipids and triacylglycerols in anadromous and landlocked Atlantic salmon (Salmo salar L.) fry." Comp Biochem Physiol B Biochem Mol Biol 134(2): 335-48.

            We compared the fatty acid compositions and gains of whole body triacylglycerols (TAG) and phospholipids (PL) in anadromous and landlocked Atlantic salmon (Salmo salar) fry, of the same age, fed the same commercial marine oil-rich diet over a 42-day feeding trial. The landlocked strain exhibited significantly (P<0.05) higher growth rate and feed efficiency, due principally to a higher fat retention, particularly of monounsaturated and saturated fatty acids (SFA). n-3 and n-6 long-chain polyunsaturated fatty acid (PUFA) gains and retentions were significantly higher (P<0.05) in the landlocked fry. Great similarities were found in the fatty acid profiles of whole body TAG of both strains. However, marked genotypic differences were observed in the PUFA profiles of whole body PL fractions. The total PUFA, n-3 PUFA and docosahexaenoic acid (DHA) level in PL was significantly higher (P<0.05) while the SFA level, and the PUFA C18/C20 and eicosapentaenoic acid/arachidonic acid ratios were significantly lower (P<0.05) in the anadromous fry than in landlocked fry. Our results indicate that the level of DHA in salmon PL is under strong genetic control and that the capacity for incorporation, and possibly for the conversion of dietary n-3 and n-6 PUFA, is higher in the landlocked strain.


Pei, Z., N. A. Oey, et al. (2003). "The acyl-CoA synthetase "bubblegum" (lipidosin): further characterization and role in neuronal fatty acid beta-oxidation." J Biol Chem 278(47): 47070-8.

            Acyl-CoA synthetases play a pivotal role in fatty acid metabolism, providing activated substrates for fatty acid catabolic and anabolic pathways. Acyl-CoA synthetases comprise numerous proteins with diverse substrate specificities, tissue expression patterns, and subcellular localizations, suggesting that each enzyme directs fatty acids toward a specific metabolic fate. We reported that hBG1, the human homolog of the acyl-CoA synthetase mutated in the Drosophila mutant "bubblegum," belongs to a previously unidentified enzyme family and is capable of activating both long- and very long-chain fatty acid substrates. We now report that when overexpressed, hBG1 can activate diverse saturated, monosaturated, and polyunsaturated fatty acids. Using in situ hybridization and immunohistochemistry, we detected expression of mBG1, the mouse homolog of hBG1, in cerebral cortical and cerebellar neurons and in steroidogenic cells of the adrenal gland, testis, and ovary. The expression pattern and ability of BG1 to activate very long-chain fatty acids implicates this enzyme in the pathogenesis of X-linked adrenoleukodystrophy. In neuron-derived Neuro2a cells, mBG1 co-sedimented with mitochondria and was found in small vesicular structures located in close proximity to mitochondria. RNA interference was used to decrease mBG1 expression in Neuro2a cells and led to a 30-35% decrease in activation and beta-oxidation of the long-chain fatty acid, palmitate. These results suggest that in Neuro2a cells, mBG1-activated long-chain fatty acids are directed toward mitochondrial degradation. mBG1 appears to play a minor role in very long-chain fatty acid activation in these cells, indicating that other acyl-CoA synthetases are necessary for very long-chain fatty acid metabolism in Neuro2a cells.


Peet, M. (2003). "Eicosapentaenoic acid in the treatment of schizophrenia and depression: rationale and preliminary double-blind clinical trial results." Prostaglandins Leukot Essent Fatty Acids 69(6): 477-85.

            It has been hypothesised that polyunsaturated fatty acids (PUFA) play an important role in the aetiology of schizophrenia and depression. Evidence supporting this hypothesis for schizophrenia includes abnormal brain phospholipid turnover shown by 31P Magnetic Resonance Spectroscopy, increased levels of phospholipase A2, reduced niacin skin flush response, abnormal electroretinogram, and reduced cell membrane levels of n-3 and n-6 PUFA. In depression, there is strong epidemiological evidence that fish consumption reduces risk of becoming depressed and evidence that cell membrane levels of n-3 PUFA are reduced. Four out of five placebo-controlled double- blind trials of eicosapentaenoic acid (EPA) in the treatment of schizophrenia have given positive findings. In depression, two placebo-controlled trials have shown a strong therapeutic effect of ethyl-EPA added to existing medication. The mode of action of EPA is currently not known, but recent evidence suggests that arachidonic acid (AA) if of particular importance in schizophrenia and that clinical improvement in schizophrenic patients using EPA treatment correlates with changes in AA.


Pedersen, J. I., B. Kirkhus, et al. (2003). "Serum cholesterol predictive equations in product development." Eur J Med Res 8(8): 325-31.

            The aim of the study was to incorporate trans fatty acids into predictive equations for serum cholesterol and compare their effects with the effects of the individual saturated fatty acids 12:0, 14:0 and 16:0. We have introduced trans fatty acids from partially hydrogenated soybean oil (TransV) and fish oil (TransF) into previously published equations by constrained regression analysis. Prior knowledge about the signs and ordering of existing regression coefficients were incorporated into the regression modelling by adding lower and upper bounds to the coefficients. Oleic acid (18:1) and polyunsaturated fatty acids (18:2, 18:3) were not sufficiently varied in the studies and the respective regression coefficients therefore set equal to those found by Yu et al. (Am J Clin Nutr 1995;61:1129-39). Stearic acid (18:0) considered to be neutral was not included in the equations. The regression analyses were based on results from four controlled dietary studies with a total of 95 participants and including 10 diets differing in fatty acid composition. The analyses resulted in the following equations where the change in cholesterol is expressed in mmol/L and the change in intake of fatty acids is expressed in E%: Delta Total cholesterol = 0.01 delta(12:0) + 0.12 Delta(14:0) + 0.057 delta(16:0) + 0.039 delta(TransF) + 0.031 delta(TransV)- 0.0044 delta(18:1) - 0.017 delta(18:2, 18:3) and deltaLDL cholesterol = 0.01 delta(12:0) + 0.071 delta(14:0) + 0.047 delta(16:0) + 0.043 delta(TransF) + 0.025 delta(TransV) - 0.0044 delta(18:1) - 0.017 delta(18:2, 18:3). The test set used for validation consisted of 22 data points from seven recently published dietary studies. The equation for total cholesterol showed good prediction ability with a correlation coefficient of 0.981 between observed and predicted values. The equation has been used to reformulate margarines into "trans free" products all with more favourable effects on serum cholesterol than previous products. Also a cholesterol reducing margarine has been produced. When tested against butter in an open clinical trial among subjects with mild hypercholesterolemia the observed cholesterol-lowering effect of this margarine corresponded reasonably well with the predicted (0.77 vs. 0.64 mmol/L). We conclude that the equation has practical applicability and can be used to formulate and nutritionally optimise fat products as well as to evaluate already existing products on the market.


Pazos, A. J., J. L. Sanchez, et al. (2003). "Seasonal changes in lipid classes and fatty acid composition in the digestive gland of Pecten maximus." Comp Biochem Physiol B Biochem Mol Biol 134(2): 367-80.

            Seasonal variations in lipid classes and fatty acid composition of triacylglycerols and phospholipids in the digestive gland of Pecten maximus were studied over a period of 16 months. Acylglycerols predominated (19-77% of total lipids), in accordance with the role of the digestive gland as an organ for lipid storage in scallops. Seasonal variations were mainly seen in the acylglycerol content, while phospholipids (2.5-10.0% of total lipids) and sterols (1.9-7.4% of total lipids) showed only minor changes. The most abundant fatty acids were 14:0, 16:0, 18:0, 16:1(n-7), 18:1(n-9), 18:1(n-7), 18:4(n-3), 20:5(n-3) and 22:6(n-3) and these showed similar seasonal profiles in both, triacylglycerol and phospholipid fractions. In contrast to the phospholipid fraction, the triacylglycerol fraction contained more 20:5(n-3) than 22:6(n-3). In three phospholipid samples we noted a high percentage of a 22-2-non-methylene-interrupted fatty acid, previously described to have a structural role in several bivalve species. The main polyunsaturated fatty acids displayed important seasonal variations parallel to those of the acylglycerols, suggesting good nutritional conditions. A positive correlation existed between the level of saturated fatty acids and temperature, whereas the levels of polyunsaturated fatty acids correlated negatively with temperature.


Pawlosky, R. J., J. R. Hibbeln, et al. (2003). "Effects of beef- and fish-based diets on the kinetics of n-3 fatty acid metabolism in human subjects." Am J Clin Nutr 77(3): 565-72.

            BACKGROUND: The quantity and type of dietary polyunsaturated fatty acids (PUFAs) can alter essential fatty acid metabolism in humans. Diets rich in 20- and 22-carbon PUFAs may inhibit desaturase expression or activity and decrease the synthesis of long-chain unsaturated fatty acids. OBJECTIVE: It was theorized that the fat content of a fish-based diet would inhibit the kinetics of the in vivo metabolism of n-3 fatty acids compared with a beef-based diet. DESIGN: A compartmental model was used to determine the coefficients of the kinetic rate constants from the plasma concentration time curves of pentadeuterated (d(5)) 18:3n-3, 20:5n-3, 22:5n-3, and 22:6n-3 of 10 subjects who subsisted on 3 diets with different long-chain PUFA contents. For 3 wk, subjects reported their food intake from their usual diets and then consumed a beef-based diet for 3 wk and then a fish-based diet for an additional 3 wk. Subjects consumed 1 g d(5)-18:3n-3 ethyl ester at weeks 3, 6, and 9. Blood was drawn over 168 h and the plasma analyzed for fatty acids. The coefficients of the kinetic constants of n-3 fatty acid metabolism and the percentage utilization of the substrates were determined. RESULTS: Across all diets, < 1% of plasma 18:3n-3 was utilized for long-chain PUFA synthesis. There was a 70% reduction in the value of the rate constant coefficient that regulated transfer of the isotope from the 22:5n-3 compartment to 22:6n-3 when the fish-based diet was compared with the beef-based diet. The turnover rate of plasma d(5)-22:6n-3 also decreased. CONCLUSIONS: The primary effect of a fish-based diet on the kinetics of n-3 metabolism involves processes that inhibit the synthesis of 22:6n-3 from 22:5n-3. These processes may involve a system of feedback control mechanisms responsive to the plasma concentration of 22:6n-3.


Pater, C., D. Compagnone, et al. (2003). "Effect of Omacor on HRV parameters in patients with recent uncomplicated myocardial infarction - A randomized, parallel group, double-blind, placebo-controlled trial: study design [ISRCTN75358739]." Curr Control Trials Cardiovasc Med 4(1): 2.

            BACKGROUND: A large body of data derived from animal, epidemiological and clinical studies indicate that n-3 polyunsaturated fatty acids have a favourable effect on the prognosis of patients with cardiovascular disease in general, and on reducing sudden death in particular.Depressed heart rate variability (HRV), an indicator of impairment of the autonomic nervous system, has been shown to be a powerful predictor of subsequent mortality in patients surviving an acute myocardial infarction. A multitude of studies have demonstrated this strong association, suggesting that the imbalance in the sympathic/parasympathetic system may facilitate emergence of ventricular arrhythmias.Heart rate variability parameters will be assessed in the present study, with the primary objective of evaluating the possible superiority of Omacor (a highly refined, concentrated omega-3 fatty acid) versus placebo in improving HRV from baseline to endpoint in patients with recent uncomplicated myocardial infarction. Both groups will receive optimal conventional treatment.The study will also explore and quantify improvement in time domain HRV indices and will assess the safety of administering Omacor to optimally treated post-infarction patients (conventional treatment). METHODS: This multi-centre study will evaluate the effect of Omacor 1 g, o.d. on time-domain HRV parameters in comparison to placebo o.d. in patients with recent uncomplicated transmural myocardial infarction.Patients will be screened during the first few days after the acute event as appropriate for the patient's condition, and after obtaining informed consent. Based on inclusion/exclusion criteria, a first 24-hour Holter recording will be performed. Two to five days later, screened patients still eligible for the study will undergo a second 24-hour Holter recording. After the second Holter recording, all patients will be randomly allocated to treatment with Omacor 1 g, o.d. or placebo o.d.One hundred patients will be followed in double-blind fashion for a six-month period after randomization. Visits, including 24-hour Holter recording and assessment of adverse events, will take place at one-month intervals +/- five days after randomization, i.e., six times in all.


Passi, S., A. Stancato, et al. (2003). "Statins lower plasma and lymphocyte ubiquinol/ubiquinone without affecting other antioxidants and PUFA." Biofactors 18(1-4): 113-24.

            It has been shown that treating hypercholesterolemic patients (HPC) with statins leads to a decrease, at least in plasma, not only in cholesterol, but also in important non-sterol compounds such as ubiquinone (CoQ10), and possibly dolichols, that derive from the same biosynthetic pathway. Plasma CoQ10 decrease might result in impaired antioxidant protection, therefore leading to oxidative stress. In the present paper we investigated the levels in plasma, lymphocytes and erythrocytes, of ubiquinol and ubiquinone, other enzymatic and non-enzymatic lipophilic and hydrophilic antioxidants, polyunsaturated fatty acids of phosfolipids and cholesterol ester fractions, as well as unsaturated lipid and protein oxidation in 42 hypercholesterolemic patients treated for 3 months. The patients were treated with different doses of 3 different statins, i.e. atorvastatin 10 mg (n = 10) and 20 mg (n = 7), simvastatin, 10 mg (n = 5) and 20 mg (n = 10), and pravastatin, 20 mg (n = 5) and 40 mg (n = 5). Simvastatin, atorvastatin and pravastatin produced a dose dependent plasma depletion of total cholesterol (t-CH), LDL-C, CoQ10H2, and CoQ10, without affecting the CoQ10H2/CoQ10 ratio. The other lipophilic antioxidants (d-RRR-alpha-tocopherol-vit E-, gamma-tocopherol, vit A, lycopene, and beta-carotene), hydrophilic antioxidants (vit C and uric acid), as well as, TBA-RS and protein carbonyls were also unaffected. Similarly the erythrocyte concentrations of GSH and PUFA, and the activities of enzymatic antioxidants (Cu,Zn-SOD, GPx, and CAT) were not significantly different from those of the patients before therapy. In lymphocytes the reduction concerned CoQ10H2, CoQ10, and vit E; other parameters were not investigated. The observed decline of the levels of CoQ10H2 and CoQ10 in plasma and of CoQ10H2, CoQ10 and vit E in lymphocytes following a 3 month statin therapy might lead to a reduced antioxidant capacity of LDL and lymphocytes, and probably of tissues such as liver, that have an elevated HMG-CoA reductase enzymatic activity. However, this reduction did not appear to induce a significant oxidative stress in blood, since the levels of the other antioxidants, the pattern of PUFA as well as the oxidative damage to PUFA and proteins resulted unchanged. The concomitant administration of ubiquinone with statins, leading to its increase in plasma, lymphocytes and liver may cooperate in counteracting the adverse effects of statins, as already pointed out by various authors on the basis of human and animal studies.


Papina, M., T. Meziane, et al. (2003). "Symbiotic zooxanthellae provide the host-coral Montipora digitata with polyunsaturated fatty acids." Comp Biochem Physiol B Biochem Mol Biol 135(3): 533-7.

            We compared the fatty acid composition of the host-coral Montipora digitata with the fatty acid composition in the coral's endosymbiotic dinoflagellates (zooxanthellae). Fatty acids as methyl esters were determined using gas chromatography (GC) and verified by GC-mass spectrometry. We found the main difference between the fatty acids in the host and their symbionts were that zooxanthellae supported higher proportions of polyunsaturated fatty acids. The presence of fatty acids specific to dinoflagellates (i.e. 18:4omega3, 22:5omega3 and 22:6omega3) in the host tissue suggests that zooxanthellae provide the coral host not only with saturated fatty acids, but also with diverse polyunsaturated fatty acids.


Paoloni-Giacobino, A., R. Grimble, et al. (2003). "Genomic interactions with disease and nutrition." Clin Nutr 22(6): 507-14.

            The putative influence of genomic factors on the responsiveness to nutrient intake is a newly developed field of research. As well, there is growing interest for determining the interactions between nutrient, inflammation and aging and the possible impact on lifespan and disease development. Inflammation adversely affects health in many diseases with an inflammatory basis, such as atherosclerosis, obesity and type 2 diabetes mellitus. The metabolic effects of inflammation are mediated by pro-inflammatory cytokines. Metabolic effects include insulin insensitivity, hyperlipidemia, muscle protein loss and oxidant stress. Aging is also characterized by an increase in inflammatory stress and contains some of the hallmarks of inflammatory disease. It is also a phase of life when inflammatory diseases rise in incidence. Evidence is accumulating that the individual level of cytokine production is influenced by single nucleotide polymorphisms (SNPs) in cytokine genes. The combination of SNPs might control the relative level of inflammatory stress following inflammatory stimuli and diseases. These genomic characteristics might therefore influence lifespan, morbidity and mortality in diseases with an infectious or inflammatory basis.Recent studies indicate that genotypic factors may influence the effectiveness of such immunonutrients as anti-oxidants and n-3 polyunsaturated fatty acids. A better understanding of this aspect of nutrient gene interactions and of the genomic factors which influence the intensity of inflammation in disease will help in the targeting of nutritional therapy.


Panchenko, V. M., A. A. Ershov, et al. (2003). "[Long-term administration of tyquanol in the treatment of patients with ischemic heart disease in combination with hyperlipidemia]." Klin Med (Mosk) 81(3): 40-2.

            33 patients with coronary heart disease and hyperlipidemia took tyquanol for 6 months. Tyquanol is a complex of biologically active substances represented by polyunsaturated fatty acids, antioxidants and polyvitamins produced of dietary oils of the sea and plant origin. As a result of the treatment with tyquanol cholesterol, beta-lipoproteins, triglycerides lowered by 16.1, 11.1, 26.3%, respectively. Alphipoproteins rose by 8.8%. A negative effect on hepatic, renal functions or electrolyte composition was not observed.


Palacios, A., V. Piergiacomi, et al. (2003). "Antioxidant effect of conjugated linoleic acid and vitamin A during non enzymatic lipid peroxidation of rat liver microsomes and mitochondria." Mol Cell Biochem 250(1-2): 107-13.

            In the study reported here the effect of conjugated linoleic acid (CLA) and vitamin A on the polyunsaturated fatty acid composition, chemiluminescence and peroxidizability index of microsomes and mitochondria isolated from rat liver was analyzed. The effect of CLA on the polyunsaturated fatty acid composition of native microsomes was evidenced by an statistically significant p < 0.007 decrease of linoleic acid C18:2 n6, whereas in mitochondria it was observed a decrease p < 0.0001 of arachidonic acid C20:4 n6 when compared with vitamin A and control groups. Docosahexaenoic acid C22:6 n3 in mitochondria was reduced p < 0.04 in CLA and vitamin A groups when compared with control. After incubation of microsomes or mitochondria in an ascorbate (0.4 mM)-Fe++ (2.15 microM) system (120 min at 37 degrees C) it was observed that the total cpm/mg protein originated from light emission: chemiluminescence was lower in liver microsomes or mitochondria obtained from CLA group (received orally: 12.5 mg/daily during 10 days) than in the vitamin A group (received intraperitoneal injection: daily 0.195 g/ kg during 10 days). CLA reduced significantly maximal induced chemiluminescence in microsomes relative to vitamin A and control groups, whereas in mitochondria the effect was observed relative to control group. The polyunsaturated fatty acid composition of liver microsomes or mitochondria changed by CLA and vitamin A treatment. The polyunsaturated fatty acids mainly affected when microsomes native and peroxidized from control group were compared were linoleic, linolenic and arachidonic acids, while in vitamin A group linoleic and arachidonic acid were mainly peroxidized, whereas in CLA group only arachidonic acid was altered. In mitochondria obtained from the three groups arachidonic acid and docosahexaenoic acid showed a significant decrease when native and peroxidized groups were compared. As a consequence the peroxidizability index, a parameter based on the maximal rate of oxidation of fatty acids, show significant changes in the CLA group compare vitamin A and control groups. The simultaneous analysis of peroxidizability index, chemiluminescence and fatty acid composition demonstrated that CLA is more effective than vitamin A protecting microsomes or mitochondria from peroxidative damage.


Ovide-Bordeaux, S. and A. Grynberg (2003). "Dietary Docosahexaenoic Acid Affects the Alterations Induced in Rat Cardiac Mitochondrial Function in Insulin Deficiency and Insulin Resistance." Am J Physiol Regul Integr Comp Physiol.

            The effect of docosahexaenoic acid (DHA) intake on cardiac mitochondrial function was evaluated in permeabilized fibers in insulin deficiency and insulin-resistance in rats. The insulin deficient state was obtained by streptozotocin injection 2 months before investigations. Insulin resistance was obtained by feeding a 62% fructose diet for three months. DHA was incorporated in the diet to modify the fatty acid composition of cardiac membranes, including mitochondria. Insulin deficiency decreased mitochondrial creatine kinase (mi-CK) activity and mitochondrial sensitivity to ADP. DHA intake prevented these alterations. Moreover, the insulin deficient state significantly decreased n-3 polyunsaturated fatty acids (PUFA) and slightly increased n-6 PUFA in both cardiac and mitochondrial membranes, inducing a significant increase in n-6/n-3 ratio. DHA intake maintained high myocardial and mitochondrial DHA content. Insulin deficiency also decreased glutamate and palmitoylcarnitine-supported mitochondrial respiration, but DHA intake did not prevent these effects. In contrast, insulin resistance did not affect mi-CK activity or sensitivity to ADP. However, insulin resistance influenced the myocardial fatty acid composition with decreased n-6 and n-3 PUFA contents and increased monounsaturated fatty acid content. Only slight alterations were observed in mitochondrial fatty acid composition and they were corrected by DHA intake. Moreover, insulin resistance decreased the glutamate-supported respiration, and DHA intake did not influence this effect. In conclusion, the impairment of cardiac mitochondrial function was more pronounced in insulin deficient state than in insulin resistance. The modification of fatty acid composition of cardiac and mitochondrial membranes by DHA partially prevented the mitochondrial alterations induced in the two models.


Ould El Kebir, M. V., G. Barnathan, et al. (2003). "Fatty acid distribution in muscle, liver, and gonads of rays (Dasyatis marmorata, Rhinobatos cemiculus, and Rhinoptera marginata) from the East Tropical Atlantic Ocean." J Agric Food Chem 51(7): 1942-7.

            If a great number of rays are fished in the Tropical East Atlantic Ocean for their caudal fins, only a small amount of ray flesh is processed. Among them, three species of rays, Dasyatis marmorata, Rhinobatos cemiculus, and Rhinoptera marginata, from the Mauritanian coast have been investigated for the fatty acid composition of their lipids. Gas chromatography and gas chromatography-mass spectrometry allowed identification of 50 molecules from muscles, livers, and gonads of these fishes. Principal component analysis, starting from >50 samples, reveals significant differences in various fatty acid distributions, related to the species and sex of the sampled fish. Some of them are preferentially present in one sex or in both species, whereas the occurrence of others characterizes the male and female of one or two species. The results show that rays are potential resources of polyunsaturated fatty acids (PUFA) and should be used in the diet of local populations. The lipidic fractions contained a high amount of PUFA (up to 30% of the total), mainly composed of docosa-4,7,10,13,16,19-hexaenoic acid, eicosa-5,8,11,14-tetraenoic acid, and eicosa-5,8,11,14,17-pentaenoic acid.


Osochuk, S. S. (2003). "[Comparative characteristics of changes in the fatty acid spectrum of high density lipoproteins in male patients of various age with appendicitis]." Klin Lab Diagn(8): 22-4, 33.

            The fatty acid spectrum, the content of cholesterol of total high-density lipoproteins (HDLP) and high-density lipoproteins3 as well as the activity of lecithin-cholesteryl-acyl-transferase (LCAT) were investigated in mature-age males (periods I and II) with appendicitis. The intensity of endogenous production of polyunsaturated fatty acids was concluded to be reducing in mature-age (periods I and II) males. As for the mature-age males of period I, the consumption of polyunsaturated fatty acids was found to be increasing and the production of endogenous cholesterol was found to be decreasing in them. The transformation of HDLP3 into HDLP2 was found to be declerating in the mature-males of period II, while the cholesterol-acceptor ability of HDLP3 was going up in the males of latter category.


Omodeo-Sale, F., A. Motti, et al. (2003). "Accelerated senescence of human erythrocytes cultured with Plasmodium falciparum." Blood 102(2): 705-11.

            Red blood cells infected withPlasmodium falciparum(IRBCs) undergo changes primarily in their membrane composition that contribute to malaria pathogenesis. However, all manifestations (eg, anemia) cannot be accounted for by IRBCs alone. Uninfected erythrocytes (URBCs) may play a role, but they have been under-researched. We wanted to document changes in the erythrocyte membrane that could contribute to URBC reduced life span and malaria-associated anemia. Human erythrocytes were cultured withP falciparumand washed at the trophozoite stage. IRBCs and URBCs were separated on Percoll density gradient, thus obtaining erythrocyte fractions of different densities/ages. IRBC- and URBC-purified membranes were analyzed and compared with control normal erythrocytes (NRBCs) of the same age, from the same donor, kept in the same conditions.P falciparumaccelerated aging of both IRBCs and URBCs, causing a significant shift in the cell population toward the denser (old) fraction. Protein, phospholipid, and cholesterol content were reduced in IRBCs and young URBCs. Young and medium uninfected fractions had higher levels of lipid peroxidation and phospholipid saturation (because of the loss of polyunsaturated fatty acids, PUFAs) and lower phosphatidylserine. In IRBCs, thiobarbituric reactive substances (TBARSs) were higher, and PUFAs and phosphatidylserine lower than in NRBCs and URBCs. In comparison, trophozoite membranes had lower phospholipid (particularly sphingomyelin and phosphatidylserine) and cholesterol content and a higher degree of saturation. Parasite-induced peroxidative damage might account for these modifications. In summary, we demonstrated that membrane damage leading to accelerated senescence of both infected and uninfected erythrocytes will likely contribute to malaria anemia.


Olson, R. E. (2003). "Nutrition and genetics: an expanding frontier." Am J Clin Nutr 78(2): 201-8.

            The age of molecular biology began in 1953 with the discovery of the structure of DNA. By 1961 the genetic code for the translation of the sequence of bases in DNA to amino acids in proteins was underway, and a model for the genetic regulation of protein synthesis was proposed. My interest in the genetic regulation of nutrient metabolism began in that year during my sabbatical leave in the laboratory of Sir Hans Krebs at Oxford University. In the present article, I describe 2 episodes in my career during which I used genetic concepts to explain a nutritional phenomenon; the first episode occurred before doing the experimental work, and the second occurred after the experimental work was completed. My first brainstorm, which occurred in 1961, was to investigate the hypothesis that all of the fat-soluble vitamins act by the regulation of a cluster of genes. Unfortunately, I selected vitamin K as my model and discovered that it is the only fat-soluble vitamin that does not work in full or in part by the regulation of a set of genes. In 1967 I undertook a second problem, which was to determine the mode of action of polyunsaturated fatty acids in lowering plasma lipid concentrations in humans. We discovered that linoleic acid reduced the storage and enhanced the oxidation of fatty acids. The genetic interpretation of this study has come only recently: polyunsaturated fats have been shown to down-regulate enzymes that accomplish storage of fatty acids and to up-regulate genes that enhance fatty acid oxidation.


Ollivier, D., J. Artaud, et al. (2003). "Triacylglycerol and fatty acid compositions of French virgin olive oils. Characterization by chemometrics." J Agric Food Chem 51(19): 5723-31.

            There is no data concerning the fatty acid and triacylglycerol composition of French virgin olive oil. Thus, these compositions were determined using 564 samples coming from four olive harvests (1998-1999 to 2000-2001). Among these 564 samples, 372 came from the four main French cultivars (Aglandau, Cailletier, Picholine, and Salonenque) and from both of the oldest French protected designations of origin: "Nyons" (cv. Tanche) and "Vallee des Baux". The fatty acid compositions took the different isomeric monounsaturated fatty acids (C16:1 and C18:1) into account. The eicosenoic acid is gondoic acid (20:1n-9) and was determined by dimethyl disulfide adduct using GC/MS. The use of propionitrile as a mobile phase for the HPLC analysis of the triacylglycerols led to better resolutions between triacylglycerols than those resolutions obtained with the mix of solvents recommended by the normalized method (acetone/acetonitrile). Of the samples, 88 had a 9-heptadecenoic acid level (17:1n-8) higher than 0.3% and 33 had a linolenic acid level higher than 0.9%, which are maximal values accepted by the International Olive Oil Council and the European Union. A linear discriminant analysis was carried out on 372 samples with the SAS system and particularly with STEPISC and CANDISC procedures. Variables (n = 37) representing the different fatty acids, the sum of saturated, monounsaturated, and polyunsaturated fatty acids, squalene, and triacylglycerols were used, thus allowing us to classify samples into six groups defined with 100% of well classified samples. These results constitute an original data bank that can be used to identify the origin of virgin olive oils.


Okada, M., H. Nakanishi, et al. (2003). "How does prolonged caloric restriction ameliorate age-related impairment of long-term potentiation in the hippocampus?" Brain Res Mol Brain Res 111(1-2): 175-81.

            Prolonged dietary restriction has been reported to suppress age-induced phenomena. In order to investigate how prolonged caloric restriction reduces age-related deterioration of hippocampal synaptic transmission, we compared the levels of major hippocampal polyunsaturated fatty acids, arachidonic acid and docosahexaenoic acid between 4- and 26-month-old rats. The Ca(2+) responses upon perfusion of NMDA or 30 mM K(+) between 4- and 26-month-old rats with prolonged dietary restriction were also compared using the fluorescent probe Fura-2. A decrease in membrane arachidonic acid is thought to be a major causal factor in the age-related impairment of long-term potentiation. Long-term caloric restriction seems to increase arachidonic acid levels regardless of age. However, there is no significant difference of hippocampal arachidonic acid levels between in freely feeding 4- and 26-month-old rats. Similar results were obtained from the measurement of hippocampal docosahexaenoic acid levels. Under caloric restriction, the 500 microM N-methyl-D-aspartate-induced Ca(2+) response was greatly reduced by aging, while the 30 mM K(+)-induced Ca(2+) response was not affected. In our preliminary data, the amplitude of the population spike after tetanic stimulation did not differ between 4- and 26-month-old rats under caloric restriction, while 50 microM of 2-amino-5-phosphonovaleric acid, a N-methyl-D-aspartate antagonist, markedly inhibited a potentiation of the population spike in 4-month-old rats, but with negligible inhibition in 26-month-old rats. From these results, an age-related impairment of hippocampal excitatory synaptic transmission may not be solely due to the reduction of membrane arachidonic acid. Caloric restriction might prevent age-related reduction in hippocampal synaptic transmission by enhancing non-N-methyl-D-aspartate mechanisms.


Ogita, H., K. Node, et al. (2003). "Eicosapentaenoic acid reduces myocardial injury induced by ischemia and reperfusion in rabbit hearts." J Cardiovasc Pharmacol 41(6): 964-9.

            Intake of fish oil is known to have cardioprotective effects and reduce cardiovascular mortality. However, it is not widely recognized that eicosapentaenoic acid (EPA), one of the n-3 polyunsaturated fatty acids (PUFAs), exerts beneficial effects against myocardial ischemia/reperfusion injury. The purpose of this study is to investigate whether EPA attenuates the severity of myocardial ischemia/reperfusion injury and which cellular mechanism is involved. Rabbits were treated with or without EPA (600 mg/kg/day) for 2 weeks. Infarct size was measured in open-chest rabbits after 30-minute occlusion of the left anterior descending coronary artery (LAD) and after the subsequent 3-hour reperfusion. In several groups, NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, or charybdotoxin, a blocker of calcium-activated potassium (K(Ca)) channels, was infused intravenously beginning 20 minutes before LAD occlusion and continuing during reperfusion. Infarct size was reduced in the group treated with EPA compared with the control group (7.2 +/- 1.0% vs 24.6 +/- 2.3%; P < 0.01). The occurrence of ventricular arrhythmias in the reperfusion period tended to decrease in the EPA group. Either L-NAME or charybdotoxin partially blunted or completely abolished the infarct size-limiting effect of EPA, respectively. Eicosapentaenoic acid significantly increased the n-3:n-6 ratio of PUFA. Eicosapentaenoic acid reduces myocardial infarct size, mainly via the opening of K(Ca) channel-mediated and partially NO-mediated mechanisms in rabbit hearts.


Ochoa, J. J., M. C. Ramirez-Tortosa, et al. (2003). "Oxidative stress in erythrocytes from premature and full-term infants during their first 72 h of life." Free Radic Res 37(3): 317-22.

            OBJECTIVE: The aim of this study was to evaluate the extent of lipid peroxidation and the response of the enzymatic and non-enzymatic antioxidant defence system in erythrocytes from full-term and premature infants at birth, after 3 and after 72 h of life. STUDY DESIGN: Twenty infants were selected and divided in two groups according to their gestational age. Blood samples were taken at birth, at 3 and at 72 h of life, erythrocytes were isolated and the following parameters were measured: fatty-acid profile, coenzyme Q, alpha-tocopherol, hydroperoxides and the activity of the antioxidant enzymes catalase, superoxide dismutase (SOD) and cytosolic glutathione peroxidase (cGPx). RESULTS: For the three studied periods, several differences between full-term and premature infants were found. Premature children showed a higher concentration of hydroperoxides, a lower level of alpha-tocopherol and lower SOD and cGPx activity (except for cGPx at birth). Moreover, n-3 polyunsaturated fatty-acids percentages (essential for good neonatal development) were higher in full term children throughout all the study. CONCLUSION: Results suggest a strong imbalance between oxidants and antioxidants in premature infants during their first 72 h of life, a situation which could lead to several pathologies. Therefore, further research is needed, including possible nutritional intervention (with antioxidant therapy, supplementation of essential fatty acids and other dietary constituents) before and after birth.


Ochoa, J. J., J. L. Quiles, et al. (2003). "Aging-related oxidative stress depends on dietary lipid source in rat postmitotic tissues." J Bioenerg Biomembr 35(3): 267-75.

            We investigate mitochondrial-lipid peroxidation of mitotic (liver) and postmitotic (heart and skeletal muscle) tissues of rats fed lifelong on two different lipid sources: virgin olive oil (monounsaturated fatty acids) and sunflower oil (n - 6 polyunsaturated fatty acids). Two groups of 80 rats each were fed over 24 months on a diet differing in the lipid source (virgin olive oil or sunflower oil). Twenty rats per group were killed at 6, 12, 18, and 24 months; liver, heart, and skeletal muscle mitochondria were isolated and the lipid profile, hydroperoxides, vitamin E, and ubiquinone as well as catalase activity measured. Lipid peroxidation was higher in postmitotic tissues, and sunflower oil led to a higher degree of polyunsaturation and peroxidation. The levels of alpha-tocopherol adapted to oxidative stress and preferentially accumulated during aging in heart and skeletal muscle. In conclusion, the type of dietary fat should be considered in studies on aging, since oxidative stress is directly modulated by this factor. This study confirms that postmitotic tissues are more prone to oxidative stress during aging and proposes a hypothesis to explain this phenomenon.


O'Neill, S. (2003). "Anti-arrhythmic actions of polyunsaturated fatty acids in cardiac muscle exerted via the sarcoplasmic reticulum." Biochem Soc Trans 31(Pt 5): 939-42.

            Cardiac arrhythmias can be triggered from ischaemic cardiac muscle due to the damage inflicted on individual myocytes. During an ischaemic episode free fatty acids accumulate in the ischaemic tissue. The importance of these fatty acids lies in the apparent ability of some classes of fatty acid to protect against cardiac arrhythmias. As cardiac sudden death is a likely cause of death in patients who have suffered an initial ischaemic insult, protection against such arrhythmias may be of crucial importance. The following review discusses how this protection may be produced, dealing specifically with changes in electrophysiological properties of cells and intracellular calcium regulation.


O'Neill, C. M., S. Gill, et al. (2003). "Natural variation for seed oil composition in Arabidopsis thaliana." Phytochemistry 64(6): 1077-90.

            The biochemical pathways involved in the biosynthesis and accumulation of storage lipids in seeds have been extensively studied. However, the regulatory mechanisms of those pathways, their environmental interactions and the ecological implications of variation are poorly understood. We have initiated a new approach: the analysis of natural variation in Arabidopsis thaliana. Three hundred and sixty accessions were surveyed for content of oil, very long chain fatty acids (VLCFAs) and polyunsaturated fatty acids (PUFAs) in their seeds. The results revealed extensive natural variation. A core set of accessions, the seeds of which reproducibly contain extreme amounts of oil, VLCFAs and PUFAs have been identified. Reproducible oil content ranged from 34.6 to 46.0% of seed dry weight. VLCFA content ranged from 13.0 to 21.2% of total fatty acids. PUFA content, ranged from 53.3 to 66.1% of total fatty acids. Interactions were also identified for PUFA and VLCFA content of seeds with vernalisation of plants. Mapping of the regions of the genome involved in controlling the traits was conducted in an F(2) population and indicated that natural variation at the loci FAE1 and FAD3 might be involved in the regulation of VLCFA and PUFA content, respectively. A set of accessions, which capture a broad range of the natural variation for these traits available in A. thaliana, has been selected to form a core set which can be used to further dissect the genetics of the regulation of seed lipid traits and to identify the genes involved.


Nydahl, M. C., R. D. Smith, et al. (2003). "Achievement of dietary fatty acid intakes in long-term controlled intervention studies: approach and methodology." Public Health Nutr 6(1): 31-40.

            OBJECTIVE: To describe the calculations and approaches used to design experimental diets of differing saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) compositions for use in a long-term dietary intervention study, and to evaluate the degree to which the dietary targets were met. DESIGN, SETTING AND SUBJECTS: Fifty-one students living in a university hall of residence consumed a reference (SFA) diet for 8 weeks followed by either a moderate MUFA (MM) diet or a high MUFA (HM) diet for 16 weeks. The three diets were designed to differ only in their proportions of SFA and MUFA, while keeping total fat, polyunsaturated fatty acids (PUFA), trans-fatty acids, and the ratio of palmitic to stearic acid, and n-6 to n-3 PUFA, unchanged. RESULTS: Using habitual diet records and a standardised database for food fatty acid compositions, a sequential process of theoretical fat substitutions enabled suitable fat sources for use in the three diets to be identified, and experimental margarines for baking, spreading and the manufacture of snack foods to be designed. The dietary intervention was largely successful in achieving the fatty acid targets of the three diets, although unintended differences between the original target and the analysed fatty acid composition of the experimental margarines resulted in a lower than anticipated MUFA intake on the HM diet, and a lower ratio of palmitic to stearic acid compared with the reference or MM diet. CONCLUSIONS: This study has revealed important theoretical considerations that should be taken into account when designing diets of specific fatty acid composition, as well as practical issues of implementation.


Nwankwo, J. O., A. A. Spector, et al. (2003). "A nucleotide insertion in the transcriptional regulatory region of FADS2 gives rise to human fatty acid delta-6-desaturase deficiency." J Lipid Res 44(12): 2311-9.

            Fatty acid delta-6-desaturase (FADS2) is the rate-limiting enzyme in mammalian synthesis of long-chain polyunsaturated fatty acids. We investigated the molecular mechanism of FADS2 deficiency in skin fibroblasts from a patient deficient in this enzyme. Expression analyses demonstrated an 80% to 90% decrease in the steady-state level of FADS2 mRNA in patient-derived cells compared with normal controls that was consistent with previous metabolic biochemical studies. In vitro transcription assays indicated an 80% decrease in the rate of transcriptional initiation in patient-derived cells, thus implicating transcriptional regulation as the mechanism for the decreased transcript levels. Sequence analysis of the 5' end of the gene revealed the insertion of a thymidine between positions -941 and -942 upstream of the translation start site in patient-derived cells compared with normal cells and published sequences. Promoter-reporter assays demonstrated a 6-fold decrease in promoter activity in the polymorphic variant FADS2 regulatory region compared with the normal gene, confirming the functional relevance of the insertion mutation to the decreased expression of the gene in the patient-derived cells. These findings indicate that fatty acid delta-6-desaturase deficiency and decreased FADS2 transcription are caused by a nucleotide insertion in the transcriptional regulatory region of the human FADS2 gene.


Nkondjock, A., B. Shatenstein, et al. (2003). "Specific fatty acids and human colorectal cancer: an overview." Cancer Detect Prev 27(1): 55-66.

            BACKGROUND: Evidence suggests that dietary fats are associated with risk of colorectal cancer. The effect of fats depends not only on the quantity, but also on their composition in specific fatty acids. Moreover, fats are peroxidizable, and peroxidation products as well as antioxidants play a role in the pathogenic process of colorectal cancer. METHODS: The published literature was reviewed for the relationship between dietary intake or concentration of specific fatty acids in adipose tissue, erythrocytes, plasma or feces in relation to colorectal cancer. RESULTS: Increased concentrations of short-chain fatty acids (SCFAs) and eicosanopentaenoic acid (EPA) seem to protect against colorectal cancer. Increased concentrations of medium-chain fatty acids (MCFAs) and arachidonic acid (AA) might be associated with increased risk. Long-chain saturated fatty acids (LCSFAs) seem unrelated to colorectal cancer, while the associations between monounsaturated fatty acids (MUFAs), trans fatty acids, polyunsaturated fatty acids (PUFAs) such as linoleic acid (LA), alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), omega-3/omega-6 ratio and colorectal cancer are unconvincing. CONCLUSIONS: It is suggested that the substitution of food with high MCFAs and AA content by a SCFAs- and EPA-rich diet may contribute to reduced risk of colorectal cancer.


Nkondjock, A., B. Shatenstein, et al. (2003). "Assessment of risk associated with specific fatty acids and colorectal cancer among French-Canadians in Montreal: a case-control study." Int J Epidemiol 32(2): 200-9.

            BACKGROUND: Discrepancies in findings on the association between dietary fats and colorectal cancer (CRC) persist, and it is hypothesized that fatty acids (FA) may modulate CRC risk because of their physiological functions. METHODS: Between 1989 and 1993, a case-control study involving 402 cases and 668 population-based controls was conducted among French-Canadians. Dietary intake was assessed by a food frequency questionnaire. RESULTS: Oleic acid was the major FA consumed by the study population. A significant inverse association was found among females between CRC and butyrate (OR = 0.57; 95% CI: 0.34-0.96; P = 0.006), alpha-linoleic acid (ALA) (OR = 0.78; 95% CI: 0.46-1.32; P = 0.016), and w-3 FA (OR = 0.84; 95% CI: 0.50-1.41; P = 0.028), comparing the upper to the lower quartiles of intake. An increased risk was associated with arachidonic acid (AA) (OR = 2.03; 95% CI: 1.16-3.54; P = 0.001) among males, and with the w6/w3 ratio (OR = 1.47; 95% CI: 0.86-2.50; P = 0.001) among females. Arachidonic acid was linked with up to fivefold increased risk (OR = 5.33; 95% CI: 2.04-13.95; P = 0.0004 for trend) among men with high vitamin C intake. Females with low carotenoids intake were at elevated risk associated with AA (OR = 4.07; 95% CI: 1.84-8.99; P = 0.003); eicosapentaenoic acid (OR = 3.50; 95% CI: 1.59-7.71; P = 0.015), and docosahexaenoic acid (OR = 5.77; 95% CI: 2.50-13.33; P = 0.002), comparing the upper with the lower quartiles of intake. CONCLUSION: The results of this study suggest that independently of total energy intake, substituting AA by butyrate, ALA, or omega-3 FA may reduce CRC risk. The role of interactions between vitamin C, total carotenoids, and polyunsaturated FA requires further investigation.


Nkondjock, A., B. Shatenstein, et al. (2003). "A case-control study of breast cancer and dietary intake of individual fatty acids and antioxidants in Montreal, Canada." Breast 12(2): 128-35.

            This case-control study was conducted among French-Canadians to assess the association between breast cancer risk and specific fatty acids, and to investigate if breast cancer risk associated with individual polyunsaturated fatty acids differs in regard to antioxidant intakes. A total of 414 cases and 429 population-based controls were interviewed between 1989 and 1993. Dietary intake was assessed by a food-frequency questionnaire. No overall association was found between specific fatty acids and breast cancer risk, after adjustment for risk factors and total energy intake. In postmenopausal women with low vitamin E intake, there was an inverse and dose-dependent relationship between arachidonic acid and breast cancer risk [odds ratio (OR)=0.41; 95% confidence interval (CI) (0.20-0.82); P=0.02], while those with high vitamin E intake exhibited a significantly elevated risk [OR=2.46; 95% CI (1.12-5.39); P=0.024] when comparing the upper to the lower quartiles. The possible role of the interaction effect between arachidonic acid and vitamin E in breast cancer risk requires further investigation.


Nichols, D. S. (2003). "Prokaryotes and the input of polyunsaturated fatty acids to the marine food web." FEMS Microbiol Lett 219(1): 1-7.

            The investigation of prokaryotes in aquatic ecology is often limited to their role in nutrient cycling and the degradation of organic matter. While this aspect of the microbial loop is undoubtedly important, further aspects of bacterial roles in marine food webs exist which have not been fully considered in light of recent research in related fields. The concept of bacteria providing essential nutrients may derive importance from two aspects of their role in the marine environment; firstly as a primary food source for omnivorous, sestonivorous and filtering benthic animals and secondly as components of the commensal microbial communities of marine animals. Many marine organisms lack the de novo ability to produce n-3 polyunsaturated fatty acids (PUFA) and hence rely on a dietary supply of PUFA. The issue of PUFA origin in the marine food web is particularly salient in light of recent research demonstrating the influence of PUFA levels on the efficiency of energy transfer between trophic levels. The assumption that microalgae provide the bulk of de novo PUFA production for all marine food webs must be actively reviewed with respect to particular microbial niches such as sea ice, marine animals and abyssal communities.


Newman, R. E., L. H. Storlien, et al. (2003). "Dietary n-3 and n-6 fatty acids alter avian pituitary sensitivity." Nutr Neurosci 6(6): 343-50.

            The effects of dietary saturated and polyunsaturated fatty acids (PUFAs) of the n-3 and n-6 series on avian pituitary sensitivity were investigated by infusing human growth hormone (GH) releasing hormone--fragment 1-29--and chicken luteinising hormone releasing hormone (LHRH) into catheterized broiler chickens. At 3 weeks of age three groups (n = 18; six birds per group) were fed for 6 weeks isonitrogenous and isoenergetic experimental diets containing 80 g/kg of edible tallow (saturated fatty acids), fish oil (n-3 PUFAs) or sunflower oil (n-6 PUFAs). Jugular catheterisation was performed under general anaesthesia during week four of the dietary treatments and the birds allowed 7 days post surgery to recover. A bolus of LHRH (20 microg/bird) and a GH releasing hormone (12.5 microg/kg) infusion was given on different days to each chicken and serial blood samples taken over a 1 h period. Plasma luteinising hormone and GH concentrations were measured by radioimmunoassay. Pre-infusion GH concentrations were similar for the tallow, fish and sunflower oil dietary groups (5.2 +/- 3.9, 5.2 +/- 1.0 and 6.1 +/- 3.1 ng/ml, respectively), however, GH concentration in response to the GH releasing hormone infusion was elevated in the sunflower oil group (44.7 +/- 5.7 ng/ml) when compared to chicken fed tallow (33.7 +/- 9.7ng/ml) or fish oil (21.3 +/- 5.0 ng/ml). There was a significant decrease (P < 0.05) in the clearance rate of plasma GH for the birds fed the fish oil compared with those fed sunflower oil with an intermediate value being observed in the tallow fed group. Pre-infusion plasma luteinising hormone concentrations for the birds fed tallow (3.2 +/- 0.7 ng/ml) were significantly elevated (P < 0.05) when compared to birds fed either the sunflower oil (0.84 +/- 0.25 ng.ml) or fish oil (0.93 +/- 0.22 ng/ml) diets. There were no significant differences between the dietary groups in either the maximal plasma luteinising concentration or its disappearance rate following the LHRH infusion. The data demonstrate that dietary fatty acids alter avian pituitary sensitivity and this modulation is determined by the nature of the dietary fat rather than the degree of saturation per se. In addition, this study also shows that dietary fats have a differential effect on pituitary cell activity and are specific to certain pituitary cell types.


Nestares, T., M. Lopez-Jurado, et al. (2003). "Effects of lifestyle modification and lipid intake variations on patients with peripheral vascular disease." Int J Vitam Nutr Res 73(5): 389-98.

            The aim of the present study was to evaluate the effects of diets enriched in monounsaturated fatty acids (MUFA) (olive oil) or MUFA plus n-3 polyunsaturated fatty acids (PUFA) (olive oil plus fish oil), associated with an intervention program that focused on lifestyle habits, physical performance, plasma lipids, and lipoprotein composition in patients with peripheral vascular disease (PVD). A 15-month longitudinal nutritional and lifestyle intervention study was carried out with 24 free-living male patients aged 58.0 +/- 2.2 years diagnosed with PVD (Fontaine grade II). The patients were clinically evaluated and counseled to change their dietary and lifestyle habits for six months, after this period they consumed an olive oil-based diet for three months: after a three-month wash-out period, their diet was supplemented with a combination of fish oil and olive oil for the final three months. Lifestyle interventions resulted in a significant decrease in cigarette smoking and an increase in physical activity. Claudicometry was lower at the end of the study than at the beginning. Intake of the fish oil supplement led to significant changes in lipid lipoprotein composition, decreasing low-density lipoprotein (LDL) cholesterol. The lifestyle intervention program, together with a high intake of olive plus fish oil, seems to produce important beneficial effects in nutritional management, physical performance, and clinical parameters of PVD patients.


Negre-Salvayre, A., O. Vieira, et al. (2003). "Oxidized LDL and 4-hydroxynonenal modulate tyrosine kinase receptor activity." Mol Aspects Med 24(4-5): 251-61.

            Among the diverse risk factors involved in atherosclerosis, LDL are thought to become atherogenic after undergoing oxidative modifications, characterized by oxidized lipid formation and structural alterations of apoB. Oxidized LDL alter various signaling pathways and exhibit a broad range of biological responses including inflammation, gene expression, cell proliferation or apoptosis. The biological effects of oxidized LDL are related to the presence of peroxidation products such as hydroperoxides, lysophosphatidylcholines, oxysterols and aldehydes.4-Hydroxynonenal (HNE) is one of the most abundant aldehydes formed during the oxidation of polyunsaturated fatty acids in LDL and in membranes. It is able to react with thiols and free amino group residues of proteins. HNE is involved in apoB modifications that alter LDL metabolism and cell protein-adduct formation which may mediate in part the biological effects of oxidized LDL. We report here that HNE delivered to cells by oxidized LDL reacts with cellular proteins, for instance with tyrosine kinase receptors (RTK) such as EGFR and PDGFR. HNE induces in vitro derivatization and tyrosine phosphorylation of RTK (the fine molecular mechanism and conformational changes remain to be elucidated). In intact living cells, oxidized LDL (and pure HNE) trigger HNE-adduct formation and activation of PDGFR and EGFR, through an antioxidant-insensitive and reactive oxygen species independent mechanism. The presence of HNE-PDGFR adducts in atherosclerotic areas lead one to hypothesize that oxidized lipids may also react in vivo with membrane RTK, thereby disturbing their cellular functions.


Navia, B., R. M. Ortega, et al. (2003). "Influence of maternal education on food consumption and energy and nutrient intake in a group of pre-school children from Madrid." Int J Vitam Nutr Res 73(6): 439-45.

            A study was conducted on the influence of maternal education level on food consumption, energy and nutrient intake, and dietary adequacy in 110 pre-school children from Madrid, Spain. With increasing maternal education, children consumed more sugar(p < 0.05), fruit (p < 0.05), and fish (p < 0.05). Snacking was more frequent with decreasing maternal education (p < 0.05). Though statistical significance was not reached, the consumption of pre-cooked foods was greater among children of mothers educated to a higher level, a phenomenon probably related to the work situation of these women. With respect to dietary composition, no significant differences were found between groups for macronutrient, fiber and energy intakes, except for energy supplied by polyunsaturated fatty acids (PUFA), which was greater in the children of less educated women (p < 0.01). This is probably due to their greater consumption of sunflower seed oil. The diets of children belonging to well-educated mothers came closer to meeting the recommended intakes for folate, vitamin C, and iodine. It would seem that maternal educational level influences the food habits of children. Mothers with less education may require special advice in this area.


Navarro, J. L., F. R. Barri, et al. (2003). "Physical characteristics and chemical composition of Lesser Rhea (Pterocnemia pennata) eggs from farmed populations." Br Poult Sci 44(4): 586-90.

            1. Eggs from 4 farmed populations of Lesser Rhea (Pterocnemia pennata) were studied to determine their physical and chemical characteristics. 2. None of the physical variables (weight of whole egg, yolk, albumen and shell; proportion of yolk based on egg content; proportion of shell based on entire egg weight; volume; density) showed significant differences between populations. 3. Among chemical variables, moisture, both saturated fatty acids (palmitic 16:0 and stearic 18:0), one monounsaturated fatty acid (palmitoleic 16:1), and one polyunsaturated fatty acid (arachidonic 20:4), did not differ between populations, whereas other variables (protein, lipid and ash contents; fatty acids: oleic 18:1, linoleic 18:2, linolenic 18:3; PUFA; PUFA/SFA; cholesterol) differed significantly.


Narayanan, B. A., N. K. Narayanan, et al. (2003). "Modulation of inducible nitric oxide synthase and related proinflammatory genes by the omega-3 fatty acid docosahexaenoic acid in human colon cancer cells." Cancer Res 63(5): 972-9.

            Epidemiological and preclinical studies demonstrate that consumption of diets high in omega-3 polyunsaturated fatty acids reduces the risk of colon cancer. Inhibition of colon carcinogenesis by omega-3 polyunsaturated fatty acids is mediated through modulation of more than one signaling pathway that alters the expression of genes involved in colon cancer growth. In our earlier studies on global gene expression with cDNA microarrays, we have shown that treatment of CaCo-2 colon cancer cells with docosahexaenoic acid (DHA) down-regulated the prostaglandin family of genes, as well as cyclooxygenase 2 expression and several cell cycle-related genes, whereas it up-regulated caspases 5, 8, 9, and 10 that are associated with apoptosis. It is known that nitric oxide activates the cyclooxygenase 2 enzyme, which plays a pivotal role in the progression of colon cancer via prostaglandin synthesis and angiogenesis. The present study was undertaken to examine the multifaceted role of DHA in the expression of inducible nitric oxide synthase (iNOS) and of related proinflammatory genes, as those have been shown to play a role in tumor progression. In addition, we aimed to identify associated target genes by DNA microarray, reverse transcription-PCR analysis, and cellular localization of iNOS expression in CaCo-2 cells. Results of this study demonstrate that treatment with DHA down-regulates iNOS in parallel with a differential expression and down-regulation of IFNs, cyclic GMP, and nuclear factor kappa B isoforms. More importantly, our findings clearly demonstrate the up-regulation of cyclin-dependent kinase inhibitors p21((Waf1/Cip1)) and p27, differentiation-associated genes such as alkaline phosphatases, and neuronal differentiation factors. These finding strongly suggest that the antitumor activity of DHA may be attributed, at least in part, to an effect on iNOS regulatory genes. In addition, our results indicate the presence of specific gene expression profiles in human colon cancer that can be used as molecular targets for chemopreventive agents.


Napolitano, M., M. Avella, et al. (2003). "Chylomicron remnant induction of lipid accumulation in J774 macrophages is associated with up-regulation of triacylglycerol synthesis which is not dependent on oxidation of the particles." Biochim Biophys Acta 1631(3): 255-64.

            The influence of chylomicron remnants on lipid accumulation and synthesis and the activity and/or expression of mRNA for some of the key enzymes involved was investigated in the murine macrophage cell line J774. The effects of varying the polyunsaturated fatty acid (PUFA) composition and oxidation state of the remnants were also examined. Chylomicron remnants derived from corn oil (rich in n-6 PUFA) or fish oil (rich in n-3 PUFA) were prepared in vivo and oxidised by incubation with CuSO(4). The native and oxidised remnants caused a marked rise in intracellular triacylglycerol levels, but the rise induced by corn oil remnants (four- to sixfold) was greater than that observed with fish oil remnants (<2-fold). Triacylglycerol synthesis, as measured by the incorporation of [3H]oleate and [3H]glycerol into cellular triacylglycerol, was increased by all four remnant types tested, and corn oil remnants had a significantly greater effect than fish oil remnants. Oxidation of the remnants did not affect the results obtained. Although the incorporation of [3H]oleate into cholesteryl ester by the cells was not significantly changed by any of the four types of remnants tested, the activity and expression of mRNA for acyl Co-enzyme A: cholesterol acyltransferase (ACAT) was increased by corn oil, but not by fish or oxidised corn, remnants. Neutral cholesteryl ester hydrolase (nCEH) activity, however, was also raised by corn oil remnants. These studies indicate that chylomicron remnants induce the accumulation of triacylglycerol in J774 macrophages, and that increased synthesis of triacylglycerol plays a major role in this process. Furthermore, they demonstrate that these effects are enhanced when the remnants are enriched in n-6 PUFA as compared with n-3 PUFA, but not after oxidation of the particles, suggesting that the fatty acid composition of chylomicron remnants may be more important than their oxidation state in their ability to induce foam cell formation.


Napier, J. A., L. V. Michaelson, et al. (2003). "The role of cytochrome b5 fusion desaturases in the synthesis of polyunsaturated fatty acids." Prostaglandins Leukot Essent Fatty Acids 68(2): 135-43.

            The biosynthetic pathway of polyunsaturated fatty acids (PUFAs) has been the subject of much interest over the last few years. Significant progress has been made in the identification of the enzymes required for PUFA synthesis; in particular, the fatty acid desaturases which are central to this pathway have now all been identified. These "front-end" desaturases are all members of the cytochrome b(5) fusion desaturase superfamily, since they contain an N-terminal domain that is orthologous to the microsomal cytochrome b(5). Examination of the primary sequence relationships between the various PUFA-specific cytochrome b(5) fusion desaturases and related fusion enzymes allows inferences regarding the evolution of this important enzyme class. More importantly, this knowledge helps underpin our understanding of polyunsaturated fatty acid biosynthesis.


Nano, J. L., C. Nobili, et al. (2003). "Effects of fatty acids on the growth of Caco-2 cells." Prostaglandins Leukot Essent Fatty Acids 69(4): 207-15.

            Epidemiological studies suggest that polyunsaturated fatty acids may protect against colorectal neoplasia. In order to explore this observation, cell proliferation and viability, lipid composition, membrane fluidity, and lipid peroxidation were measured in Caco-2 cells after 48h incubation with various fatty acids. Saturated and monounsaturated fatty acids incorporated less well in the membranes than polyunsaturated fatty acids (PUFAs). All of the PUFAs tested had an inhibitory effect on cell proliferation/viability whereas the saturated and monounsaturated fatty acids did not. Addition of palmitic acid had no significant effect on membrane fluidity whereas unsaturated fatty acids increased membrane fluidity in a dose-dependent manner. PUFAs strongly increased tumor cell lipid peroxidation in a dose-dependent manner. Saturated and monounsaturated fatty acids increased lipid peroxidation in this cell line only at high concentration. Preincubation of Caco-2 cells with vitamin E prevented the inhibition of proliferation/viability, the elevation of the MDA concentration and the increased membrane fluidity induced by PUFAs. Our data indicate that PUFAs are potent inhibitors of the growth of colon cancer cells in vitro.


Nakamura, T., A. Azuma, et al. (2003). "Serum fatty acid levels, dietary style and coronary heart disease in three neighbouring areas in Japan: the Kumihama study." Br J Nutr 89(2): 267-72.

            CHD mortality is extremely low in Japan, particularly in rural districts, when compared with that in Western countries. This has been partly attributed to the difference in dietary lifestyle. We investigated the factors influencing CHD mortality in a rural coastal district of Japan, comprising mercantile, farming, and fishing areas with distinct dietary habits. We prospectively examined the incidence of CHD from 1994 to 1998, as well as coronary risk factors and serum fatty acid concentrations. The incidence of angina pectoris was significantly (P=0.01) lower in the fishing area than in the mercantile and farming areas. Blood pressure, physical activity, prevalence of diabetes, serum levels of uric acid and HDL-cholesterol were similar between the three areas. Total- and LDL-cholesterol levels were significantly lower but the smoking rate was markedly higher in the fishing area than in the other two areas. Serum levels of saturated fatty acids and n-6 polyunsaturated fatty acids (PUFA) were lowest in the fishing area, but n-3 PUFA did not differ significantly. The n-6:n-3 PUFA ratio was lowest and eicosapentaenoic:arachidonic acid was highest in the fishing area. Although many previous studies have emphasized the beneficial effect of n-3 PUFA in preventing CHD, the present study indicated that a lower intake of n-6 PUFA and saturated fatty acids has an additional preventive effect on CHD even when the serum level of n-3 PUFA is high because of high dietary fish consumption.


Nagler, L. G., V. Z. Lankin, et al. (2003). "Rate of free-radical oxidation of C18 diene and triene fatty acids in aqueous micellar solutions and effectiveness of beta-carotene as an inhibitor of their oxidation." Biochemistry (Mosc) 68(2): 203-8.

            The rate of accumulation of conjugated dienes of polyunsaturated fatty acids was measured during free-radical oxidation of linoleic acid (18:2n-6, LA), alpha-linolenic acid (18:3n-3, alpha-LNA), and gamma-linolenic acid (18:3n-6, gamma-LNA) initiated by 2,2;-azo-bis-(2-amidinopropane) hydrochloride in aqueous micellar solutions of sodium dodecyl sulfate and sodium cholate. It was shown that, unlike homogeneous solutions, the oxidative stability of PUFAs in aqueous dispersions increased with an increase in the extent of unsaturation. The rate of LA oxidation was more than tenfold greater than that of alpha- and gamma-LNA. The antioxidant activity of beta-carotene, in contrast to homogeneous solutions, in both micellar systems studied depended on the degree of PUFA unsaturation. We found that 5 micro M beta-carotene effectively inhibited the LA oxidation (almost by 90%), whereas the oxidation of alpha-LNA and gamma-LNA was not inhibited by beta-carotene even at much greater concentration (30 micro M). The paradoxical discrepancy between the extent of unsaturation and the PUFA oxidation rate, as well as a decrease in the efficiency of beta-carotene-dependent inhibition of oxidation of more polyunsaturated fatty acids in reactions conducted in aqueous dispersions is consistent with the model according to which the peroxyl radicals of LA and fatty acids with the double-bond number greater than two exhibit different polarity.


Nafstad, P., W. Nystad, et al. (2003). "Asthma and allergic rhinitis at 4 years of age in relation to fish consumption in infancy." J Asthma 40(4): 343-8.

            It has been suggested that consumption of fish and polyunsaturated fatty acids could have a protective effect against inflammation in the airways and the development of asthma and other allergic diseases. Our objective was to test the hypothesis that fish consumption during the first year of life decreases the risk of childhood asthma and allergic rhinitis. We assessed the relation between introduction of fish in the diet during the first year of life and risk of asthma and allergic rhinitis in a prospective 4-year cohort study of 2531 Norwegian children. We estimated odds ratios (OR) in logistic regression analysis adjusting for potential confounders. A total of 47.6% children had fish during the first year of life. The adjusted OR for allergic rhinitis was 0.45 (95% confidence interval [CI]=0.28, 0.74) and for asthma 0.84 (95% CI=0.57, 1.22). Fish consumption in the first year of life may reduce the risk of developing asthma and allergic rhinitis in childhood.


Muth, A., A. Mosandl, et al. (2003). "Multidimensional gas chromatography-mass spectrometry for tracer studies of fatty acid metabolism via stable isotopes in cultured human trophoblast cells." J Chromatogr B Analyt Technol Biomed Life Sci 791(1-2): 235-44.

            The determination of placental fatty acid metabolism using stable isotope-labeled tracers was investigated in the human placental choriocarcinoma (JAR) cell line. Stable isotope incorporation was measured by MDGC-MS. The cultured trophoblast cells incorporated and metabolized the essential fatty acids to long-chain polyunsaturated fatty acids. The described method enables the detection of a low Delta(6)-desaturase activity in this human placental cell line. The developed MDGC-MS method allows the assessment of long-chain polyunsaturated fatty acid biosynthesis in cultured cells with high sensitivity and selectivity. In this respect, tracer studies with MDGC-MS will be a powerful tool to clarify the significance of placental fatty acid metabolism.


Musavi, S. and P. Kakkar (2003). "Effect of diazepam treatment and its withdrawal on pro/antioxidative processes in rat brain." Mol Cell Biochem 245(1-2): 51-6.

            Exploratory studies were undertaken to ascertain the role of pro/antioxidative processes during a 3 weeks administration of low sub-toxic dose of diazepam and its withdrawal. Rats were administered 3 mg/kg diazepam for 21 consecutive days and the changes observed in different regions of rat brain at the sub-cellular level. Mitochondria from cerebrum showed a 27% lowering of TBARS whereas those from cerebellum and brain stem showed 48 and 24% enhanced MDA levels respectively. No significant alteration in the SOD isozymes was observed after the dose schedule. The mitochondrial glutathione reductase (GR) activity showed a decrease in all the regions with maximum decrease (36%) recorded in brain stem while post mitochondrial fraction showed significant lowering in cerebrum (37%). Total -SH content increased in all the three regions with maximum enhancement recorded in cerebellum while the free thiol content also showed significant changes (p < 0.001) in cerebellum and brain stem. One week after the withdrawal of the drug MDA levels decreased by 38% in cerebrum and 53% each in mitochondrial fractions of cerebellum and brain stem. Regional heterogeneity in response was also observed in the post mitochondrial fractions. Mn-SOD showed lowered activity in cerebellum (22%) and in brain stem (15%). The mitochondrial GR activity decreased in all the regions being highest in cerebrum with no significant change in post mitochondrial fractions. The total and free -SH content in the withdrawn animals increased by 46% in cerebellum with no change in the other two regions. The results indicate towards lower oxidative phenomenon during 3 weeks treatment with diazepam while abrupt withdrawal causes lowering of antioxidant defenses which showed regional heterogeneity. A decrease in peroxidative decomposition of polyunsaturated fatty acids of membranes was observed on withdrawal, which could be due to stabilisation of membranes after long-term binding of diazepam.


Murphy, K. J., N. J. Mann, et al. (2003). "Fatty acid and sterol composition of frozen and freeze-dried New Zealand Green Lipped Mussel (Perna canaliculus) from three sites in New Zealand." Asia Pac J Clin Nutr 12(1): 50-60.

            In view of previously reported anti-inflammatory bioactivity of the New Zealand Green Lipped Mussel (NZGLM), the overall lipid profile and fatty acid and sterol composition of the NZGLM from various sites in New Zealand (Hallam Cove, Port Ligar. Little Nikau) were investigated using thin layer chromatography (TLC) and gas liquid chromatography (GLC). Samples were either frozen (F) or freeze-dried (FD) soon after collection. It was also thought prior to the study, there may be differences in the dietary sources of phytoplankton between the sites, responsible for the bioactivity, however data collected in New Zealand reported no difference in the type of phytoplankton, but a difference in the quantity. There were no major significant differences in the major components of the lipid, fatty acid and sterol composition between FD or frozen samples, nor were there any significant differences in the major composition between sites. The only major difference was between total lipid composition of the freeze-dried and frozen samples due to the removal of water during freeze-drying. Total lipid content on a dry weight basis in FD samples was 8.4 g/100 g tissue and was significantly higher than frozen samples (P < 0.05) and there was no significant site variation. The lipid class content between sites was also not significantly different as judged by TLC. Triglyceride (TG) lipid fraction appeared to be the most prominent in the frozen and FD samples. The free fatty acid (FFA) band was the next most prominent band and was visually more prominent in the frozen samples. Sterol esters (SE) were detected in higher amounts in the frozen samples compared with the FD samples. Phospholipid (PL) and sterols (ST) were distributed throughout all samples. Polyunsaturated fatty acids (PUFA) were the main group of fatty acids in both FD and frozen samples (45-46%), most of which were omega-3 (n-3) fatty acids (40-41%). Saturated fatty acids (SFA) accounted for approximately one quarter of total fatty acids, with little variation between FD and frozen samples. The major fatty acids of the NZGLM were docosahexaenoic acid (DHA: 22:6 n-3) (19% in both FD and frozen samples), eicosapentaenoic acid (EPA; 20:5 n-3) and palmitic acid (16:0) (15% in both FD and frozen samples). Cholesterol was the most prominent sterol (31% of total sterols). Other major sterols included desmosterol/brassicasterol (co-eluting), 24-methylenecholesterol, trans-22-dehydrocholesterol, 24-nordehydrocholesterol and occelasterol. This study is unique as it compares the lipid composition of the NZGLM from three sites in New Zealand with the additional effect of processing. This is the second comparative study investigating the lipid, fatty acid and sterol composition of the NZGLM with added interest in the effect of freeze-drying on the lipid content of the mussel. This study showed that there were no major significant differences in lipid, sterol and fatty acid composition between the FD and frozen samples of the NZGLM for three sites in New Zealand. Food chain studies and further research is warranted to investigate the presence and role of major and minor lipid components of the NZGLM.


Muller, H., A. S. Lindman, et al. (2003). "The serum LDL/HDL cholesterol ratio is influenced more favorably by exchanging saturated with unsaturated fat than by reducing saturated fat in the diet of women." J Nutr 133(1): 78-83.

            We compared the effects of a high fat diet [38.4% of energy (E%) from fat; HSAFA diet, polyunsaturated/saturated fatty acid (P/S) ratio = 0.14], a low fat diet (19.7 E% from fat; LSAFA diet, P/S = 0.17), both based on coconut oil, and a diet with a high content of mono- and polyunsaturated fatty acids (PUFA; 38.2 E% from fat; HUFA diet, P/S = 1.9) on serum lipoproteins. The 25 women studied consumed each diet for 3-wk periods in a crossover design. The two high fat diets were identical except for the quality of the test fat. The LSAFA diet was identical to the HSAFA diet except that half the fat was replaced by carbohydrates. Serum total cholesterol, LDL cholesterol and apoB concentrations did not differ between the HSAFA and the LSAFA diet periods. Total cholesterol, LDL cholesterol and apoB were lower when women consumed the HUFA diet than when they consumed the other two diets. HDL cholesterol and apoA-I were 15 and 11%, respectively, higher when women consumed the HSAFA diet than when they consumed the LSAFA diet; HDL cholesterol and apoA-I were lower when women consumed the HUFA diet than when they consumed the HSAFA diet, but not the LSAFA diet. The LDL cholesterol/HDL cholesterol and apoB/apoA-I ratios were higher when women consumed the LSAFA diet than when they consumed the HSAFA diet. The LDL/HDL cholesterol ratio was higher when women consumed either the LSAFA or the HSAFA diet than when they consumed the HUFA diet, whereas apoB/apoA-I was higher when women consumed the LSAFA diet than when they consumed the HUFA diet. Triacylglycerol and VLDL cholesterol were higher when women consumed the LSAFA diet than when they consumed either the HSAFA or the HUFA diet. We conclude that, to influence the LDL/HDL cholesterol ratio, changing the proportions of dietary fatty acids may be more important than restricting the percentage of total or saturated fat energy, at least when derived mainly from lauric and myristic acids, both of which increase HDL cholesterol.


Muller, H., A. S. Lindman, et al. (2003). "A diet rich in coconut oil reduces diurnal postprandial variations in circulating tissue plasminogen activator antigen and fasting lipoprotein (a) compared with a diet rich in unsaturated fat in women." J Nutr 133(11): 3422-7.

            The effects of high and low fat diets with identical polyunsaturated/saturated fatty acid (P/S) ratios on plasma postprandial levels of some hemostatic variables and on fasting lipoprotein (a) [Lp(a)] are not known. This controlled crossover study compared the effects of a high fat diet [38.4% of energy (E%) from fat; HSAFA-diet, P/S ratio 0.14], a low fat diet (19.7 E% from fat; LSAFA-diet, P/S ratio 0.17), both based on coconut oil, and a diet with a high content of monounsaturated fatty acids (MUFA) and PUFA (38.2 E% from fat; HUFA-diet, P/S ratio 1.9) on diurnal postprandial levels of some hemostatic variables (n = 11) and fasting levels of Lp(a) (n = 25). The postprandial plasma concentration of tissue plasminogen activator antigen (t-PA antigen) was decreased when the women consumed the HSAFA-diet compared with the HUFA-diet (P = 0.02). Plasma t-PA antigen was correlated with plasminogen activator inhibitor type 1 (PAI-1) activity when the participants consumed all three diets (Rs = 0.78, P < 0.01; Rs = 0.76, P < 0.01; Rs = 0.66, P = 0.03; on the HSAFA-, the LSAFA- and the HUFA-diet, respectively), although the diets did not affect the PAI-1 levels. There were no significant differences in postprandial variations in t-PA activity, factor VII coagulant activity or fibrinogen levels due to the diets. Serum fasting Lp(a) levels were lower when women consumed the HSAFA-diet (13%, P < 0.001) and tended to be lower when they consumed the LSAFA-diet (5.3%, P = 0.052) than when they consumed the HUFA-diet. Serum Lp(a) concentrations did not differ when the women consumed the HSAFA- and LSAFA-diets. In conclusion, our results indicate that a coconut oil-based diet (HSAFA-diet) lowers postprandial t-PA antigen concentration, and this may favorably affect the fibrinolytic system and the Lp(a) concentration compared with the HUFA-diet. The proportions of dietary saturated fatty acids more than the percentage of saturated fat energy seem to have a beneficial influence on Lp(a) levels.


Mozzi, R., S. Buratta, et al. (2003). "Metabolism and functions of phosphatidylserine in mammalian brain." Neurochem Res 28(2): 195-214.

            Phosphatidylserine (PtdSer) is involved in cell signaling and apoptosis. The mechanisms regulating its synthesis and degradation are still not defined. Thus, its role in these processes cannot be clearly established at molecular level. In higher eukaryotes, PtdSer is synthesized from phosphatidylethanolamine or phosphatidylcholine through the exchange of the nitrogen base with free serine. PtdSer concentration in the nervous tissue membranes varies with age, brain areas, cells, and subcellular components. At least two serine base exchange enzymes isoforms are present in brain, and their biochemical properties and regulation are still largely unknown because their activities vary with cell type and/or subcellular fraction, developmental stage, and differentiation. These peculiarities may explain the apparent contrasting reports. PtdSer cellular levels also depend on its decarboxylation to phosphatidylethanolamine and conversion to lysoPtdSer by phospholipases. Several aspects of brain PtdSer metabolism and functions seem related to the high polyunsaturated fatty acids content, particularly docosahexaenoic acid (DHA).


Morris, M. C., D. A. Evans, et al. (2003). "Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease." Arch Neurol 60(7): 940-6.

            BACKGROUND: Dietary n-3 polyunsaturated fatty acids improve brain functioning in animal studies, but there is limited study of whether this type of fat protects against Alzheimer disease. OBJECTIVE: To examine whether fish consumption and intake of different types of n-3 fatty acids protect against Alzheimer disease. DESIGN: Prospective study conducted from 1993 through 2000, of a stratified random sample from a geographically defined community. Participants were followed up for an average of 3.9 years for the development of Alzheimer disease. PATIENTS: A total of 815 residents, aged 65 to 94 years, who were initially unaffected by Alzheimer disease and completed a dietary questionnaire on average 2.3 years before clinical evaluation of incident disease. MAIN OUTCOME MEASURES: Incident Alzheimer disease diagnosed in a structured neurologic examination by means of standardized criteria. RESULTS: A total of 131 sample participants developed Alzheimer disease. Participants who consumed fish once per week or more had 60% less risk of Alzheimer disease compared with those who rarely or never ate fish (relative risk, 0.4; 95% confidence interval, 0.2-0.9) in a model adjusted for age and other risk factors. Total intake of n-3 polyunsaturated fatty acids was associated with reduced risk of Alzheimer disease, as was intake of docosahexaenoic acid (22:6n-3). Eicosapentaenoic acid (20:5n-3) was not associated with Alzheimer disease. The associations remained unchanged with additional adjustment for intakes of other dietary fats and of vitamin E and for cardiovascular conditions. CONCLUSION: Dietary intake of n-3 fatty acids and weekly consumption of fish may reduce the risk of incident Alzheimer disease.


Moreno, J. J. and M. T. Mitjavila (2003). "The degree of unsaturation of dietary fatty acids and the development of atherosclerosis (review)." J Nutr Biochem 14(4): 182-95.

            Atherosclerosis is the principal contributor to the pathogenesis of myocardial and cerebral infarction, gangrene and loss of function in the extremities. It results from an excessive inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. Atherosclerotic lesions develop fundamentally in three stages: dysfunction of the vascular endothelium, fatty streak formation and fibrous cap formation. Each stage is regulated by the action of vasoactive molecules, growth factors and cytokines. This multifactorial etiology can be modulated through the diet. The degree of unsaturation of dietary fatty acids affects lipoprotein composition as well as the expression of adhesion molecules and other pro-inflammatory factors, and the thrombogenicity associated with atherosclerosis development. Thus, the preventive effects of a monounsaturated-fatty acid-rich diet on atherosclerosis may be explained by the enhancement of high-density lipoprotein-cholesterol levels and the impairment of low-density lipoprotein-cholesterol levels, the low-density lipoprotein susceptibility to oxidation, cellular oxidative stress, thrombogenicity and atheroma plaque formation. On the other hand, the increase of high-density lipoprotein cholesterol levels and the reduction of thrombogenicity, atheroma plaque formation and vascular smooth muscle cell proliferation may account for the beneficial effects of polyunsaturated fatty acid on the prevention of atherosclerosis. Thus, the advantages of the Mediterranean diet rich in olive oil and fish on atherosclerosis may be due to the modulation of the cellular oxidative stress/antioxidant status, the modification of lipoproteins and the down-regulation of inflammatory mediators.


Morel, S., C. Berthonneche, et al. (2003). "Insulin resistance modifies plasma fatty acid distribution and decreases cardiac tolerance to in vivo ischaemia/reperfusion in rats." Clin Exp Pharmacol Physiol 30(7): 446-51.

            1. The early stage of insulin resistance, also termed the 'prediabetic state', is characterized by the development of hyperinsulinaemia, which maintains normoglycaemia under fasting conditions. The metabolic disorders induced in myocardial cells during this stage of the disease may constitute a basis for an alteration of the tolerance of the heart to ischaemia and reperfusion. 2. To test this hypothesis, male Wistar rats were fed a 66% fructose diet for 4 weeks, inducing a prediabetic state. Rats were then subjected to in vivo left coronary artery ligation followed by reperfusion. Blood samples were collected for plasma lipid profile determination. 3. The prediabetic state significantly increased the severity of ischaemia-induced arrhythmias (arrhythmia score 1.4 +/- 0.2 vs 2.0 +/- 0.0 in control and fructose-fed rats, respectively; P < 0.05) and the size of infarction (infarct size 41.2 +/- 3.0 vs 56.0 +/- 2.0% in control and fructose-fed rats, respectively; P < 0.01). This alteration of the tolerance to in vivo ischaemia/reperfusion may be the consequence of an increase in mono-unsaturated fatty acids and a decrease in omega3 polyunsaturated fatty acids in fructose-fed-rats. 4. In conclusion, because it is known that the prediabetic state increases the incidence of cardiovascular diseases by promoting coronaropathy, our study suggests that this metabolic disorder may also affect the prognosis of heart disease by decreasing the tolerance of cardiomyocytes to ischaemic insults.


Montgomery, C., B. K. Speake, et al. (2003). "Maternal docosahexaenoic acid supplementation and fetal accretion." Br J Nutr 90(1): 135-45.

            Docosahexaenoic acid (DHA) (22 : 6n-3) is a polyunsaturated fatty acid that is an essential constituent of membranes, particularly of the nervous system. Infants acquire DHA from their mothers, either prenatally via the placenta or postnatally in milk. The present study aimed to test the hypothesis that maternal supplementation during the second and third trimesters of pregnancy enriches maternal and/or fetal DHA status. In a randomised, prospective, double-blind study 100 mothers received either fish-oil capsules containing 400 mg DHA/g (200 mg/d) (n 50), or placebo containing 810 mg oleic acid/g (400 mg/d) (n 50) from 15 weeks gestation until term. Venous blood samples were obtained from mothers at 15, 28 and 40 weeks, and from the umbilical cord at birth. Total fatty acids in plasma and erythrocytes were analysed by GC-MS. There were no significant differences between maternal groups in baseline DHA, as a proportion of total fatty acids (g/100 g total fatty acids) or concentration (nmol/ml), in plasma and erythrocytes. DHA concentrations in plasma at 28 weeks (P=0.02) and erythrocytes at both 28 weeks (P=0.03) and term (P=0.02) were 20 % higher in supplemented mothers than the placebo group. DHA accounted for a higher proportion of total fatty acids in erythrocytes of supplemented mothers at 28 weeks (P=0.003) and term (P=0.01). There were no significant differences between groups in DHA (g/100 g total fatty acids or nmol/l) in cord blood. Maternal DHA status was maximal in mid-trimester and declined to term, at a lower rate in supplemented compared with unsupplemented mothers. Maternal DHA supplementation significantly increases maternal DHA status and limits the last trimester decline in maternal status, aiding preferential transfer of DHA from mother to fetus.


Monserrat, J. M., L. A. Geracitano, et al. (2003). "Determination of lipid peroxides in invertebrates tissues using the Fe(III) xylenol orange complex formation." Arch Environ Contam Toxicol 45(2): 177-83.

            Reactive oxygen species (ROS) are subproducts of the oxidative metabolism known to initiate chain reactions with polyunsaturated fatty acids that generate lipid peroxides (LPO). The objective of this work was to adapt the ferrous oxidation/xylenol orange (FOX) assay to measure LPO in invertebrate tissues i.e.: from polychaeta (Laeonereis acuta) and crab (Chasmagnathus granulata) species. Whole polychaetes were homogenized in methanol 100%, being determined the optimal sample volume and the time required for color development. It was tested five sample volumes (8-30 microl), following color development up to 215 min. Absorbance stabilization was observed after 90 min, being linearly related with sample volume. A similar procedure was adopted for crab tissues (anterior gills, posterior gills, and hepatopancreas). Differences between species and between organs of the same species were observed when analyzed nonspecific absorbance increments after adding the standard cumene hydroperoxide (CHP). In polychaeta and crab anterior gills tissue, absorbance increments were lower (21-25%) than samples without tissue extracts (blanks) that received CHP. In crab posterior gills and hepatopancreas, the nonspecific increment was almost negligible. Correction formulae are given to account for these differences and simplified protocols for each tissue and species are also included. Great differences in the lipid peroxides content was detected between worms (127.05 +/- 19.32 nmoles CHP/g of wet tissue) respect to anterior gills, posterior gills, and hepatopancreas from the crab species (52.65 +/- 3.59, 30.54 +/- 4.73, and 48.51 +/- 8.78 nmoles CHP/g of wet tissue, respectively).


Monge-Rojas, R., T. Alfaro Calvo, et al. (2003). "Comparison of serum concentration and dietary intake of alpha-tocopherol in a sample of urban and rural Costa Rican adolescents." Arch Latinoam Nutr 53(2): 165-71.

            Results from several studies have suggested that vitamin E intake could inhibit the progression of atherosclerotic lesions. Therefore, this study was designed to evaluate Costa Rican adolescents' serum alpha-tocopherol levels and their correlation with Body Mass Index (BMI) and the dietary intake of vitamin E and saturated and polyunsaturated fat. Ninety-five healthy, non-smoking adolescents and non-vitamin supplement users (aged 13-18) from urban and rural areas in San Jose, Costa Rica, were included in this study. Serum levels of lipid adjusted alpha-tocopherol were significantly higher in rural adolescents compared with urban youngsters (4.192 mumol/mmol +/- 0.831 and 3.486 mumol/mmol +/- 0.996, respectively). Likewise, reported mean daily 1000 kcal adjusted-vitamin E intake was higher in rural adolescents than in urban youngsters (9.2 +/- 3.7 mg. 16.0 +/- 8.7 mg). An important correlation was observed between intake of energy from saturated fat and adjusted-alpha-tocopherol serum levels (r = 0.430). Contrariwise, they correlated poorly with dietary alpha-tocopherol (r = 0.273), suggesting that serum is not a good biomarket of intake for alpha-tocopherol. Additionally, our results showed a negative relationship between BMI and adjusted-serum vitamin E levels (beta = 0.189; CI 95% -0.153, -0.013). The analysis of vitamin E intake showed that over 25% of adolescents have inadequate intake of the nutrient. This study suggests that nutritionists and pediatricians should encourage alpha-tocopherol intake and monitor the food sources of the nutrient and the adolescents' body weight as part of the strategies aimed at developing a healthy lifestyle.


Miyazaki, M., M. J. Jacobson, et al. (2003). "Identification and characterization of murine SCD4, a novel heart-specific stearoyl-CoA desaturase isoform regulated by leptin and dietary factors." J Biol Chem 278(36): 33904-11.

            Stearoyl-CoA desaturase (SCD) is the rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids. Thus far, three isoforms of SCD (SCD1, SCD2, and SCD3) have been identified and characterized. Regulation of the SCD1 isoform has been shown to be an important component of the metabolic actions of leptin in liver, but the effects of leptin on SCD isoforms in other tissues have not been investigated. We found that although the mRNA levels of SCD1 and SCD2 were not affected by leptin deficiency in the hearts of ob/ob mice, the SCD activity and levels of monounsaturated fatty acids were increased, implying the existence of another SCD isoform. This observation has led to the cDNA cloning and characterization of a fourth SCD isoform (SCD4) that is expressed exclusively in the heart. SCD4 encodes a 352-amino acid protein that shares 79% sequence identity with the SCD1, SCD2, and SCD3 isoforms. Liver X receptor alpha (LXR alpha) agonists and a high carbohydrate fat-free diet induced SCD4 expression, but unlike SCD1, SCD4 expression was not repressed by dietary polyunsaturated fatty acids. SCD4 mRNA levels were elevated 5-fold in the hearts of leptin-deficient ob/ob mice relative to wild type controls. Treatment of ob/ob mice with leptin decreased mRNA levels of SCD4, whereas levels of SCD1 and SCD2 were not affected. Furthermore, in the hearts of SCD1-deficient mice, SCD4 mRNA levels were induced 3-fold, whereas the levels of SCD2 were not altered. The current studies identify a novel heart-specific SCD isoform that demonstrates tissue-specific regulation by leptin and dietary factors.


Mitchell, D. C., S. L. Niu, et al. (2003). "DHA-rich phospholipids optimize G-Protein-coupled signaling." J Pediatr 143(4 Suppl): S80-6.

            OBJECTIVE: To assess the effects of n-3 polyunsaturated phospholipid acyl chains on the initial steps in G-protein-coupled signaling. STUDY DESIGN: Isolated components of the visual signal transduction system, rhodopsin, G protein (G(t)), and phosphodiesterase (PDE), were reconstituted in membranes containing various levels of n-3 polyunsaturated phospholipid acyl chains. In addition, rod outer segment disk membranes containing these components were purified from rats raised on n-3-deficient and n-3-adequate diets. The conformation change of rhodopsin, coupling of rhodopsin to G(t), and PDE activity were each measured separately. RESULTS: The ability of rhodopsin to form the active metarhodopsin II conformation and bind G(t) were both compromised in membranes with reduced levels of n-3 polyunsaturated acyl chains. The activity of PDE, directly related to the integrated cellular response, was reduced in all membranes lacking or deficient in n-3 polyunsaturated acyl chains. PDE activity in membranes containing 22:5n-6 PC was 50% lower than in membranes containing either 22:6n-3 PC or 22:5n-3 PC. CONCLUSIONS: The earliest events in G-protein-coupled signaling; receptor conformation change, receptor-G-protein binding, and PDE activity are reduced in membranes lacking n-3 polyunsaturated acyl chains. Efficient and rapid propagation of G-protein-coupled signaling requires polyunsaturated n-3 phospholipid acyl chains.


Milowska, K., T. Gabryelak, et al. (2003). "Biological activity of pentachlorophenol on the digestive gland cells of the freshwater mussel Unio tumidus." Z Naturforsch [C] 58(11-12): 867-72.

            Many chlorinated phenols and their derivatives are used extensively as insecticides, fungicides and herbicides by industrial and agricultural users throughout the world. Among these substances, pentachlorophenol (PCP) is a broad-spectrum biocide, which is still used as a wood preservative. In this paper, the digestive gland cells were used to assess the effect of PCP in the range of concentrations 3.75-75 microM (0.01-0.2 ppm) on oxidative DNA damage, fluidity changes and peroxidation activity in the plasma membrane. The toxic property of PCP on DNA strand breakage was studied using the comet assay. The results showed that pentachlorophenol in the range of 37.5-75 microM contributed to these lesions. To demonstrate the changes in the fluidity of plasma membrane we used the spectrofluorimetric method using two fluorescence probes: 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) and 12-(9-anthroyloxy) stearic acid (12-AS). It was shown that PC did not influence the surface of plasma membrane but contributed to the increase in the fluidity of the internal region of the lipid bilayer in the range of concentrations 18.75-75 microM (0.05-0.2 ppm).We also examined the effect of PCP on the lipid peroxidation. To imply its peroxidation properties the spectrophotometry method was used to measure the level of malondialdehyde (MDA), one of the endpoints of the peroxidation of polyunsaturated fatty acids. The obtained results showed that PCP in the used doses did not initiate the formation of lipid peroxides. Thus, our investigation indicates that PCP can behave as a prooxidant agent but its action depends on the used doses and parameters chosen for the research.


Miller, R. R., Jr., D. J. Coughlin, et al. (2003). "Ethanol- and Fe(+2)-induced membrane lipid oxidation is not additive in developing chick brains." Comp Biochem Physiol C Toxicol Pharmacol 134(2): 267-79.

            In order to study the effects of exogenous EtOH and/or Fe(+2) on membrane lipid peroxidation, exogenous EtOH, FeCl(2), FeCl(2) & EtOH, NaCl and NaCl & EtOH were injected into fertile chicken eggs. Controls were either shams or injected with saline. These injections were made at 0 days or 0-2 days of development and tissue removed at stage 37 (11 days of development). Embryonic exposure to exogenous EtOH and/or Fe(+2) promoted decreased brain mass, decreased levels of brain membrane polyunsaturated fatty acids, elevated levels of brain lipid hydroperoxides, and elevated levels of Fe(+2) within embryonic brain and liver. These alterations were more severe in triple-injected embryos (E0-2/E11) as compared to single-injected embryos (E0/E11). While exogenous treatments of either EtOH and/or FeCl(2) promoted increased levels of endogenous brain Fe(+2), the effects were not additive. These observations are consistent with the hypothesis that embryonic exposure to exogenous EtOH and/or Fe(+2) promotes brain membrane lipid peroxidation.


Miller, R. R., Jr., B. M. Olson, et al. (2003). "Embryonic exposure to exogenous alpha- and gamma-tocopherol partially attenuates ethanol-induced changes in brain morphology and brain membrane fatty acid composition." Nutr Neurosci 6(4): 201-12.

            Previous studies demonstrated that embryonic exposure to ethanol (EtOH) promoted a reduction in brain mass, a reduction in brain neuron densities, and a reduction in membrane long-chain polyunsaturated fatty acids (PUFAs) in embryonic chick brains. These EtOH-induced reductions in brain membrane PUFAs may be the result of lipid peroxidation because embryonic exposure to exogenous alpha- or gamma-tocopherol partially attenuated EtOH-induced reductions in membrane PUFAs. In this paper, we report that embryonic exposure to exogenous alpha- or gamma-tocopherol attenuated EtOH-induced decreases in endogenous levels of alpha-tocopherol in both embryonic chick brains and liver. Embryonic exposure to exogenous alpha- or gamma-tocopherol also partially attenuated EtOH-induced reductions in brain neuron densities within the cerebral hemispheres of embryonic chick brains. Finally, embryonic exposure to exogenous alpha- or gamma-tocopherol also partially attenuated EtOH-induced reductions in long-chain PUFAs in 2-day old neonatal chick brains.


Mickleborough, T. D., R. L. Murray, et al. (2003). "Fish oil supplementation reduces severity of exercise-induced bronchoconstriction in elite athletes." Am J Respir Crit Care Med 168(10): 1181-9.

            In elite athletes, exercise-induced bronchoconstriction (EIB) may respond to dietary modification, thereby reducing the need for pharmacologic treatment. Ten elite athletes with EIB and 10 elite athletes without EIB (control subjects) participated in a randomized, double-blind crossover study. Subjects entered the study on their normal diet, and then received either fish oil capsules containing 3.2 g eicosapentaenoic acid and 2.2 g docohexaenoic acid (n-3 polyunsaturated fatty acid [PUFA] diet; n = 5) or placebo capsules containing olive oil (placebo diet; n = 5) taken daily for 3 weeks. Diet had no effect on preexercise pulmonary function in either group or on postexercise pulmonary function in control subjects. However, in subjects with EIB, the n-3 PUFA diet improved postexercise pulmonary function compared with the normal and placebo diets. FEV1 decreased by 3 +/- 2% on n-3 PUFA diet, 14.5 +/- 5% on placebo diet, and 17.3 +/- 6% on normal diet at 15 minutes postexercise. Leukotriene (LT)E4, 9alpha, 11beta-prostaglandin F2, LTB4, tumor necrosis factor-alpha, and interleukin-1beta, all significantly decreased on the n-3 PUFA diet compared with normal and placebo diets and after the exercise challenge. These data suggest that dietary fish oil supplementation has a markedly protective effect in suppressing EIB in elite athletes, and this may be attributed to their antiinflammatory properties.


Meyer, B. J., N. J. Mann, et al. (2003). "Dietary intakes and food sources of omega-6 and omega-3 polyunsaturated fatty acids." Lipids 38(4): 391-8.

            Both n-6 and n-3 polyunsaturated fatty acids (PUFA) are recognized as essential nutrients in the human diet, yet reliable data on population intakes are limited. The aim of the present study was to ascertain the dietary intakes and food sources of individual n-6 and n-3 PUFA in the Australian population. An existing database with fatty acid composition data on 1690 foods was updated with newly validated data on 150 foods to estimate the fatty acid content of foods recorded as eaten by 10,851 adults in the 1995 Australian National Nutrition Survey. Average daily intakes of linoleic (LA), arachidonic (AA), alpha-linolenic (LNA), eicosapentaenoic (EPA), docosapentaenoic (DPA), and docosahexaenoic (DHA) acids were 10.8, 0.052, 1.17, 0.056, 0.026, and 0.106 g, respectively, with long-chain (LC) n-3 PUFA (addition of EPA, DPA, and DHA) totaling 0.189 g; median intakes were considerably lower (9.0 g LA, 0.024 g AA, 0.95 g LNA, 0.008 g EPA, 0.006 g DPA, 0.015 g DHA, and 0.029 g LC n-3 PUFA). Fats and oils, meat and poultry, cereal-based products and cereals, vegetables, and nuts and seeds were important sources of n-6 PUFA, while cereal-based products, fats and oils, meat and poultry, cereals, milk products, and vegetable products were sources of LNA. As expected, seafood was the main source of LC n-3 PUFA, contributing 71%, while meat and eggs contributed 20 and 6%, respectively. The results indicate that the majority of Australians are failing to meet intake recommendations for LC n-3 PUFA (> 0.2 g per day) and emphasize the need for strategies to increase the availability and consumption of n-3-containing foods.


Meyer, A., P. Cirpus, et al. (2003). "Biosynthesis of docosahexaenoic acid in Euglena gracilis: biochemical and molecular evidence for the involvement of a Delta4-fatty acyl group desaturase." Biochemistry 42(32): 9779-88.

            Docosahexaenoic acid (DHA) can be synthesized via alternative routes from which only the omega3/omega6-pathways involve the action of a Delta4-fatty acid desaturase. We examined the suitability of Euglena gracilis, Thraustochytrium sp., Schizochytrium sp., and Crypthecodinium cohnii to serve as sources for cloning a cDNA encoding a Delta4-fatty acid desaturase. For this purpose we carried out in vivo labeling studies with radiolabeled C22 polyunsaturated fatty acid substrates. Schizochytrium sp. was unable to convert exogenously supplied [2-(14)C]-docosapentaenoic acid (DPA, 22:5(Delta)(7,10,13,16,19)) to DHA, while E. gracilis and Thraustochytrium sp. carried out this desaturation very efficiently. Hydrogenation and alpha-oxidation of the labeled DHA isolated from these two organisms showed that it was the result of direct Delta4-desaturation and not of substrate breakdown and resynthesis. To clone the desaturase gene, a cDNA library of E. gracilis was subjected to mass sequencing. A full-length clone with highest homology to the Delta4-desaturase of Thraustochytrium sp. was isolated, and its function was verified by heterologous expression in yeast. The desaturase efficiently converted DPA to DHA. Analysis of the substrate specificity demonstrated that the enzyme activity was not limited to C22 fatty acids, since it also efficiently desaturated C16 fatty acids. The enzyme showed strict Delta4-regioselectivity and required the presence of a Delta7-double bond in the substrate. Positional analysis of phosphatidylcholine revealed that the proportion of the Delta4-desaturated products was up to 20 times higher in the sn-2 position than in the sn-1 position.


Meydani, M. (2003). "Soluble adhesion molecules: surrogate markers of cardiovascular disease?" Nutr Rev 61(2): 63-8.

            Expression of adhesion molecules on the surface of endothelial and immune cells is important for the interaction between immune and endothelial cells during the inflammatory process. Several of these adhesion molecules have been identified and are believed to be important in the pathogenesis of atherosclerosis. The soluble forms of adhesion molecules are shed from cell surfaces and released into blood circulation; their measurement may have use as markers in predicting cardiovascular disease. Experimental and some clinical data have indicated that reducing expression of some adhesion molecules is another mechanism by which dietary fats such as n-3 polyunsaturated fatty acids and oleic acid, as well as vitamin E and other antioxidants found in fruits and vegetables, may lower the risk of cardiovascular disease.


Metz, T. O., N. L. Alderson, et al. (2003). "Pyridoxamine traps intermediates in lipid peroxidation reactions in vivo: evidence on the role of lipids in chemical modification of protein and development of diabetic complications." J Biol Chem 278(43): 42012-9.

            Maillard or browning reactions between reducing sugars and protein lead to formation of advanced glycation end products (AGEs) and are thought to contribute to the pathogenesis of diabetic complications. AGE inhibitors such as aminoguanidine and pyridoxamine (PM) inhibit both the formation of AGEs and development of complications in animal models of diabetes. PM also inhibits the chemical modification of protein by advanced lipoxidation end products (ALEs) during lipid peroxidation reactions in vitro. We show here that several PM adducts, formed in incubations of PM with linoleate and arachidonate in vitro, are also excreted in the urine of PM-treated animals. The PM adducts N-nonanedioyl-PM (derived from linoleate), N-pentanedioyl-PM, N-pyrrolo-PM, and N-(2-formyl)-pyrrolo-PM (derived from arachidonate), and N-formyl-PM and N-hexanoyl-PM (derived from both fatty acids) were quantified by liquid chromatography-mass spectrometry analysis of rat urine. Levels of these adducts were increased 5-10-fold in the urine of PM-treated diabetic and hyperlipidemic rats, compared with control animals. We conclude that the PM functions, at least in part, by trapping intermediates in AGE/ALE formation and propose a mechanism for PM inhibition of AGE/ALE formation involving cleavage of alpha-dicarbonyl intermediates in glycoxidation and lipoxidation reactions. We also conclude that ALEs derived from polyunsaturated fatty acids are increased in diabetes and hyperlipidemia and may contribute to development of long term renal and vascular pathology in these diseases.


Metcalf, R. G., M. J. James, et al. (2003). "A practical approach to increasing intakes of n-3 polyunsaturated fatty acids: use of novel foods enriched with n-3 fats." Eur J Clin Nutr 57(12): 1605-12.

            OBJECTIVES: To assess the effects of providing a wide range of foodstuffs containing n-3 polyunsaturated fatty acids (PUFA), occurring naturally or from fortification, on intake and blood and tissue proportions of n-3 PUFA. DESIGN: Before/after dietary intervention study. SETTING: Adelaide, Australia. SUBJECTS: 16 healthy males recruited from the community. INTERVENTIONS: Subjects were provided with a range of foodstuffs naturally containing n-3 PUFA (fresh fish, canned fish, flaxseed meal, canola oil) and items fortified with fish oil (margarine spread, milk, sausages, luncheon meat, french onion dip). Food choices were left to the discretion of each subject. Intake was estimated by diet diary. Blood was collected at-2, 0, 2, and 4 weeks for fatty acid analysis. MAIN OUTCOME MEASURES: Dietary intakes; plasma, platelet, and mononuclear cell phospholipid fatty acids. RESULTS: Consumption of n-3 PUFA increased significantly: alpha-linolenic acid (ALA) from 1.4 to 4.1 g/day (P<0.001), eicosapentaenoic acid (EPA) from 0.03 to 0.51 g/day (P<0.001), and docosahexaenoic acid (DHA) from 0.09 to 1.01 g/day (P<0.001). Linoleic acid (LA) intake decreased from 13.1 to 9.2 g/day (P<0.001). The proportions of EPA and DHA increased significantly in all phospholipid pools examined; plasma EPA from 1.13% of total fatty acids to 3.38% (P<0.001) and DHA from 3.76 to 7.23% (P<0.001); mononuclear cell EPA from 0.40 to 1.25% (P<0.001) and DHA from 2.33 to 4.08% (P<0.001); platelet EPA from 0.41 to 1.2% (P<0.001) and DHA from 1.64 to 3.07% (P<0.001). CONCLUSION: Incorporating fish oil into a range of novel commercial foods provides the opportunity for wider public consumption of n-3 PUFA with their associated health benefits. SPONSORSHIP: Dawes Scholarship, Royal Adelaide Hospital.


Merzouk, H. and N. A. Khan (2003). "Implication of lipids in macrosomia of diabetic pregnancy: can n-3 polyunsaturated fatty acids exert beneficial effects?" Clin Sci (Lond) 105(5): 519-29.

            Macrosomia or fetal obesity is a frequent complication of pregnancy in diabetes mellitus. Several alterations observed in carbohydrate and lipid metabolism in macrosomic infants of diabetic mothers are thought to be a consequence of maternal hyperglycaemia leading to fetal hyperinsulinaemia. Macrosomic infants of diabetic mothers are prone to the development of glucose intolerance, obesity and diabetes during childhood and adulthood. Furthermore, increasing evidence is accumulating regarding the importance of n -3 polyunsaturated fatty acids (PUFAs) in the reduction of plasma lipids and hyperglycaemia. In this review article, we shed light on the abnormalities in lipid metabolism in macrosomia. We also raise the question of the possible beneficial effects of n -3 PUFAs in diabetic pregnancy and in the prevention and treatment of long-term metabolic abnormalities associated with macrosomia.


Merritt, R. J., N. Auestad, et al. (2003). "Safety evaluation of sources of docosahexaenoic acid and arachidonic acid for use in infant formulas in newborn piglets." Food Chem Toxicol 41(6): 897-904.

            Human milk provides small quantities of preformed docosahexaenoic acid (DHA) and arachidonic acid (ARA), usually less than 1% of total fatty acids. Vegetable oil blends commonly used in infant formulas have, until recently, provided the essential fatty acid precursors for these long-chain polyunsaturated fatty acids (LCPUFA), but no preformed DHA and ARA. This study evaluated the safety of ingredient sources of DHA and ARA for use in infant formulas in a neonatal piglet model. Newborn piglets were allowed to suckle for 3 days and then divided into 4 feeding groups of 6 males and 6 females. Piglets were bottle-fed at frequent feeding intervals until 19 days of age. The composition of the piglet formulas was modeled after standard milk-based formulas for human infants while meeting nutritional requirements for piglets. Formulas were a control formula (no added DHA or ARA), a DHA formula providing 55 mg DHA/100 Cal, an ARA formula providing 96 mg/100 Cal ARA, and a DHA+ARA formula providing 34 mg DHA and 62 mg ARA/100 Cal. All formulas were equal in fat content and provided approximately 1000 Cal/l. The ARA-rich oil was from a fermentation product of Mortierella alpina (40 wt.% fatty acids as ARA) and DHA was from high DHA tuna oil (25 wt.% fatty acids as DHA). There were no test article related effects of DHA and/or ARA indicative of an adverse health consequence to the animals seen in the clinical signs, body weights, food consumption, clinical chemistry, hematology, organ weights or gross or histopathology. The findings in this neonatal animal study support the safety of these ingredient oil sources of DHA and ARA for use in infant formulas.


Merendino, R. A., F. Salvo, et al. (2003). "Malondialdehyde in benign prostate hypertrophy: a useful marker?" Mediators Inflamm 12(2): 127-8.

            Benign prostate hypertrophy (BPH) is the most common benign tumor in men due to obstruction of the urethra and, finally, uremia. Malondialdehyde (MDA) is a product derived from peroxidation of polyunsaturated fatty acids and related esters. Evaluation of MDA in serum represents a non-invasive biomarker of oxidative stress. Prostate-specific antigen (PSA) is a sensitive marker for prostatic hypertrophy and cancer. We analyzed MDA serum levels to evaluate the oxidative stress in BPH. To this end, 22 BPH patients and 22 healthy donors were enrolled. Data show an increase of MDA level in BPH patients and a positive correlation between PSA and MDA levels. In conclusion, we describe a previously unknown relationship between PSA and MDA as an index of inflammation and oxidative stress in BPH.


McGinley, C. M. and W. A. van der Donk (2003). "Enzymatic hydrogen atom abstraction from polyunsaturated fatty acids." Chem Commun (Camb)(23): 2843-6.

            The oxidation of polyunsaturated fatty acids such as arachidonic and linoleic acid initiates a plethora of cell signaling pathways in animals and plants. The chemistry of the enzymatic oxidation has been investigated for several enzymes, most notably prostaglandin synthase and the lipoxygenases, revealing many surprises and impressive examples of enzymatic control of hydrogen atom abstraction and subsequent oxygenation.


Mattos, R., A. Guzeloglu, et al. (2003). "Polyunsaturated fatty acids and bovine interferon-tau modify phorbol ester-induced secretion of prostaglandin F2 alpha and expression of prostaglandin endoperoxide synthase-2 and phospholipase-A2 in bovine endometrial cells." Biol Reprod 69(3): 780-7.

            Embryonic mortality in cattle may occur because of inadequate inhibition of uterine secretion of prostaglandin (PG) F2alpha mediated by bovine interferon-tau (bIFN-tau). The objectives of the present study were to determine whether polyunsaturated fatty acids inhibit secretion of PGF2alpha from bovine endometrial cells induced by stimulating protein kinase C with phorbol 12,13 dibutyrate (PDBu) and to investigate possible mechanisms of action. Confluent cells were exposed for 24 h to 100 microM of linoleic, arachidonic (AA; C20:4, n-6), linolenic (LNA; C18:3, n-3), eicosapentaenoic (EPA; C20:5, n-3), or docosahexaenoic (DHA; C22:6, n-3) acid. After incubation, cells were washed and stimulated with PDBu. The EPA, DHA, and LNA attenuated secretion of PGF2alpha in response to PDBu. The EPA and DHA were more potent inhibitors than LNA. The EPA inhibited secretion of PGF2alpha at 6.25 microM. Secretion of PGF2alpha in response to PDBu decreased with increasing incubation time with EPA. Both bIFN-tau and EPA inhibited secretion of PGF2alpha, and their inhibitory effects were additive. The bIFN-tau, but not EPA, reduced the abundance of PG endoperoxide synthase-2 (PGHS-2) mRNA. Incubation with 100 microM EPA, DHA, or AA for 24 h followed by treatment with PDBu did not affect concentrations of PGHS-2 and phospholipase A2 proteins. The EPA and DHA inhibit secretion of PGF2alpha through a mechanism different from that of bIFN-tau. The effect of EPA on PGF2alpha secretion may be caused by competition with AA for PGHS-2 activity or reduction of PGHS-2 activity. The use of EPA and DHA to inhibit uterine secretion of PGF2alpha and to improve embryonic survival in cattle warrants further investigation.


Matias, I., M. Leonhardt, et al. (2003). "Effect of maternal under-nutrition on pup body weight and hypothalamic endocannabinoid levels." Cell Mol Life Sci 60(2): 382-9.

            Dietary long-chain polyunsaturated fatty acids are known to influence brain levels of the endocannabinoid anandamide in newborn pigs and mice. Furthermore, endocannabinoids were shown to control pup suckling and body weight in mice, and food intake in adult rodents. Here we determined the effect of maternal under-nutrition during gestation, lactation, or both, on body weight, and on the levels of endocannabinoids and expression of cannabinoid CB1 receptors and fatty acid amide hydrolase in the hypothalamus of rat pups at weaning (21 days old) or adult rats (4 months old). Maternal under-nutrition resulted in a striking decrease in body weight of weaning rats, paralleled by a decrease in the hypothalamic levels of the endocannabinoid anandamide, but not of 2-arachidonoylglycerol. No significant change in the hypothalamic expression of either cannabinoid CB1 receptors or fatty acid amide hydrolase mRNA was detected in any of the three groups of weaned pups. The decrease in pup body weight and hypothalamic anandamide levels was not observable in 4-month-old rats from any of the three groups. These data suggest that maternal under-nutrition causes a decrease in hypothalamic anandamide levels and loss of body weight, and confirm a crucial role for endocannabinoid signalling in neonatal development.


Mateo, R., W. N. Beyer, et al. (2003). "Relation of fatty acid composition in lead-exposed mallards to fat mobilization, lipid peroxidation and alkaline phosphatase activity." Comp Biochem Physiol C Toxicol Pharmacol 135(4): 451-8.

            The increase of n-6 polyunsaturated fatty acids (PUFA) in animal tissues has been proposed as a mechanism of lead (Pb) poisoning through lipid peroxidation or altered eicosanoids metabolism. We have studied fatty acid (FA) composition in liver and brain of mallards (Anas platyrhynchos) feeding for 3 weeks on diets containing combinations of low or high levels of vitamin E (20 or 200 UI/kg) and Pb (0 or 2 g/kg). Saturated FA, n-6 PUFA and total concentrations of FA were higher in livers of Pb-exposed mallards, but not in their brains. The percentage of n-6 PUFA in liver and brain was slightly higher in Pb-exposed mallards. The increase of n-6 PUFA in liver was associated with decreased triglycerides and increased cholesterol in plasma, thus could be in part attributed to feed refusal and fat mobilization. The hepatic ratios between adrenic acid (22:4 n-6) and arachidonic acid (20:4 n-6) or between adrenic acid and linoleic acid (18:2 n-6) were higher in Pb exposed birds, supporting the existing hypothesis of increased fatty acid elongation by Pb. Among the possible consequences of increased n-6 PUFA concentration in tissues, we found increased lipid peroxidation in liver without important histopathological changes, and decreased plasma alkaline phosphatase activity that may reflect altered bone metabolism in birds.


Massiera, F., P. Saint-Marc, et al. (2003). "Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern?" J Lipid Res 44(2): 271-9.

            High fat intake is associated with fat mass gain through fatty acid activation of peroxisome proliferator-activated receptors delta and gamma, which promote adipogenesis. We show herein that, compared to a combination of specific agonists to both receptors or to saturated, monounsaturated, and omega-3 polyunsaturated fatty acids, arachidonic acid (C20:4, omega-6) promoted substantially the differentiation of clonal preadipocytes. This effect was blocked by cyclooxygenase inhibitors and mimicked by carbacyclin, suggesting a role for the prostacyclin receptor and activation of the cyclic AMP-dependent pathways that regulate the expression of the CCAAT enhancer binding proteins beta and delta implicated in adipogenesis. During the pregnancy-lactation period, mother mice were fed either a high-fat diet rich in linoleic acid, a precursor of arachidonic acid (LO diet), or the same isocaloric diet enriched in linoleic acid and alpha-linolenic acid (LO/LL diet). Body weight from weaning onwards, fat mass, epididymal fat pad weight, and adipocyte size at 8 weeks of age were higher with LO diet than with LO/LL diet. In contrast, prostacyclin receptor-deficient mice fed either diet were similar in this respect, indicating that the prostacyclin signaling contributes to adipose tissue development. These results raise the issue of the high content of linoleic acid of i) ingested lipids during pregnancy and lactation, and ii) formula milk and infant foods in relation to the epidemic of childhood obesity.


Marchese, C., V. Maresca, et al. (2003). "UVB-induced activation and internalization of keratinocyte growth factor receptor." Oncogene 22(16): 2422-31.

            Ultraviolet irradiation of mammalian cells induces several events that include activation of growth factor receptors and triggering of signal transduction pathway. Most of the UV responses are mediated by the production of reactive oxygen species (ROS) and can be blocked by antioxidants. In this study, we analysed the effect of UVB irradiation at physiologic doses and that of the pro-oxidant agent cumene hydroperoxide (CUH) on the activation of the receptor for keratinocyte growth factor (KGF), a key mediator of epithelial growth and differentiation. Exposure to both UVB (30-150 mJ/cm(2)) and CUH (200 microM of NIH3T3 KGFR (KGF receptors) transfectants caused a rapid tyrosine phosphorylation and activation of KGFR similar to that induced by KGF, and internalization of the activated receptor. The KGFR expression appeared unmodified by the treatments. Ultrastructural observations of both UVB- and CUH-treated cells showed a normal morphology of the plasma membranes and intracellular organelles. The antioxidant N-acetylcysteine inhibited UVB-induced receptor phosphorylation. The generation of an intracellular oxidative stress was detected as a decrease of catalase activity and of vitamin E, and reduced glutathione levels, whereas superoxide dismutase activity was not significantly modified. A peroxidation of polyunsaturated fatty acids of cell membranes was observed after both treatments, associated with the intracellular oxidative stress. Similar biochemical events were observed on NIH3T3 untransfected control cells, suggesting that KGFR activation follows intracellular generation of ROS and is not associated with a scavenging effect. Taken together our results demonstrate that exposure to UVB and to oxidant stimuli induces a rapid intracellular production of ROS, which in turn are capable of triggering KGFR activation and internalization, similar to those induced by KGF.


Malerod, L., M. Sporstol, et al. (2003). "Hepatic scavenger receptor class B, type I is stimulated by peroxisome proliferator-activated receptor gamma and hepatocyte nuclear factor 4alpha." Biochem Biophys Res Commun 305(3): 557-65.

            Excessive cellular cholesterol is transported to the liver by a pathway called 'reverse cholesterol transport.' Scavenger receptor class B, type I (SR-BI) mediates cholesterol uptake in the liver. Polyunsaturated fatty acids, known to activate peroxisome proliferator-activated receptor (PPAR), have been reported to increase hepatic cholesterol uptake. We found in the present study that PPARgamma induces expression of SR-BI in rat hepatocytes, liver endothelial cells, and Kupffer cells. In contrast, PPARalpha increased SR-BI levels only in hepatocytes and liver endothelial cells. PPARgamma/RXR binds to a response element between -459 and -472 bp in the human SR-BI promoter. Furthermore, hepatocyte nuclear factor 4alpha (HNF4alpha) was found to enhance PPARgamma-mediated SR-BI transcription. Thiazolidinedione (TZD)-activated PPARgamma/RXR increased hepatic SR-BI levels, which may lead to increased hepatic cholesterol uptake and less accumulation of lipids in peripheral tissues. The present results are in agreement with previous reports, indicating that specific PPARgamma-agonists (such as TZDs) protect against atherosclerosis.


Maldonado, E. N., Y. Chico, et al. (2003). "Influence of the fatty acid composition of lipids in chylomicron remnants derived from fish or corn oil on the lipid profile of cultured rat hepatocytes." J Physiol Biochem 59(2): 85-100.

            The aim of this work was to characterise the lipid and fatty acid composition of chylomicron remnants enriched in n-3 or n-6 polyunsaturated fatty acids (PUFA) and to investigate their influence on the fatty acid profiles of the lipids of rat hepatocytes cultured in monolayers. Chylomicrons were prepared from the lymph collected from the thoracic duct of rats given an oral dose of fish or corn oil (high in n-3 and n-6 PUFA, respectively), and remnants were prepared in vitro from such chylomicrons using rat plasma containing lipoprotein lipase. The fatty acids predominating in the oils abounded also in their respective chylomicrons and remnants, especially in triacylglycerols. Chylomicrons as well as remnants contained small amounts of phospholipids and long-chain PUFA that were minor in, or absent from, the dietary oils, evidently provided by the intestinal epithelium. The incubation of hepatocytes for 6 h, with either n-3 or n-6 PUFA-rich remnants (0.25-0.75 mM triacylglycerol) resulted in a dose-dependent increase in the amount of triacylglycerols and phospholipids in the cells, which was not affected further by increasing the incubation time to 19 h. Whereas hepatocyte triacylglycerols mostly incorporated the PUFA predominating in each remnant type, the fatty acid profile of cell phospholipids was virtually unchanged. In addition, irrespective of whether they were enriched in n-3 or n-6 PUFA, remnants promoted a relative decrease in the amount of cholesteryl esters, a minor hepatocyte lipid class poor in PUFA. The results demonstrate that the hepatocyte fatty acid profile is modulated in a lipid-class specific way by the amount and type of dietary PUFA delivered to cells in chylomicron remnants.


Malcolm, C. A., R. Hamilton, et al. (2003). "Scotopic electroretinogram in term infants born of mothers supplemented with docosahexaenoic acid during pregnancy." Invest Ophthalmol Vis Sci 44(8): 3685-91.

            PURPOSE: To test the hypothesis that the supplementation of the diets of pregnant women with a fish oil rich in docosahexaenoic acid (DHA) enhances retinal development in their healthy term infants, as measured during the early postnatal period by the electroretinogram (ERG). METHODS: One hundred pregnant women were randomized to receive either a fish oil (n = 50) or a placebo oleic acid dietary supplement (n = 50) from 15 weeks of pregnancy until delivery. Total fatty acids in red blood cells (RBCs) and plasma were measured in mothers at 15 and 28 weeks of pregnancy and at delivery and in their infants in umbilical cord blood. Infant retinal development was assessed within the first week of life with full-field ERGs that included a scotopic blue intensity series (n = 41) and a bright white flash (2.0 log cd-s/m(2); n = 44). RESULTS: Infants born of mothers who received supplements did not differ at birth in weight, gestational age, or any other standard variable. Infant DHA status at birth, as measured from umbilical cord blood, did not differ significantly between maternal supplementation groups. ERG implicit times, amplitudes, and parameters of the stimulus-response function did not differ significantly between infants in the maternal supplemented and placebo groups. There was, however, a relationship between infant DHA status and maturity of the retina at birth, regardless of maternal supplementation group. A measure of retinal sensitivity (log sigma) correlated significantly (P < 0.005) with DHA status (as a percentage of total fatty acid; TFA) in infant cord blood. Infants in the highest quartile for cord blood DHA had higher retinal sensitivity compared with infants in the lowest quartile. Infants in the highest quartile for plasma DHA, both as a percentage of TFA and concentration, were born at a significantly later gestational age than were infants in the lower quartiles. CONCLUSIONS: These findings demonstrate an association between the DHA status of term infants and retinal sensitivity, suggesting an essential role of this long-chain polyunsaturated fatty acid (LCPUFA) in the development and function of the retina. However, maternal DHA status was not significantly associated with infant retinal sensitivity and no direct effect of maternal supplementation was observed.


Madsen, T., J. H. Christensen, et al. (2003). "The effect of dietary n-3 fatty acids on serum concentrations of C-reactive protein: a dose-response study." Br J Nutr 89(4): 517-22.

            C-reactive protein (CRP) is a sensitive marker for low-grade inflammation. Long-chain n-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory effects. The objective of the present study was to investigate the effect on serum levels of CRP of n-3 PUFA at two different doses. We also investigated correlations between CRP and the cellular contents of PUFA. Sixty healthy volunteers (twenty-five women and thirty-five men) were randomly assigned to three treatment groups in a double-blind design. The subjects received a supplement of either 6.6 g n-3 PUFA/d, 2.0 g n-3 PUFA/d or placebo (olive oil) for 12 weeks. CRP was measured using a highly sensitive assay. The median serum CRP concentration was 0.78 mg/l. No significant correlations were found between CRP and the content of n-3 PUFA in granulocytes or platelets. Subjects receiving n-3 PUFA had a significant (P<0.01) increase in the cellular contents of 20 : 5n-3, 22 : 5n-3 and 22 : 6n-3, with the largest increase occurring in the group receiving 6.6 g PUFA/d. A significant (P<0.01) decrease in cellular content of 18 : 2n-6 and 20 : 4n-6 was observed simultaneously. Serum CRP concentrations, however, were unaffected by the PUFA-containing supplements. The present study shows that dietary supplementation with PUFA-containing supplements has no effect on serum concentrations of CRP, measured with a highly sensitive assay, in healthy subjects.


Maccarrone, M. and A. Finazzi-Agro (2003). "The endocannabinoid system, anandamide and the regulation of mammalian cell apoptosis." Cell Death Differ 10(9): 946-55.

            Endocannabinoids are a new class of lipid mediators, which include amides, esters and ethers of long-chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the main endogenous agonists of cannabinoid receptors able to mimic several pharmacological effects of Delta-9-tetrahydrocannabinol, the active principle of Cannabis sativa preparations like hashish and marijuana. The pathways leading to the synthesis and release of AEA and 2-AG from neuronal and non-neuronal cells are still rather uncertain. Instead, it is known that the activity of AEA is limited by cellular uptake through a specific membrane transporter, followed by intracellular degradation by a fatty acid amide hydrolase. Together with AEA and congeners these proteins form the 'endocannabinoid system'. Here, the involvement of AEA in apoptosis and the underlying signal transduction pathways will be reviewed, along with the metabolic routes and the molecular targets of this endocannabinoid. Also, recent findings on the apoptotic potential of AEA for neuronal cell differentiation and brain development will be discussed.


Luczaj, W. and E. Skrzydlewska (2003). "DNA damage caused by lipid peroxidation products." Cell Mol Biol Lett 8(2): 391-413.

            Lipid peroxidation is a process involving the oxidation of polyunsaturated fatty acids (PUFAs), which are basic components of biological membranes. Reactive electrophilic compounds are formed during lipid peroxidation, mainly alpha, beta-unsaturated aldehydes. These compounds yield a number of adducts with DNA. Among them, propeno and substituted propano adducts of deoxyguanosine with malondialdehyde (MDA), acrolein, crotonaldehyde and etheno adducts, resulting from the reactions of DNA bases with epoxy aldehydes, are a very important group of adducts. The epoxy aldehydes are more reactive towards DNA than the parent unsaturated aldehydes. The compounds resulting from lipid peroxidation mostly react with DNA showing both genotoxic and mutagenic action; among them, 4-hydroxynonenal is the most genotoxic, while MDA is the most mutagenic. DNA damage caused by the adducts of lipid peroxidation products with DNA can be removed by the repairing action of glycosylases. The formed adducts have been hitherto analyzed using the IPPA (Imunopurification-(32)P-postlabelling assay) method and via gas chromatography/electron capture negtive chemical ionization/mass spectrometry (GC/EC NCI/MS). A combination of liquid chromatography with electrospray tandem mass spectrometry (LC/ES-MSMS) with labelled inner standard has mainly been used in recent years.


Lu, Z. H., Y. M. Mu, et al. (2003). "Saturated free fatty acids, palmitic acid and stearic acid, induce apoptosis by stimulation of ceramide generation in rat testicular Leydig cell." Biochem Biophys Res Commun 303(4): 1002-7.

            In men, obesity has generally been associated with reduced plasma testosterone levels and with elevation of the plasma free fatty acids (FFAs). In this study, we investigated the effects of saturated FFAs including palmitic acid (PA) and stearic acid (SA), and polyunsaturated FFA arachidonic acid (AA) on the survival of rat testicular Leydig cell cultured in vitro. PA and SA markedly suppressed Leydig cell survival in a time- and dose-dependent manner. In contrast, AA stimulated the cell proliferation at 5-10 times of physiological concentration. The suppressive effect of PA and SA on cell survival was caused by apoptosis evidenced by DNA ladder formation and Annexin V-EGFP/propidium iodide staining of the cells. The apoptotic effect of PA was possibly mediated by ceramide generation because it could be completely blocked by ceramide synthase inhibitor fumonisin B1 and exogenous ceramide itself could directly induce apoptosis in vitro. Surprisingly, the apoptosis induced by PA could be partly prevented by AA. These results indicate that PA and SA induce apoptosis in testicular Leydig cells by ceramide production and these apoptotic effects may be a possible mechanism for reproductive abnormalities in obese men, and AA can partly prevent the apoptotic effect induced by saturated FFA.


Lopez-Bote, C. J., B. Isabel, et al. (2003). "Effect of vitamin E supplementation and partial substitution of poly- with mono-unsaturated fatty acids in pig diets on muscle, and microsome extract alpha-tocopherol concentration and lipid oxidation." Arch Tierernahr 57(1): 11-25.

            The experiment was organized in a 3 x 2 factorial arrangement with three dietary fat blends and a basal (20 mg kg(-1) diet) or supplemented (220 mg kg(-1)) level of alpha-tocopheryl acetate. Dietary vitamin E and monounsaturated to polyunsaturated fatty acid ratio (dietary MUFA/PUFA) affected muscle alpha-tocopherol concentration (alpha-tocopherol [log microg g(-1)] = 0.18 (+/- 0.105) + 0.0034 (+/- 0.0003) x dietary alpha-tocopherol [mg kg(-1) diet] (P < 0.0001) + 0.39 (+/- 0.122) x dietary MUFA/PUFA (P < 0.0036)). An interaction between dietary alpha-tocopherol and dietary MUFA/PUFA exists for microsome alpha-tocopherol concentration (alpha-tocopherol [log microg g(-1)] = 1.14 ( +/- 0.169) (P < 0.0001) + 0.0056 ( +/- 0.00099) x dietary alpha-tocopherol [mg kg(-1) diet] (P <0.0001) + 0.54 (+/- 0.206) x dietary MUFA/PUFA (P < 0.0131) - 0.0033 (+/- 0.0011) x dietary alpha-tocopherol [mg kg(-1))] x dietary MUFA/PUFA (P < 0.0067)), and hexanal concentration in meat (hexanal [ng x g(-1)] = 14807.9 (+/- 1489.8)- 28.8 (+/- 10.6) dietary alpha-tocopherol [mg x kg(-1)] (P < 0.01) - 8436.6 (+/- 1701.6) x dietary MUFA/PUFA (P < 0.001) + 24.0 (+/- 11.22) x dietary alpha-tocopherol-dietary MUFA/ PUFA (P < 0.0416)). It is concluded that partial substitution of dietary PUFA with MUFA lead to an increase in the concentration of alpha-tocopherol in muscle and microsome extracts. An interaction between dietary alpha-tocopherol and fatty acids exists, in which at low level of dietary vitamin E inclusion, a low MUFA/ PUFA ratio leads to a reduction in the concentration of alpha-tocopherol in microsome extracts and a concentration of hexanal in meat above the expected values.


Long, J. A. and M. Kramer (2003). "Effect of vitamin E on lipid peroxidation and fertility after artificial insemination with liquid-stored turkey semen." Poult Sci 82(11): 1802-7.

            Turkey sperm plasma membranes contain high levels of polyunsaturated fatty acids that are susceptible to lipid peroxidation during in vitro storage at 4 degrees C. Herein we assessed the degree of lipid peroxidation and fertility potential of semen liquid-stored for 24 h with the antioxidant vitamin E. Semen was collected weekly from 44 males and pooled as pairs (total = 22); the individuals in paired samples exhibited similar semen quality parameters. After initial semen evaluation, pooled samples were extended with Beltsville Poultry Semen Extender containing no supplement (control) or 10 or 40 microg/mL vitamin E and then stored at 4 degrees C with constant aeration for 24 h. Lipid peroxidation was determined by measuring malonaldehyde (MDA) in aliquots (50 x 10(6) sperm) of fresh (0 h) and stored (24 h) semen. Sperm mobility was also evaluated. A total of 176 hens (8 hens/tom pair; 4 hens/0 h, 4 hens/24 h) were inseminated (150 x 10(6) sperm) weekly for 6 wk, and fertility was determined after 7 d of incubation. Initial MDA values of the 22 tom pairs ranged from 0.928 to 1.36 uM. Males varied in production of MDA during in vitro storage, with most pairs exhibiting a threefold increase. Results indicated that supplemental vitamin E did not reduce lipid peroxidation during liquid storage. Not surprisingly, artificial insemination with stored semen (with much higher MDA values) yielded lower fertility rates than control regardless of the presence of vitamin E. These results demonstrate that lipid peroxidation is a significant factor affecting the fertility of stored turkey sperm and that methods to prevent or reduce lipid peroxidation remain to be elucidated.


Linseisen, J., M. B. Schulze, et al. (2003). "Quantity and quality of dietary fat, carbohydrate, and fiber intake in the German EPIC cohorts." Ann Nutr Metab 47(1): 37-46.

            AIM: This evaluation aims to describe the quantity and quality of dietary fat, carbohydrate and fiber intake in both German cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Estimates are based on standardized computer-guided 24-hour dietary recalls from 1,078 women and 1,013 men in Heidelberg and 898 women and 1,032 men in Potsdam. In a subsample, plasma phospholipid (PL) fatty acids were analyzed as well. RESULTS: Adjusted mean dietary intake estimates demonstrated that the contribution of fat as well as n-6 and n-3 polyunsaturated fatty acids (PUFA) to the total daily energy intake was higher in both women and men of EPIC-Potsdam compared to EPIC-Heidelberg. Surprisingly, the dietary n-6/n-3 PUFA ratio was lower in the Potsdam cohort. These results were confirmed by means of the PL fatty acid pattern. Besides the higher contribution of polysaccharides to total energy intake in EPIC-Heidelberg, women of the Heidelberg cohort revealed a significantly lower contribution of mono- and disaccharides (sucrose) to total energy intake. Although total fiber intake data were similar in both cohorts, analysis by food groups showed differences in dietary fiber intake originating from the food groups cereals, fruits and potatoes. CONCLUSION: The results demonstrate distinct differences in the dietary fat, carbohydrate and fiber intake between both German EPIC cohorts, which contribute to the exposure variation in the whole of EPIC.


Ling, T. Y., Y. H. Huang, et al. (2003). "Fatty acids modulate transforming growth factor-beta activity and plasma clearance." Faseb J 17(11): 1559-61.

            The activity and plasma clearance of transforming growth factor (TGF)-beta are known to be regulated by activated alpha2-macroglobulin (alpha2M*). This has been implicated in pathophysiological processes, but no small molecule compounds have been reported to modulate TGF-beta activity by affecting the interaction of TGF-beta and alpha2M*. Here, we demonstrate that fatty acids are capable of inhibiting complex formation of TGF-beta isoforms and alpha2M* as demonstrated by nondenaturing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This is dependent on carbon chain length (C20, C18, C16, C14 > C12 > C10), degree of unsaturation (polyunsaturated > saturated), and TGF-beta isoforms (TGF-beta1 > TGF-beta2 > TGF-beta3). Arachidonic acid, which is one of the most potent inhibitors, is also capable of dissociating TGF-beta-alpha2M* complexes, but higher concentrations are required. Arachidonic acid appears to inhibit TGF-beta-alpha2M* complex formation by binding specifically to alpha2M* as demonstrated by gel filtration chromatography. Arachidonic acid reverses the inhibitory effect of alpha2M* on TGF-beta binding, TGF-beta-induced growth inhibition, and TGF-beta-induced transcriptional activation in mink lung epithelial cells and affects plasma clearance of TGF-beta-alpha2M* complexes in mice. These results show that fatty acids are effective modulators of TGF-beta activity and plasma clearance and may be useful in treating human diseases through their effects on the interaction of TGF-beta and alpha2M*.


Lim, P., K. Sadre-Bazzaz, et al. (2003). "DNA damage and mutations induced by arachidonic acid peroxidation." Biochemistry 42(51): 15036-44.

            Endogenous cellular oxidation of omega6-polyunsaturated fatty acids (PUFAs) has long been recognized as a contributing factor in the development of various cancers. The accrual of DNA damage as a result of reaction with free radical and electrophilic aldehyde products of lipid peroxidation is believed to be involved; however, the genotoxic and mutation-inducing potential of specific membrane PUFAs remains poorly defined. In the present study we have examined the ability of peroxidizing arachidonic acid (AA, 20:4omega6) to induce DNA strand breaks, base modifications, and mutations. The time-dependent induction of single-strand breaks and oxidative base modifications by AA in genomic DNA was quantified using denaturing glyoxal gel electrophoresis. Mutation spectra were determined in XP-G fibroblasts and a repair-proficient line corrected for this defect by c-DNA complementation (XP-G(+)). Mutation frequencies were elevated from approximately 5- to 30-fold over the background following reaction of DNA with AA for various times. The XPG gene product was found to be involved in the suppression of mutations after extended reaction of DNA with AA. Arachidonic acid-induced base substitutions were consistent with the presence of both oxidized and aldehyde base adducts in DNA. The frequency of multiple-base substitutions induced by AA was significantly reduced upon correction for the XPG defect (14% vs 2%, P = 0.0015). Evidence is also presented which suggests that the induced frequency of multiple mutations is lesion dependent. These results are compared to published data for mutations stimulated by alpha,beta-unsaturated aldehydes identified as products of lipid peroxidation.


Lichtenstein, A. H. (2003). "Dietary fat and cardiovascular disease risk: quantity or quality?" J Womens Health (Larchmt) 12(2): 109-14.

            When considering dietary fat quantity, there are two main factors to consider, impact on body weight and plasma lipoprotein profiles. Data supporting a major role of dietary fat quantity in determining body weight are weak and may be confounded by differences in energy density, dietary fiber, and dietary protein. With respect to plasma lipoprotein profiles, relatively consistent evidence indicates that under isoweight conditions, decreasing the total fat content of the diet causes an increase in triglyceride and decrease in high-density lipoprotein (HDL) cholesterol levels. When considering dietary fat quality, current evidence suggests that saturated fatty acids tend to increase low-density lipoprotein (LDL) cholesterol levels, whereas monounsaturated and polyunsaturated fatty acids tend to decrease LDL cholesterol levels. Long-chain omega-3 fatty acids, eicosapentaenoic acid (EPA) (20:5n-3) and docosahexaenoic acid (DHA) (22:6n-3), are associated with decreased triglyceride levels in hypertriglyceridemic patients and decreased risk of developing coronary heart disease (CHD). Dietary trans-fatty acids are associated with increased LDL cholesterol levels. Hence, a diet low in saturated and trans-fatty acids, with adequate amounts of monounsaturated and polyunsaturated fatty acids, especially long-chain omega-3 fatty acids, would be recommended to reduce the risk of developing CHD. Additionally, the current data suggest it is necessary to go beyond dietary fat, regardless of whether the emphasis is on quantity or quality, and consider lifestyle. This would include encouraging abstinence from smoking, habitual physical activity, avoidance of weight gain with age, and responsible limited alcohol intake (one drink for females and two drinks for males per day).


Liabo, J., N. Odden, et al. (2003). "Metabolism of long-chain polyunsaturated fatty acids in rat kidney cells." Ann Nutr Metab 47(1): 22-30.

            The metabolism of long-chain polyunsaturated fatty acids is characterized in tissues, such as liver and heart, especially from studies based on isolated cells incubated with radiolabelled fatty acid substrates. Differently, only little is known about the metabolism of fatty acids in the kidney. It is controversial whether the kidney possesses the ability to desaturate long-chain fatty acids or whether kidney cells are dependent on performed polyunsaturated fatty acids transported from the liver. In this study we used isolated rat kidney cells obtained by a perfusion technique. The cells were incubated with [1-(14)C]-labelled 18:3(n-3) or 20:3(n-6) fatty acids which were incorporated into complex lipids or desaturated/elongated. The lipids were separated by thin-layer chromatography and high-performance liquid chromatography. The present study shows that isolated kidney cells take up and esterify labelled long-chain polyunsaturated fatty acids in a time- and concentration-dependent manner. We have also demonstrated that isolated rat kidney cells only to a minor extent Delta6-desaturate labelled 18:3(n-3) to 18:4 (n-3). Conversely, the Delta 5-desaturation of 20:3(n-6) to 20:4(n-6) is far more active. It may thus be concluded that the kidney, at least in part, must obtain its C(20) and C(22) fatty acids from the circulation, while the active Delta5-desaturase suggests that preformed C(20) fatty acids can be converted to more unsaturated homologues in the kidney.


Li, D. (2003). "Omega-3 fatty acids and non-communicable diseases." Chin Med J (Engl) 116(3): 453-8.

            OBJECTIVE: To review the relation between dietary omega-3 polyunsaturated fatty acids (omega-3 PUFA) and non-communicable diseases. METHOD: Data were collected from scientific journals and conference publications, MEDLINE (1979 - 2002) and current content which included 68 prospective, cross-sectional, case control and dietary-intervention studies. Scientific paper selections were based on the association between omega-3 PUFA and non-communicable diseases. RESULTS: omega-3 PUFA has beneficial effects on increasing heart rate variability, decreasing the risk of stroke, reducing both systolic and diastolic blood pressure, insulin resistance and glucose metabolism. Long chain omega-3 PUFA has anti-cancer and anti-inflammatory activities. omega-3 PUFA has also been reported to have a beneficial effect on attention-deficit/hyperactivity disorder and schizophrenia, and may be effective in managing depression in adults. CONCLUSIONS: Results from epidemiological and dietary intervention studies have shown that omega-3 PUFA represent powerfully a class of bioactive compounds and that dietary intake of omega-3 PUFA plays a critical role in human health in relation to non-communicable diseases.


Levine, L. (2003). "Statins stimulate arachidonic acid release and prostaglandin I2 production in rat liver cells." Lipids Health Dis 2(1): 1.

            Statins inhibit 3-hydroxy-3-methylglutaryl (HMG-CoA) reductase, the rate limiting step in cholesterol synthesis. They are, therefore, used clinically to lower cholesterol and prevent atherosclerosis. Statins have beneficial effects on multiple organ systems. Some of these effects are found in the absence of significant changes in cholesterol levels. Polyunsaturated fatty acids also inhibit HMG-CoA reductase and have many of the same beneficial effects of statins. Four statins (mevastatin, lovastatin, simvastatin and atorvastatin) have been tested in rat liver cells for their effect on arachidonic acid (AA) release and prostaglandin I2 production induced in the presence of lactacystin and 12-O-tetradecanoylphorbol-13-acetate. Each statin stimulated release of AA and induced prostaglandin I2 production. Mevalonate, the product of HMG-CoA reductase, did not reduce the stimulation observed in the presence of simvastatin indicating that HMG-CoA reductase activity is not involved. In view of the multiple biologic properties of AA, the AA released as a result of the action of the statins may play a role in some of the pharmacological effects attributed to these drugs.


Lesa, G. M., M. Palfreyman, et al. (2003). "Long chain polyunsaturated fatty acids are required for efficient neurotransmission in C. elegans." J Cell Sci 116(Pt 24): 4965-75.

            The complex lipid constituents of the eukaryotic plasma membrane are precisely controlled in a cell-type-specific manner, suggesting an important, but as yet, unknown cellular function. Neuronal membranes are enriched in long-chain polyunsaturated fatty acids (LC-PUFAs) and alterations in LC-PUFA metabolism cause debilitating neuronal pathologies. However, the physiological role of LC-PUFAs in neurons is unknown. We have characterized the neuronal phenotype of C. elegans mutants depleted of LC-PUFAs. The C. elegans genome encodes a single Delta6-desaturase gene (fat-3), an essential enzyme for LC-PUFA biosynthesis. Animals lacking fat-3 function do not synthesize LC-PUFAs and show movement and egg-laying abnormalities associated with neuronal impairment. Expression of functional fat-3 in neurons, or application of exogenous LC-PUFAs to adult animals rescues these defects. Pharmacological, ultrastructural and electrophysiological analyses demonstrate that fat-3 mutant animals are depleted of synaptic vesicles and release abnormally low levels of neurotransmitter at cholinergic and serotonergic neuromuscular junctions. These data indicate that LC-PUFAs are essential for efficient neurotransmission in C. elegans and may account for the clinical conditions associated with mis-regulation of LC-PUFAs in humans.


Lemaitre, R. N., I. B. King, et al. (2003). "n-3 Polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study." Am J Clin Nutr 77(2): 319-25.

            BACKGROUND: Little is known about the relation of the dietary intake of n-3 polyunsaturated fatty acids, ie, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from fatty fish and alpha-linolenic acid from vegetable oils, with ischemic heart disease among older adults. OBJECTIVE: We investigated the associations of plasma phospholipid concentrations of DHA, EPA, and alpha-linolenic acid as biomarkers of intake with the risk of incident fatal ischemic heart disease and incident nonfatal myocardial infarction in older adults. DESIGN: We conducted a case-control study nested in the Cardiovascular Health Study, a cohort study of adults aged > or = 65 y. Cases experienced incident fatal myocardial infarction and other ischemic heart disease death (n = 54) and incident nonfatal myocardial infarction (n = 125). Matched controls were randomly selected (n = 179). We measured plasma phospholipid concentrations of n-3 polyunsaturated fatty acids in blood samples drawn approximately 2 y before the event. RESULTS: A higher concentration of combined DHA and EPA was associated with a lower risk of fatal ischemic heart disease, and a higher concentration of alpha-linolenic acid with a tendency to lower risk, after adjustment for risk factors [odds ratio: 0.32 (95% CI: 0.13, 0.78; P = 0.01) and 0.52 (0.24, 1.15; P = 0.1), respectively]. In contrast, n-3 polyunsaturated fatty acids were not associated with nonfatal myocardial infarction. CONCLUSIONS: Higher combined dietary intake of DHA and EPA, and possibly alpha-linolenic acid, may lower the risk of fatal ischemic heart disease in older adults. The association of n-3 polyunsaturated fatty acids with fatal ischemic heart disease, but not with nonfatal myocardial infarction, is consistent with possible antiarrhythmic effects of these fatty acids.


Lee, J. Y., A. Plakidas, et al. (2003). "Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids." J Lipid Res 44(3): 479-86.

            Human subjects consuming fish oil showed a significant suppression of cyclooxygenase-2 (COX-2) expression in blood monocytes when stimulated in vitro with lipopolysaccharide (LPS), an agonist for Toll-like receptor 4 (TLR4). Results with a murine monocytic cell line (RAW 264.7) stably transfected with COX-2 promoter reporter gene also demonstrated that LPS-induced COX-2 expression was preferentially inhibited by docosahexaenoic acid (DHA, C22:6n-3) and eicosapentaenoic acid (EPA, C20:5n-3), the major n-3 polyunsaturated fatty acids (PUFAs) present in fish oil. Additionally, DHA and EPA significantly suppressed COX-2 expression induced by a synthetic lipopeptide, a TLR2 agonist. These results correlated with the preferential suppression of LPS- or lipopeptide-induced NF kappa B activation by DHA and EPA. The target of inhibition by DHA is TLR itself or its associated molecules, but not downstream signaling components. In contrast, COX-2 expression by TLR2 or TRL4 agonist was potentiated by lauric acid, a saturated fatty acid. These results demonstrate that inhibition of COX-2 expression by n-3 PUFAs is mediated through the modulation of TLR-mediated signaling pathways. Thus, the beneficial or detrimental effects of different types of dietary fatty acids on the risk of the development of many chronic inflammatory diseases may be in part mediated through the modulation of TLRs.


Lee, J. Y., J. Ye, et al. (2003). "Reciprocal modulation of Toll-like receptor-4 signaling pathways involving MyD88 and phosphatidylinositol 3-kinase/AKT by saturated and polyunsaturated fatty acids." J Biol Chem 278(39): 37041-51.

            Toll-like receptor-4 (TLR4) can be activated by nonbacterial agonists, including saturated fatty acids. However, downstream signaling pathways activated by nonbacterial agonists are not known. Thus, we determined the downstream signaling pathways derived from saturated fatty acid-induced TLR4 activation. Saturated fatty acid (lauric acid)-induced NFkappaB activation was inhibited by a dominant-negative mutant of TLR4, MyD88, IRAK-1, TRAF6, or IkappaBalpha in macrophages (RAW264.7) and 293T cells transfected with TLR4 and MD2. Lauric acid induced the transient phosphorylation of AKT. LY294002, dominant-negative (DN) phosphatidylinositol 3-kinase (PI3K), or AKT(DN) inhibited NFkappaB activation, p65 transactivation, and cyclooxygenase-2 (COX-2) expression induced by lauric acid or constitutively active (CA) TLR4. AKT(DN) blocked MyD88-induced NFkappaB activation, suggesting that AKT is a MyD88-dependent downstream signaling component of TLR4. AKT(CA) was sufficient to induce NFkappaB activation and COX-2 expression. These results demonstrate that NFkappaB activation and COX-2 expression induced by lauric acid are at least partly mediated through the TLR4/PI3K/AKT signaling pathway. In contrast, docosahexaenoic acid (DHA) inhibited the phosphorylation of AKT induced by lipopolysaccharide or lauric acid. DHA also suppressed NFkappaB activation induced by TLR4(CA), but not MyD88(CA) or AKT(CA), suggesting that the molecular targets of DHA are signaling components upstream of MyD88 and AKT. Together, these results suggest that saturated and polyunsaturated fatty acids reciprocally modulate the activation of TLR4 and its downstream signaling pathways involving MyD88/IRAK/TRAF6 and PI3K/AKT and further suggest the possibility that TLR4-mediated target gene expression and cellular responses are also differentially modulated by saturated and unsaturated fatty acids.


Lebeau, T. and J. M. Robert (2003). "Diatom cultivation and biotechnologically relevant products. Part II: current and putative products." Appl Microbiol Biotechnol 60(6): 624-32.

            While diatoms are widely present in terms of diversity and abundance in nature, few species are currently used for biotechnologically applications. Most studies have focussed on intracellularly synthesised eicosapentaenoic acid (EPA), a polyunsaturated fatty acid (PUFA) used for pharmaceutical applications. Applications for other intracellular molecules, such as total lipids for biodiesel, amino acids for cosmetic, antibiotics and antiproliferative agents, are at the early stage of development. In addition, the active principle component must be identified amongst the many compounds of biotechnological interest. Biomass from diatom culture may be applied to: (1). aquaculture diets, due to the lipid- and amino-acid-rich cell contents of these microorganisms, and (2). the treatment of water contaminated by phosphorus and nitrogen in aquaculture effluent, or heavy metal (bioremediation). The most original application of microalgal biomass, and specifically diatoms, is the use of silicon derived from frustules in nanotechnology. The competitiveness of biotechnologically relevant products from diatoms will depend on their cost of production. Apart from EPA, which is less expensive when obtained from Phaeodactylum tricornutum than from cod liver, comparative economic studies of other diatom-derived products as well as optimisation of culture conditions are needed. Extraction of intracellular metabolites should be also optimised to reduce production costs, as has already been shown for EPA. Using cell immobilisation techniques, benthic diatoms can be cultivated more efficiently allowing new, biotechnologically relevant products to be investigated.


Leaf, A., Y. F. Xiao, et al. (2003). "Prevention of sudden cardiac death by n-3 polyunsaturated fatty acids." Pharmacol Ther 98(3): 355-77.

            This is a review of our present understanding of the mechanism by which the n-3 polyunsaturated fatty acids (PUFA) in fish oils prevent fatal ventricular arrhythmias in animals and cultured heart cells. A brief review of three clinical trials that suggest that these PUFAs prevent sudden cardiac death is also included in order to emphasize the potential importance of these fatty acids in human nutrition. The PUFAs act by stabilizing electrically every cardiac myocyte by modulating conductance of ion channels in the sarcolemma, particularly the fast, voltage-dependent sodium current and the L-type calcium currents, though other ion currents are also affected. Work in progress suggests that the primary site of action of the PUFAs may be on the phospholipid bilayer of the heart cells in the microdomains through which the ion channels penetrate the membrane bilayer in juxtaposition with the ion channels rather than directly on the channel protein itself. These PUFAs then allosterically alter the conformation and conductance of the channels. Both potential benefits and possible adverse effects of the PUFAs in man will be discussed. Knowing that the ion channels have been structurally conserved among all excitable tissues, we tested their effects on the electrophysiology of rat hippocampal CA1 neurons and found that the sodium and calcium ion channels in these neurons were also affected by PUFAs. An attempt to show the place of the PUFAs in human nutrition during the 2-4 million years of our evolution will conclude the review.


Leaf, A., J. X. Kang, et al. (2003). "Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils." Circulation 107(21): 2646-52.


Laurin, D., R. Verreault, et al. (2003). "Omega-3 fatty acids and risk of cognitive impairment and dementia." J Alzheimers Dis 5(4): 315-22.

            It has been suggested that the dietary intake of omega-3 polyunsaturated fatty acids could be inversely related to the risk of dementia and cognitive decline. This analysis examined the association between plasma concentration of omega-3 polyunsaturated fatty acids and prevalence and incidence of cognitive impairment and dementia. Data are reported on subjects 65 years or older who had a complete clinical evaluation at the first two waves (1991-1992 and 1996-1997) of the Canadian Study of Health and Aging. Main outcome measures were cognitive impairment and dementia by mean relative plasma concentrations of fatty acids in the phospholipid fraction at baseline. Results were adjusted for age, sex, education, smoking, alcohol intake, body mass index, history of cardiovascular disease, and apolipoprotein E e4 genotype. In the cross-sectional analysis, no significant difference in omega-3 polyunsaturated fatty acid concentrations was observed between controls and both prevalent cases of cognitive impairment and dementia. In the prospective analysis, a higher eicosapentaenoic acid (p < 0.01) concentration was found in cognitively impaired cases compared to controls while higher docosahexaenoic acid (p < 0.07), omega-3 (p < 0.04) and total polyunsaturated fatty acid (p < 0.03) concentrations were found in dementia cases. These findings do not support the hypothesis that omega-3 polyunsaturated fatty acids play a protective role in cognitive function and dementia.


Lasztity, N., J. Hamvas, et al. (2003). "Effect of enteraly administered N-3 polyunsaturated fatty acids on inflammation, antioxidants and outcome in acute pancreatitis." Clin Nutr 22(S1): S77-8.


Lapillonne, A., S. D. Clarke, et al. (2003). "Plausible mechanisms for effects of long-chain polyunsaturated fatty acids on growth." J Pediatr 143(4 Suppl): S9-16.

            A few studies conducted over the past decade suggest that formulas supplemented with long-chain polyunsaturated n-3 fatty acids may adversely affect growth of preterm infants. Others suggest that a high intake of alpha-linolenic acid (ALA; 18:3 n-3), the precursor of the long-chain polyunsaturated n-3 fatty acids, also may limit growth. The majority of studies, however, have not shown an effect of either long-chain polyunsaturated n-3 fatty acids or their precursor on growth. Nonetheless, the importance of growth during infancy and the possibility that these fatty acids may inhibit growth under some circumstances makes the issue worthy of further consideration. At the very least, plausible mechanisms for such an effect of n-3 PUFA on growth should be considered. These include (1) altered nutrient intake, absorption, and/or utilization; (2) low plasma and tissue contents of arachidonic acid (ARA;20:4 n-6); (3) an imbalance between n-6 and n-3 LCPUFA eicosanoid precursors and, hence, the eicosanoids produced from each; (4) altered membrane characteristics; and (5) effects on gene expression. Each of these is discussed. It is concluded that any or all are feasible but that none can be specifically implicated. Moreover, since few studies were designed specifically to assess growth, the reported effects of n-3 PUFA on growth could represent chance findings secondary to the suboptimal design. Furthermore, although additional data are needed for a definitive conclusion, the observed effects on growth, regardless of mechanism, does not appear to be biologically significant.


Laoteng, K., R. Pongchuachidthai, et al. (2003). "A Mucor rouxii mutant with high accumulation of an unusual trans-linoleic acid (9c,12t-C18:2)." FEMS Microbiol Lett 223(2): 159-65.

            Genetic and biochemical approaches reveal the existence of a gamma-linolenic acid biosynthetic pathway in Mucor rouxii. By treatment with ultraviolet light, combined with low temperature cultivation and filtration enrichment, a mutant defective in polyunsaturated fatty acid synthesis was isolated. Genetic analysis and fatty acid supplementation indicate that the defect occurred in the Delta(12)-desaturation resulting in the absence of cis-linoleic acid and gamma-linolenic acid and in the accumulation of monounsaturated fatty acids. In addition, an unusual fatty acid, trans-linoleic acid (9c,12t-C18:2), which has not been reported previously in this fungus, was found to increase in the mutant. The information gained from the mutant was used to develop the hypothetical pathway of fatty acid desaturation in M. rouxii.


Langer, R., C. Burzler, et al. (2003). "Influence of iodide and iodolactones on thyroid apoptosis. Evidence that apoptosis induced by iodide is mediated by iodolactones in intact porcine thyroid follicles." Exp Clin Endocrinol Diabetes 111(6): 325-9.

            Iodine induced thyroid involution is caused by apoptosis rather than necrosis. This effect of iodide on apoptosis of thyroid epithelial cells may be not a direct one but mediated by iodinated derivatives i.e. of polyunsaturated fatty acids, especially of iodolactones, which have previously shown to inhibit thyroid cell proliferation. We studied the influence on apoptosis of iodide (2 microM and 20 microM) and iodolactone (0.05 microM and 0.5 microM), with and without TSH (1 mU/ml), using a well characterized ex vivo- culture system of intact porcine thyroid follicles in three-dimensional culture. Apoptosis and necrosis was evaluated by electron-microscopy. Stimulation with 2 and 20 microM iodide rapidly induced a rate of apoptosis (4 - 6 %) comparable to about 40-fold lower doses of delta-iodolactone (0.05 microM and 0.5 microM). Addition of TSH (1 mU/ml) caused a slight but not significant further increase of the incidence of apoptotic cells. The rate of necrotic thyroid epithelial cells (1 - 2 %) was similar in all experiments. As delta-iodolactone in very low concentrations--comparable to iodide in higher concentrations--not only inhibits growth but also induces apoptosis, it has to be supposed that the effect of iodide is mediated by this iodinated compound. However, further experiments are necessary to confirm this hypothesis. In addition it could be demonstrated, that apoptosis is a very rapid and limited process in intact follicles. This also may explain, why iodine supplementation even in high doses does not lead to thyroid atrophy but only normalisation of thyroid size. These results confirm that apoptosis is an important regulated and limited mechanism in goiter involution.


Langelier, B., J. P. Furet, et al. (2003). "Docosahexaenoic acid membrane content and mRNA expression of acyl-CoA oxidase and of peroxisome proliferator-activated receptor-delta are modulated in Y79 retinoblastoma cells differently by low and high doses of alpha-linolenic acid." J Neurosci Res 74(1): 134-41.

            The mRNA expression levels of acyl-CoA oxidase (AOX), a key enzyme in very-long-chain fatty acid peroxisomal oxidation, and of peroxisome proliferator-activated receptor-delta (PPAR-delta), a nuclear receptor possibly involved in the gene regulation of brain lipid metabolism, were determined in human Y79 retinoblastoma cells by using real-time quantitative polymerase chain reaction. Cells were dosed with alpha-linolenic acid (18:3n-3), the essential metabolic precursor of the n-3 polyunsaturated fatty acid series that normally gives rise through terminal peroxisomal oxidation to the synthesis of membrane docosahexaenoic acid (22:6n-3, or DHA). The AOX and PPAR-delta relative expression levels increased 2.3 and 3.4 times, respectively, upon dosing of cells with 7 microM 18:3n-3, whereas AOX cDNA abundance decreased by 50% upon dosing with 70 microM 18:3n-3. Concurrently, the DHA content increased by 23% in the membrane ethanolamine-phosphoglycerides from cells dosed with 7 microM 18:3n-3, whereas it decreased by 38% upon dosing with 70 microM 18:3n-3. The DHA's upstream precursors (20:5n-3 and 22:5n-3) both accumulated in cells dosed with 7 or 70 microM 18:3n-3. The 18:3n-3-induced changes in membrane phospholipid fatty acid composition support the hypothesis that the terminal peroxisomal step of n-3 conversion is rate limiting in the Y79 line. The concurrent 7 microM 18:3n-3-induced increase of mRNAs encoding for AOX and for PPAR-delta suggests that 18:3n-3 (or its metabolites) at low concentration could trigger its proper conversion to DHA, possibly through activation of PPAR-delta-mediated transcription of AOX. Decreased membrane DHA content and mRNA expression level of AOX in 70-microM 18:3n-3-dosed cells corroborated the relationship between AOX expression and DHA synthesis and suggested that simultaneous down-regulating events occurred at high concentrations of 18:3n-3.


Lang-Lazdunski, L., N. Blondeau, et al. (2003). "Linolenic acid prevents neuronal cell death and paraplegia after transient spinal cord ischemia in rats." J Vasc Surg 38(3): 564-75.

            PURPOSE: Spinal cord ischemia is a devastating complication of thoracic and thoracoabdominal aortic surgery. Recent studies have suggested a neuroprotective effect of polyunsaturated fatty acids against cerebral ischemia. We investigated the effect of linolenic acid (LIN) in a rat model of spinal cord ischemia. METHODS: Rats were subjected to cross-clamping of the aortic arch and left subclavian artery for 14 minutes. Groups were as follows: sham operation (n = 15); ischemia (n = 15), receiving only vehicle; LIN A (n = 15), receiving LIN before clamping; and LIN B (n = 15), receiving LIN at onset of reperfusion. Neurologic status was assessed daily for 7 days. Spinal cords were harvested for histopathologic analysis, TUNEL staining, and immunohistochemistry for Bax, heat shock protein 70 (HSP70), and nuclear factor-kappaB. RESULTS: Ischemic rats had severe and definitive paraplegia. LIN-treated rats had significantly better neurologic function. Histopathologic analysis disclosed severe neuronal necrosis in the lumbar gray matter of ischemic rats, whereas most of the LIN-treated rats sustained mild to moderate injury. LIN reduced the loss of motor neurons at 7 days (LIN A, 17 +/- 6, and LIN B, 15 +/- 7, versus ischemia, 6 +/- 2 per section; P <.05). LIN prevented apoptotic neuronal cell death, Bax immunoreactivity of the pro-apoptotic protein Bax, and the nuclear transcription factor NF-kappaB. Nuclear HSP70 immunoreactivity was noted exclusively in motor neurons from LIN-treated rats and not in motor neurons from ischemic rats. CONCLUSION: These results suggest that LIN can induce protection against ischemia in the spinal cord, thereby preventing both necrosis and apoptosis of motor neurons.


Lait, C. G., H. T. Alborn, et al. (2003). "Rapid biosynthesis of N-linolenoyl-L-glutamine, an elicitor of plant volatiles, by membrane-associated enzyme(s) in Manduca sexta." Proc Natl Acad Sci U S A 100(12): 7027-32.

            In response to elicitors in the oral secretions of caterpillars, plants produce and release volatile chemicals that attract predators and parasitoids of the caterpillar while it feeds. The most prevalent elicitors are fatty acid amides consisting of 18-carbon polyunsaturated fatty acids coupled with l-glutamine. We demonstrate rapid CoA- and ATP-independent in vitro biosynthesis of the fatty acid amide elicitor, N-linolenoyl-l-glutamine, by microsomal fractions of several alimentary tissues in Manduca sexta. N-linolenoyl-l-glutamine is a structural analog of several other elicitors including volicitin, the first fatty acid amide elicitor identified in caterpillars. The enzyme(s) that catalyzed biosynthesis of N-linolenoyl-l-glutamine was localized within the integral membrane protein fraction extracted from microsomes by Triton X-114 detergent phase partitioning and had maximum activity at alkaline pH. We found no evidence suggesting microbial or tissue-independent biosynthesis of N-linolenoyl-l-glutamine in M. sexta. The in vitro biosynthesis of N-linolenoyl-l-glutamine by membrane-associated enzyme(s) in M. sexta represents direct evidence of fatty acid amide synthesis by caterpillar tissues.


Laiho, K., A. M. Lampi, et al. (2003). "Breast milk fatty acids, eicosanoids, and cytokines in mothers with and without allergic disease." Pediatr Res 53(4): 642-7.

            Allergic disease (AD), including atopic eczema, asthma, allergic rhinitis, and food allergy, is characterized by an imbalance between cytokines produced by distinct T-helper cell subtypes. Whether this imbalance can be transferred from mother to breast milk remains to be established. The objective was to investigate the concentrations and interactions of nutritional and inflammatory factors in breast milk. Breast milk samples were collected from mothers with AD (n = 43) and without AD (n = 51). The concentrations of transforming growth factor (TGF)-beta2, tumor necrosis factor-alpha, IL-4, IL-10, prostaglandin E2, and cysteinyl leukotrienes were measured by immunoassays and fatty acid composition by gas chromatography. Mothers with AD had a lower concentration of TGF-beta2 in breast milk [median (interquartile range), 420 (278-701) ng/L] compared with those without AD [539 (378-1108) ng/L; p = 0.003], whereas other cytokines, prostaglandin E2, and cysteinyl leukotriene concentrations or fatty acid composition were not significantly different between the groups. The breast milk inflammatory factors and fatty acid composition were shown to be related. A positive association was observed between TGF-beta2 and the proportion of polyunsaturated fatty acids (p = 0.038) and a negative association between TGF-beta2 and the proportion of saturated fatty acids (p = 0.029) in breast milk. The reduced TGF-beta2 concentration in the breast milk of mothers with AD may interfere with the development of the mucosal immune system of the breast-fed infant. The observed associations between nutritional and inflammatory factors in breast milk suggest that it may be possible to influence the immunologic properties of breast milk by dietary intervention of the mother.


Lada, A. T. and L. L. Rudel (2003). "Dietary monounsaturated versus polyunsaturated fatty acids: which is really better for protection from coronary heart disease?" Curr Opin Lipidol 14(1): 41-6.

            PURPOSE OF REVIEW: The purpose is to evaluate recent findings concerning dietary fats and the risk of coronary heart disease. Monounsaturated fatty acids are often regarded as healthy, and many have recommended their consumption instead of saturated fatty acids and polyunsaturated fatty acids. Support for the benefits of monounsaturated fatty acids comes largely from epidemiological data, but they have not been an isolated, single variable in such studies. Beneficial effects on the plasma lipid profile and LDL oxidation rates have also been identified. More recent findings have questioned the impact of suspected beneficial effects on coronary heart disease, indicating that studies with more conclusive endpoints are needed. RECENT FINDINGS: Human dietary studies often produce conflicting results regarding the effects of monounsaturated and polyunsaturated fatty acids on the plasma lipid profile. Monounsaturated and polyunsaturated fatty acids both appear to reduce total and LDL-cholesterol compared with saturated fatty acids; however, the effect on HDL is less clear. Lowered HDL levels in response to low-fat or polyunsaturated fatty acid diets and the decreased protection from oxidation of polyunsaturated fatty acid-enriched LDL may not indicate increased coronary heart disease risk. Several lines of evidence also suggest that polyunsaturated fatty acids may protect against atherosclerosis. SUMMARY: Recommendations to substitute monounsaturated fatty acids for polyunsaturated fatty acids or a low-fat carbohydrate diet seem premature without more research into the effects on the development of atherosclerosis. Current opinions favoring monounsaturated fatty acids are based on epidemiological data and risk factor analysis, but are questioned by the demonstrated detrimental effects on atherosclerosis in animal models.


Lada, A. T., L. L. Rudel, et al. (2003). "Effects of LDL enriched with different dietary fatty acids on cholesteryl ester accumulation and turnover in THP-1 macrophages." J Lipid Res 44(4): 770-9.

            LDL enriched with either saturated, monounsaturated, n-6 polyunsaturated, or n-3 polyunsaturated fatty acids were used to study the effects of dietary fatty acids on macrophage cholesteryl ester (CE) accumulation, physical state, hydrolysis, and cholesterol efflux. Incubation of THP-1 macrophages with acetylated LDL (AcLDL) from each of the four diet groups resulted in both CE and triglyceride (TG) accumulation, in addition to alterations of cellular CE, TG, and phospholipid fatty acyl compositions reflective of the individual LDLs. Incubation with monounsaturated LDL resulted in significantly higher total and CE accumulation when compared with the other groups. After TG depletion, intracellular anisotropic lipid droplets were visible in all four groups, with 71% of the cells incubated with monounsaturated AcLDL containing anisotropic lipid droplets, compared with 30% of cells incubated with n-3 AcLDL. These physical state differences translated into higher rates of both CE hydrolysis and cholesterol efflux in the n-3 group. These data suggest that monounsaturated fatty acids may enhance atherosclerosis by increasing both cholesterol delivery to macrophage foam cells and the percentage of anisotropic lipid droplets, while n-3 PUFAs decrease atherosclerosis by creating more fluid cellular CE droplets that accelerate the rate of CE hydrolysis and the efflux of cholesterol from the cell.


Kuno, T., Y. Hirose, et al. (2003). "Promoting effects of high-fat corn oil and high-fat mixed lipid diets on 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis in F344 rats." Oncol Rep 10(3): 699-703.

            Epidemiological studies and laboratory animal model assays suggest that a high intake of dietary fat promotes mammary carcinogenesis as well as colon tumorigenesis. Fat intake in the United States traditionally includes high amounts (30% of total caloric intake) of saturated fatty acids (SFAs) compared to polyunsaturated fatty acids (PUFAs). A recent study suggested that a high-fat mixed-lipid diet (HFML), which simulates the mixed-lipid and high SFAs composition of the average American diet, strongly promotes rat colon carcinogenesis, even when compared to another high-fat diet containing PUFA-rich corn oil. On the other hand, some reports suggest that a high-fat diet rich in n-6 PUFAs promotes mammary carcinogenesis more strongly than a high-fat diet rich in SFAs. Therefore, the present study was designed to compare the effects of HFML, high-fat corn oil diet (HFCO) that is rich in n-6 PUFAs, and a low-fat corn oil diet (LFCO) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female F344 rats. At 7 weeks of age, female F344 rats intended for carcinogen treatment received a gavage of DMBA at a dose level of 65 mg/kg of body weight. Beginning 1 week after carcinogen treatment, groups of rats were then maintained on experimental diets containing LFCO, HFCO or HFML. All rats were evaluated weekly by palpation of mammary tumors and sacrificed 20 weeks after the DMBA treatment. Palpable tumors of mammary glands were detected at the 8, 11, and 19 weeks in the HFCO, HFML and LFCO groups, respectively. Histopathological observation revealed that the incidence and number of mammary tumors in the HFCO group were significantly higher than in the LFCO group. Rats on the HFML diet tended towards a higher incidence and number of mammary tumors compared with the LFCO group, although the correlation was not statistically significant. These results suggest that, for this animal model, both the HFCO and HFML diets promote DMBA-induced mammary carcinogenesis when compared to the LFCO diet, and that the HFCO diet is more tumor-promotional than the HFML diet.


Kumon, Y., R. Yokoyama, et al. (2003). "A new labyrinthulid isolate, which solely produces n-6 docosapentaenoic acid." Appl Microbiol Biotechnol 63(1): 22-8.

            A labyrinthulid strain, L59, was isolated from a leaf floating on seawater collected at the coastal area of Hokkaido Prefecture, Japan. Strain L59 contained only n-6 docosapentaenoic acid ( n-6 DPA) among all the long-chain polyunsaturated fatty acids. The proportion of n-6 DPA in the total fatty acids was 48.1% and the total fatty acids content in the cell dry weight was 26.6%. Many oil bodies were observed in the cell, mostly in the vicinity of cell membranes. The strain had spindle-shaped cell bodies and all cells were surrounded by ectoplasmic net elements. It was also clearly classified in the labyrinthulid group by phylogenetic analysis. In the optimum culture condition, using soybean oil and peptone as carbon and nitrogen sources, 0.53 g of n-6 DPA/l was produced at 20 degrees C in 7 days.


Kuklev, D. V. and W. L. Smith (2003). "A procedure for preparing oxazolines of highly unsaturated fatty acids to determine double bond positions by mass spectrometry." J Lipid Res 44(5): 1060-6.

            A convenient, mild, reliable method has been developed for preparing oxazolines of fatty acids and for using these derivatives to determine double bond locations in long-chain polyunsaturated and polyconjugated fatty acids. Fatty acyl mixed anhydrides are prepared using isobutylchloroformate and then converted to their ethanolamides by treatment with ethanolamine. Ethanolamides are subsequently cyclized to the corresponding oxazolines in >or=85% yields by treatment with trifluoroacetic anhydride under mild conditions (>50 degrees for 30-60 min). This general protocol can also be used to synthesize 4,4-dimethyloxazoline and benzoxazole derivatives of fatty acids. Gas chromatography-mass spectrometry of oxazoline derivatives of fatty acids yields prominent ions diagnostic of the structures of the parent fatty acids and, in the case of unsaturated fatty acids, indicating the positions of the double bonds. The utility of the method is illustrated with several fatty acids, including the conjugated 4E,6E,8E,10E,13Z,16Z,19Z-docosaheptaenoic acid.


Kroes, R., E. J. Schaefer, et al. (2003). "A review of the safety of DHA45-oil." Food Chem Toxicol 41(11): 1433-46.

            Polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA), are natural constituents of the human diet; however, dietary intakes of these fatty acids are below recommended values. The main dietary source of DHA is fatty fish, with lesser amounts provided by shellfish, marine mammals, and organ meats. The addition to traditional food products of refined oils produced by marine microalgae represents potential sources of supplemental dietary DHA. DHA45-oil is manufactured through a multi-step fermentation and refining process using a non-toxigenic and non-pathogenic marine protist. Comprising approximately 45% DHA, and lesser concentrations of palmitic acid and docosapentaenoic acid, DHA45-oil is intended for use in foods as a dietary source of DHA. The safety of DHA45-oil was evaluated in various genotoxicity and acute, subchronic, and reproductive toxicity studies. DHA45-oil produced negative results in genotoxicity assays and demonstrated a low acute oral toxicity in mice and rats. Dietary administration of DHA45-oil to rats in subchronic and one-generation reproductive studies produced results consistent with those observed in oral studies using high concentrations of omega-3 PUFAs from fish or other microalgal-derived oils. The results of these studies, as well as those of various published metabolic, toxicological, and clinical studies with DHA-containing oils, support the safety of DHA45-oil as a potential dietary source of DHA.


Kritchevsky, D., S. A. Tepper, et al. (2003). "Cholesterol vehicle in experimental atherosclerosis 24: avocado oil." J Am Coll Nutr 22(1): 52-5.

            OBJECTIVE: To determine atherogenicity of avocado oil relative to saturated (coconut oil), monounsaturated (olive oil) and polyunsaturated (corn oil) fats. METHODS: New Zealand White rabbits were fed a semipurified diet containing 0.2% cholesterol and 14% fat for 90 days. They were then necropsied and severity of atherosclerosis was determined visually. RESULTS: Coconut oil was the most atherogenic fat. Corn oil was only slightly less atherogenic than either olive or avocado oils. Percentage of serum HDL cholesterol was highest in the rabbits fed the two monounsaturated fats. CONCLUSION: Avocado oil is of the same order of atherogenicity as corn oil and olive oil.


Kratz, M., U. Wahrburg, et al. (2003). "Dietary mono- and polyunsaturated fatty acids similarly increase plasma apolipoprotein A-IV concentrations in healthy men and women." J Nutr 133(6): 1821-5.

            We investigated the effect of dietary fatty acid composition on plasma apolipoprotein (apo) A-IV concentrations. Plasma apo A-IV concentrations were measured by ELISA in plasma of 48 healthy men and women in a controlled dietary study. First, all participants consumed a 2-wk baseline diet rich in saturated fatty acids (SFA). Then, they were randomly assigned to one of three dietary treatments, which contained refined olive oil [rich in monounsaturated fatty acids (MUFA), n = 17], rapeseed oil [rich in MUFA and alpha-linolenic acid [18:3(n-3)], n = 13], or sunflower oil [rich in (n-6) PUFA, n = 18] as the principal source of fat for 4 wk. The plasma concentrations of apo A-IV increased when subjects consumed the diets rich in unsaturated fatty acids, by 16% or 13.0 mg/L [F((2,76)) = 12.874, P < 0.001 by repeated-measures ANOVA]. The increase was not affected by diet group affiliation, gender or apo A-IV genotype. In conclusion, diets rich in unsaturated fatty acids, independent of the degree of unsaturation, gender and apo A-IV genotype, increase plasma apo A-IV concentrations compared with a baseline diet rich in SFA in healthy men and women.


Kozlowska-Wojciechowska, M., M. Jastrzebska, et al. (2003). "Impact of margarine enriched with plant sterols on blood lipids, platelet function, and fibrinogen level in young men." Metabolism 52(11): 1373-8.

            The effects of margarines enriched with omega-6 polyunsaturated fatty acids (PUFA), as well as those containing plant sterols or stanols, on reduction of plasma low-density lipoprotein-cholesterol (LDL-C) have been extensively studied. However, their impact on fibrinogen (Fb) concentration and blood platelet function is much less known. Our research involved 42 healthy male students (average age, 23.7 +/- 1.6) who during the research period were subjected to a controlled regime of nutrition and physical activity. After a period of diet stabilization involving 30 g butter daily in 2 servings, the subjects were randomly divided into 2 groups. In the first group, the butter was replaced by the same quantity of PUFA margarine, while the second group received margarine with added plant sterols instead of butter. The subjects consuming margarine with sterols showed a significant (11%) decrease in LDL-C (P<.001). Margarine rich in PUFA caused a 6% reduction in LDL-C (P<.01), with a simultaneous 3% reduction in high-density lipoprotein-cholesterol (HDL-C) (P<.001). Both types of margarine increased the concentration of Fb (P<.001), without exceeding the normal medium value of 2.8 g/L. After the consumption of margarine with sterols, the adhesion and aggregation time of blood platelets was significantly prolonged after collagen-epinephrine activation. Margarine with sterols, through its antiplatelet activity and the significant reduction of LDL-C, can play a vital role in the nonpharmacologic prevention of circulatory diseases.


Koo, W. W. (2003). "Efficacy and safety of docosahexaenoic acid and arachidonic acid addition to infant formulas: can one buy better vision and intelligence?" J Am Coll Nutr 22(2): 101-7.

            Long chain polyunsaturated fatty acids (LCPUFA) namely arachidonic acid (ARA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3) are highly concentrated in the phospholipid bilayer of biologically active brain and retinal neural membranes and are important in phototransduction and neuronal function. The rationale for adding these LCPUFA to infant formula (IF) was primarily because of their presence in large quantities in the retina and brain and in human milk. In addition, infants fed IF containing LCPUFA and breastfed infants have comparable ARA and DHA levels in red cell and plasma, in contrast to the lower ARA and DHA levels in those fed IF containing only the essential fatty acids: linoleic (LA, 18:2n-6) and linolenic (LNA, 18:3n-3), the precursors to ARA and DHA, respectively. However, functional benefits in particular visual or neural development from IF containing LCPUFA remains controversial. Potential for excessive and/or imbalanced intake of n-6 and n-3 fatty acids exists with increasing fortification of LCPUFA to infant foods other than IF.


Konig, D., S. B. Vaisanen, et al. (2003). "Cardiorespiratory fitness modifies the association between dietary fat intake and plasma fatty acids." Eur J Clin Nutr 57(7): 810-5.

            OBJECTIVES: To investigate the relation between (1) cardiorespiratory fitness and plasma saturated, monounsaturated and polyunsaturated fatty acids and (2) the interactions between cardiorespiratory fitness, dietary fat intake and plasma fatty acid composition. DESIGN: Cross-sectional analysis. SETTING AND SUBJECTS: The subjects were randomly selected, 127 middle-aged Finnish men participating in the DNASCO exercise intervention study. INTERVENTIONS: Cardiorespiratory fitness was determined spiroergometrically, dietary intake of macro- and micronutrients by 4-day food records and plasma fatty acids by gas chromatography. The subjects were divided into tertiles of aerobic fitness. RESULTS: Differences between fitness tertiles were not observed for dietary intake of total fat, and saturated, monounsaturated or polyunsaturated fatty acids (percent of total energy). In contrast, plasma saturated fatty acids were significantly lower (P <0.01) and polyunsaturated fatty acids significantly higher (P <0.05) in the highest fitness tertile compared to the lowest tertile. Dietary saturated fat intake was positively associated with plasma saturated fatty acids (r=0.342; P <0.05) and inversely with plasma polyunsaturated fatty acids (r=-0.453; P <0.01) only in the lowest fitness tertile. In addition, a positive correlation between body mass index and plasma saturated fatty acids (r=0.516; P <0.01) as well as a negative correlation between body mass index and plasma polyunsaturated fatty acids (r=-0.516; P <0.01) was observed in the lowest tertile solely. CONCLUSION: Different levels in cardiorespiratory fitness are associated with different levels in plasma saturated and polyunsaturated fatty acids and lead to modifications in the association between dietary and plasma fatty acids. These findings can perhaps be explained by a reduced hepatic fatty acid and lipoprotein synthesis as well as by an enhanced muscular lipid utilization, which are commonly seen in those who are physically active and who exhibit a higher level of fitness.


Komatsu, W., K. Ishihara, et al. (2003). "Docosahexaenoic acid suppresses nitric oxide production and inducible nitric oxide synthase expression in interferon-gamma plus lipopolysaccharide-stimulated murine macrophages by inhibiting the oxidative stress." Free Radic Biol Med 34(8): 1006-16.

            N-3 polyunsaturated fatty acids (PUFAs) are known to have anti-inflammatory effects. Excess production of nitric oxide (NO) is associated with inflammation. Therefore, we examined the effects of PUFAs on NO production and inducible NO synthase (iNOS) expression by stimulated murine macrophages. One typical n-3 PUFA docosahexaenoic acid (DHA) strongly inhibited NO production and iNOS expression in RAW264 macrophages and mouse peritoneal macrophages in a dose-dependent manner. This inhibition was accompanied by inhibiting the oxidative stress-sensitive transcription factor nuclear factor (NF)-kappaB activation. In stimulated macrophages, intracellular peroxides level was enhanced, but pretreatment of DHA dose-dependently inhibited this enhancement. These results suggest that DHA has an antioxidative effect based on the inhibition of the accumulation of intracellular peroxides, and this inhibition caused the suppression of the activation of NF-kappaB, resulting in the inhibition of NO production and iNOS expression. On the other hand, DHA treatment enhanced the level of intracellular glutathione (GSH), and this enhancement is thought to mediate the activity of DHA because lowering the GSH level by inhibiting GSH biosynthesis reversed the DHA-induced suppression of NO production, NF-kappaB activation, and the accumulation of intracellular peroxides. Our results demonstrate that DHA inhibits NO production in macrophages and this inhibition is, in part, mediated by upregulation of GSH.


Koletzko, B., U. Sauerwald, et al. (2003). "Fatty acid profiles, antioxidant status, and growth of preterm infants fed diets without or with long-chain polyunsaturated fatty acids. A randomized clinical trial." Eur J Nutr 42(5): 243-53.

            Long-chain polyunsaturated fatty acids (LCP) are considered conditionally essential nutrients for the infant born prematurely, and attempts are being made to match fatty acid profiles of formula and breast fed infants. In this double-blind, randomized study we investigated the effects of a formula enriched with both n-6 and n-3 LCP on plasma fatty acid profiles, antioxidant status and growth of premature infants. 29 infants received either a formula devoid of LCP or a LCP supplemented formula (0.5 g/100 g fat linoleic acid metabolites, 0.8 g/100 g fat alpha-linolenic acid metabolites). 17 breast fed infants served as a control group. At study entry as well as two and four weeks later, plasma and urine samples were collected, growth data obtained and food tolerance was documented. At the end of the four week study period, plasma docosahexaenoic acid (DHA) levels of supplemented infants were significantly higher than those of unsupplemented infants and similar to those of infants fed human milk. Plasma n-6 LCP concentrations including arachidonic acid (AA) were similar between groups. The plasma alpha-tocopherol levels of breast fed and supplemented infants were similar and tended to be lower than in infants fed the formula devoid of LCP. Urinary malondialdehyde (MDA) excretion of formula fed infants was significantly higher compared to infants fed human milk, but did not differ between the two formula groups. Parameters of growth and milk tolerance did not differ between groups. Our results demonstrate that plasma LCP levels similar to those of breast fed infants can be achieved with the LCP supplemented formula used in this trial, without evidence of adverse effects of the LCP enrichment.


Kobayashi, M., S. Sasaki, et al. (2003). "Validity of a self-administered food frequency questionnaire used in the 5-year follow-up survey of the JPHC Study Cohort I to assess fatty acid intake: comparison with dietary records and serum phospholipid level." J Epidemiol 13(1 Suppl): S64-81.

            We compared fatty acid intake estimated from our 138-item food frequency questionnaire (FFQ) with 28-day weighed dietary records among a subgroup of JPHC Study Cohort I (102 men and 113 women), and with the corresponding two serum phospholipid levels (88 men). Spearman rank correlation coefficients between fatty acid intakes estimated from FFQ and intakes estimated from DR were as follows: saturated fatty acid, r=0.61 and r=0.60; monounsaturated fatty acid, r=0.50 and r=0.44; for energy adjusted value and Eicosapentaenoic acid (EPA), r=0.62 and r=0.55; docosahexaenoic acid (DHA), r=0.61 and r=0.50; for percentage of total fatty acid intake in men and women, respectively. Spearman rank correlation coefficients between fatty acid intakes estimated from FFQ and the corresponding serum phospholipid levels (% of total fatty acid) were as follows: EPA, r=0.43 and r=0.59; DHA, r=0.35 and r=0.49; for crude value (g/day) and percentage of total fatty acid intake, respectively. In conclusion, relatively high correlations were observed for SFA, MUFA and marine-origin n-3 polyunsaturated fatty acid, whereas we must take into account the indicator of each fatty acid intake when using the data of fatty acid intake assessed with FFQ for JPHC study.


Kobayashi, H., M. Yoshida, et al. (2003). "Comparative study of the product components of lipid oxidation in aqueous and organic systems." Chem Phys Lipids 126(1): 111-20.

            Ethyl esters and phosphatidylcholines (PCs) of polyunsaturated fatty acids (PUFAs) were oxidized in organic solvents, aqueous emulsions, and liposomes in the presence of a radical inducer. Oxidation products and the positional distribution of monohydroperoxide (MHP) were determined by gas chromatography-mass spectrometry (GC-MS) analysis. The total amount of the oxidation products, of PUFA ethyl esters and PCs in organic solvents, increased with an increase in the number of bis-allylic positions. However, the opposite results were obtained in an aqueous emulsion and liposomes. The distribution pattern of MHPs obtained from oxidation of the linolate and alpha-linolenate showed little difference between a chloroform solution and an aqueous emulsion or liposomes. However, there were differences between these systems with the arachidonate, the icosapentaenoate, and docosahexaenoate. These results may be due to the different rate of hydrogen abstraction from bis-allylic positions in the fatty acid moieties, and/or 1,3-cyclization of hydroperoxides in the systems.


Knutsen, S. F., G. E. Fraser, et al. (2003). "Comparison of adipose tissue fatty acids with dietary fatty acids as measured by 24-hour recall and food frequency questionnaire in Black and White Adventists: the Adventist Health Study." Ann Epidemiol 13(2): 119-27.

            PURPOSE: To calibrate and compare intake of different fats and individual fatty acids as assessed with a food frequency questionnaire (FFQ) against that estimated with (i) a series of dietary recalls and; (ii) the relative fat concentration in an adipose tissue biopsy. The FFQ was specially designed for use in a cohort of Seventh-day Adventists. In preparation for a large cohort study investigating the effect of diet on risk of colon, prostate and breast cancer. METHODS: The association of adipose tissue fatty acids and dietary fat intake was assessed in 49 black and 72 white Seventh-day Adventists subjects using 8 different 24-hour recalls, a 200-item food frequency questionnaire (FFQ) and adipose tissue biopsies from each subject. RESULTS: Pearson correlation between fatty acids in adipose tissue and dietary intake as assessed by multiple 24-hour recalls were as follows: Linoleic acid: 0.77 in black and 0.71 in white subjects, respectively; Linolenic acid: 0.68 (blacks) and 0.62 (whites); Total Polyunsaturated fat (PUFA): 0.78 (blacks) and 0.70 (whites); Total Monounsaturated fat (MUFA): 0.35 (blacks) and 0.03 (whites); Total Saturated fat (SFA): 0.46 (blacks) and 0.56 (whites). Correlations between fatty acids in adipose tissue and dietary intake as assessed by FFQ were: Linoleic acid: 0.61 (blacks) and 0.52 (whites), respectively; Linolenic acid: 0.29 (blacks) and 0.49 (whites); PUFA: 0.62 (blacks) and 0.53 (whites); MUFA: 0.07 (blacks) and 0.31 (whites), SFA: 0.21 (blacks) and 0.31 (whites). CONCLUSIONS: Our study confirms findings of others that 24-hour recalls are valid for assessing dietary intake of different types of fat. The FFQ we developed and used in this study gave reasonably valid measures of fatty acid intake in our population and is thus suitable for use in large cohort studies. It had validity comparable to that observed for other FFQs.


Kniazeva, M., M. Sieber, et al. (2003). "Suppression of the ELO-2 FA elongation activity results in alterations of the fatty acid composition and multiple physiological defects, including abnormal ultradian rhythms, in Caenorhabditis elegans." Genetics 163(1): 159-69.

            While the general steps of fatty acid (FA) biosynthesis are well understood, the individual enzymes involved in the elongation of long chain saturated and polyunsaturated FA (PUFA) are largely unknown. Recent research indicates that these enzymes might be of considerable physiological importance for human health. We use Caenorhabditis elegans to study FA elongation activities and associated abnormal phenotypes. In this article we report that the predicted C. elegans F11E6.5/ELO-2 is a functional enzyme with the FA elongation activity. It is responsible for the elongation of palmitic acid and is involved in PUFA biosynthesis. RNAi-mediated suppression of ELO-2 causes an accumulation of palmitate and an associated decrease in the PUFA fraction in triacylglycerides and phospholipid classes. This imbalance in the FA composition results in multiple phenotypic defects such as slow growth, small body size, reproductive defects, and changes in rhythmic behavior. ELO-2 cooperates with the previously reported ELO-1 in 20-carbon PUFA production, and at least one of the enzymes must function to provide normal growth and development in C. elegans. The presented data indicate that suppression of a single enzyme of the FA elongation machinery is enough to affect various organs and systems in worms. This effect resembles syndromic disorders in humans.


Kiyohara, Y., A. Shinohara, et al. (2003). "Dietary factors and development of impaired glucose tolerance and diabetes in a general Japanese population: the hisayama study." J Epidemiol 13(5): 251-8.

            BACKGROUND: There have been few prospective studies on diet and glucose abnormalities as determined by oral glucose tolerance test. METHODS: To investigate the impact of dietary factors on the development of glucose intolerance including diabetes and impaired glucose tolerance, we performed a follow-up survey of 1,075 subjects aged 40-74 years of normal glucose tolerance from 1988 through 1993/1994 by repeated 75 g oral glucose tolerance test and dietary survey. Information on habitual food consumption was obtained using a semiquantitative food frequency method. RESULTS: Of the total subjects studied, 119 (11.1%) developed impaired glucose tolerance and 24 (2.2%) developed diabetes during the follow-up. At baseline, the age-adjusted amount of alcohol intake was significantly higher in males who developed glucose intolerance than in those who did not (26.7 g vs. 15.7 g, p < 0.05), while the polyunsaturated/saturated fatty acids (P/S) ratio was significantly higher in females with future glucose intolerance (1.42 vs. 1.31, p < 0.05). Among the female subjects who developed glucose intolerance, the intake of animal fat less decreased during the follow-up period compared with normal subjects, resulting in a significant decrease in the P/S ratio (-0.09 vs. 0.05, p < 0.05). In a multiple logistic regression analysis, alcohol intake at baseline for males and decreased P/S ratio during the follow-up for females remained a significant risk factor for glucose intolerance independent of other dietary and non-dietary factors as well. CONCLUSIONS: These results suggest that a high intake of alcohol and a decreased P/S ratio contribute to the risk of glucose intolerance in contemporary Japanese.


Kingsley, P. J. and L. J. Marnett (2003). "Analysis of endocannabinoids by Ag+ coordination tandem mass spectrometry." Anal Biochem 314(1): 8-15.

            The neutral arachidonic acid derivatives N-arachidonylethanolamide (anandamide or AEA) and 2-arachidonylglycerol (2-AG) have been identified as endogenous ligands for the cannabinoid receptors. Quantitation of these endocannabinoids from various tissues has been shown to be essential in the elucidation of cannabinoid-mediated processes in vivo. Here, we describe a novel method for the detection and quantitation of AEA and 2-AG from mammalian tissue. We exploit the ability of silver cation to bind to the polyunsaturated arachidonate backbone of both molecules to form the charged species [M+Ag](+). These complexes are amenable to liquid chromatography-electrospray ionization-tandem mass spectrometry analysis, resulting in the simple and specific quantitation of AEA and 2-AG. The limits of detection of 2-AG and AEA are 13 and 14fmol, respectively, on-column. This method provides an alternative to existing methods, which employ derivation and/or selected ion monitoring (when mass spectrometric detection is used), and may facilitate the understanding of the physiological roles of this new class of compounds.


Kim, J. I., T. Tsujino, et al. (2003). "Bezafibrate improves hypertension and insulin sensitivity in humans." Hypertens Res 26(4): 307-13.

            We examined cellular membrane fatty acid composition and insulin sensitivity in patients with mild essential hypertension and hyperlipidemia, and investigated whether bezafibrate, a lipid-lowering drug, could improve elevated blood pressure and insulin sensitivity in these subjects by ameliorating cellular membrane fatty acid composition. Twenty-seven subjects were recruited. Twelve men with mild essential hypertension [systolic blood pressure (SBP) between 140 mmHg and 160 mmHg] and hypertriglyceridemia (plasma triglyceride concentration over 150 mg/dl) were designated the HL group. Fifteen men with mild essential hypertension and normotriglyceridemia (plasma triglyceride concentration below 150 mg/dl) were designated the NL group. Subjects in the HL group were given bezafibrate 400 mg/dl and those in the NL group were given placebo for 3 months. Bezafibrate significantly reduced SBP (140 +/- 2.6 to 131.8 +/- 2.6 mmHg, mean +/- SEM), diastolic blood pressure (DBP) (87.8 +/- 2.0 to 82.8 +/- 2.6 mmHg), fasting plasma triglyceride concentration (225.5 +/- 23.5 to 102.9 +/- 10.9 mg/dl), fasting plasma insulin concentration (9.6 +/- 0.8 to 7.1 +/- 0.8 microU/ml), and homeostasis model assessment scores (HOMA-R, 2.4 +/- 0.2 to 1.7 +/- 0.2), and significantly improved the insulin sensitivity index (56.0 +/- 3.0 to 70.7 +/- 4.8 mg x l2/mmol x mU x min) in the HL group. Regarding erythrocyte membrane fatty acid composition, bezafibrate reduced the percentages of saturated fatty acids (SFA) and increased the percentage of polyunsaturated fatty acids (PUFA). Plasma triglyceride concentrations were positively correlated with HOMA-R (r = 0.50, p < 0.01) and SFA (r = 0.39, p < 0.05), and negatively correlated with PUFA (r = -0.45, p < 0.05) before administration of placebo or bezafibrate. In conclusion, an improvement of hyperlipidemia by bezafibrate may be attributed to reduction of blood pressure and amelioration of insulin sensitivity. Abnormalities in membrane lipid composition may play an important role in these metabolic disorders.


Kim, H., S. Choi, et al. (2003). "Suppression of fatty acid synthase by dietary polyunsaturated fatty acids is mediated by fat itself, not by peroxidative mechanism." J Biochem Mol Biol 36(3): 258-64.

            This study examined the effect of dietary polyunsaturated fatty acids (PUFA) that were supplemented with vitamin E on lipid peroxidation, glutathione-dependent detoxifying enzyme system activity, and lipogenic fatty acid synthase (FAS) expression in rat liver. Male Sprague-Dawley rats were fed semipurified diets containing either 1% (w/w) corn oil or 10% each of beef tallow, corn oil, perilla oil, and fish oil for 4 wk. Alpha-tocopherol was supplemented in perilla oil (0.015%) and fish oil (0.019%). Hepatic thiobarbituric acid reactive substances, an estimate of lipid peroxidation, were not significantly different among the dietary groups. The glutathione peroxidase, glutathione reductase, and glutathione S-transferase activities were all elevated by the polyunsaturated fats, especially fish oil. The activity of FAS was reduced in the polyunsaturated fat-fed groups in the order of fish oil, perilla oil, and corn oil. The mRNA contents decreased in rats that were fed the 10% fat diets, particularly polyunsaturated fats, compared with the rats that were fed the 1% corn oil diet. Similarly, the inhibitory effect was the greatest in fish oil. These results suggest that lipid peroxidation can be minimized by vitamin E; PUFA in itself has a suppressive effect on lipogenic enzyme.


Kim, K. M., B. H. Jung, et al. (2003). "Alteration of urinary profiles of endogenous steroids and polyunsaturated fatty acids in thyroid cancer." Cancer Lett 202(2): 173-9.

            To explore the possible involvement of a relationship between steroids and polyunsaturated fatty acids (PUFAs) in thyroid cancer, we studied the concentration levels of 21 endogenous urinary androgens and glucocorticoids, and 6 urinary PUFAs in female patients with thyroid cancer (n=29, 49.4+/-12.6 years) and in normal female subjects (n=20, 48.3+/-11.9 years). Using gas chromatography-mass spectrometry in selected ion-monitoring mode, we performed quantification of androgens, glucocorticoids, and PUFAs. In the case of the urinary androgens and the glucocorticoids, the concentration of androgens was not altered between patients with thyroid cancer and normal controls. However, the concentration of glucocorticoid significantly decreased in patients with thyroid cancer compared to that of the normal controls. Also, in case of urinary PUFAs, the precursor of cholesterol, the concentration of linoleic acid, arachidonic acid, and docosahexaenoic acid (DHA) were decreased in patient with thyroid cancer (P<0.05). In this results, it can be concluded that the glucocorticoids milieu induced from the decreasing urinary concentration of DHA may exert an important influence upon thyroid cancer. Consequently, the change of urinary glucocorticoids concentration may play an important role in thyroid cancer.


Kikugawa, K., Y. Yasuhara, et al. (2003). "Effect of supplementation of n-3 polyunsaturated fatty acids on oxidative stress-induced DNA damage of rat hepatocytes." Biol Pharm Bull 26(9): 1239-44.

            The effect of supplementation of n-3 polyunsaturated fatty acids (PUFA) on oxidative stress-induced DNA damage of rat hepatocytes was examined. Male Wistar rats were fed a diet containing safflower oil (control n-6 PUFA diet) or fish oil (n-3 PUFA diet) in 50 g/kg of dried diet and an equal amount of vitamin E in 59 mg/kg of dried diet for 6 weeks. The liver of rats fed safflower oil was rich in n-6 PUFA, whereas that of rats fed fish oil was rich in n-3 PUFA. Isolated hepatocytes were treated in vitro with ADP/Fe (II) ion or hydrogen peroxide at 37 degrees C for 30 min to induce oxidative stress. The degree of lipid peroxidation was assessed by the levels of phospholipid hydroperoxides and thiobarbituric acid-reactive substances. The degree of oxidative DNA damage was assessed based on comet-type characterization in alkaline single-cell gel electrophoresis and 8-hydroxy-deoxyguanosine levels. In both ADP/Fe(II) ion and hydrogen peroxide oxidation, the degree of lipid peroxidation of hepatocytes increased in both diet groups, and the level of increase in the fish oil diet group was slightly higher than that in the safflower oil diet group. In ADP/Fe(II) ion oxidation, the degree of DNA damage increased in both diet groups, but there were no significant differences in the level of increase. In contrast, in hydrogen peroxide oxidation, the degree of DNA damage increased in both diet, and the increase in the fish oil diet group was significantly lower than that in the safflower oil diet group. It is unlikely that an n-3 PUFA-rich diet enhances oxidative stress-induced hepatocyte DNA damage as compared with the control n-6 PUFA-rich diet.


Kikugawa, K., Y. Yasuhara, et al. (2003). "Protective effect of supplementation of fish oil with high n-3 polyunsaturated fatty acids against oxidative stress-induced DNA damage of rat liver in vivo." J Agric Food Chem 51(20): 6073-9.

            The present study was undertaken to know the effect of supplementation of fish oil with high n-3 polyunsaturated fatty acids (PUFA) on oxidative stress-induced DNA damage of rat liver in vivo. Male Wistar rats were fed a diet containing fish oil or safflower oil with high n-6 PUFA at 50 g/kg of diet and an equal amount of vitamin E at 59 mg/kg of diet for 6 weeks. Livers of rats fed fish oil were rich in n-3 PUFA, whereas those of rats fed safflower oil were rich in n-6 PUFA. Ferric nitrilotriacetate was intraperitoneally injected to induce oxidative stress. The degree of lipid peroxidation of the liver was assessed by the levels of phospholipid hydroperoxides and thiobarbituric acid-reactive substances (TBARS), and the degree of oxidative DNA damage was assessed by comet type characterization in alkaline single-cell gel electrophoresis and 8-hydroxy-2'-deoxyguanosine levels. The levels of TBARS of the livers of the fish oil diet group increased to a greater extent than those of the safflower oil diet group, whereas the levels of the hydroperoxides of the livers of both diet groups increased to a similar extent. The vitamin E level of livers of the fish oil diet group was remarkably decreased. The degree of DNA damage of both diet groups was increased, but the increased level of the fish oil diet group was remarkably lower than that of the safflower oil diet group. The above results indicate that fish oil supplementation does not enhance but appears to protect against oxidative stress-induced DNA damage and suggest that lipid peroxidation does not enhance but lowers the DNA damage.


Kew, S., T. Banerjee, et al. (2003). "Relation between the fatty acid composition of peripheral blood mononuclear cells and measures of immune cell function in healthy, free-living subjects aged 25-72 y." Am J Clin Nutr 77(5): 1278-86.

            BACKGROUND: There is little information about the relation between the fatty acid composition of human immune cells and the function of those cells over the habitual range of fatty acid intakes. OBJECTIVE: The objective of the study was to determine the relation between the fatty acid composition of human peripheral blood mononuclear cell (PBMC) phospholipids and the functions of human immune cells. DESIGN: One hundred fifty healthy adult subjects provided a fasting blood sample. The phagocytic and oxidative burst activities of monocytes and neutrophils were measured in whole blood. PBMCs were isolated and used to measure lymphocyte proliferation in response to the T cell mitogen concanavalin A and the production of cytokines in response to concanavalin A or bacterial lipopolysaccharide. The fatty acid composition of plasma and PBMC phospholipids was determined. RESULTS: Wide variations in fatty acid composition of PBMC phospholipids and immune cell functions were identified among the subjects. The proportions of total polyunsaturated fatty acids (PUFAs), of total n-6 and n-3 PUFAs, and of several individual PUFAs in PBMC phospholipids were positively correlated with phagocytosis by neutrophils and monocytes, neutrophil oxidative burst, lymphocyte proliferation, and interferon gamma production. The ratios of saturated fatty acids to PUFAs and of n-6 to n-3 PUFAs were negatively correlated with these same immune functions. The relation of PBMC fatty acid composition to monocyte oxidative burst was the reverse of its relation to monocyte phagocytosis and neutrophil oxidative burst. CONCLUSION: Variations in the fatty acid composition of PBMC phospholipids account for some of the variability in immune cell functions among healthy adults.


Kew, S., T. Banerjee, et al. (2003). "Lack of effect of foods enriched with plant- or marine-derived n-3 fatty acids on human immune function." Am J Clin Nutr 77(5): 1287-95.

            BACKGROUND: Greatly increasing dietary flaxseed oil [rich in the n-3 polyunsaturated fatty acid (PUFA) alpha-linolenic acid (ALA)] or fish oil [rich in the long-chain n-3 PUFAs eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids] can reduce markers of immune cell function. The effects of more modest doses are unclear, and it is not known whether ALA has the same effects as its long-chain derivatives. OBJECTIVE: The objective was to determine the effects of enriching the diet with ALA or EPA+DHA on immune outcomes representing key functions of human neutrophils, monocytes, and lymphocytes. DESIGN: In a placebo-controlled, double-blind, parallel study, 150 healthy men and women aged 25-72 y were randomly assigned to 1 of 5 interventions: placebo (no additional n-3 PUFAs), 4.5 or 9.5 g ALA/d, and 0.77 or 1.7 g EPA+DHA/d for 6 mo. The n-3 PUFAs were provided in 25 g fat spread plus 3 oil capsules. Blood samples were taken at 0, 3, and 6 mo. RESULTS: The fatty acid composition of peripheral blood mononuclear cell phospholipids was significantly different in the groups with higher intakes of ALA or EPA+DHA. The interventions did not alter the percentages of neutrophils or monocytes engaged in phagocytosis of Escherichia coli or in phagocytic activity, the percentages of neutrophils or monocytes undergoing oxidative burst in response to E. coli or phorbol ester, the proliferation of lymphocytes in response to a T cell mitogen, the production of numerous cytokines by monocytes and lymphocytes, or the in vivo delayed-type hypersensitivity response. CONCLUSION: An intake of <or= 9.5 g ALA/d or <or= 1.7 g EPA+DHA/d does not alter the functional activity of neutrophils, monocytes, or lymphocytes, but it changes the fatty acid composition of mononuclear cells.


Kew, S., E. S. Gibbons, et al. (2003). "The effect of feeding structured triacylglycerols enriched in eicosapentaenoic or docosahexaenoic acids on murine splenocyte fatty acid composition and leucocyte phagocytosis." Br J Nutr 90(6): 1071-80.

            The effects of altering the type of n-3 polyunsaturated fatty acid (PUFA) in the mouse diet on the ability of monocytes and neutrophils to perform phagocytosis were investigated. Male weanling mice were fed for 7 d on one of nine diets which contained 178 g lipid/kg and which differed in the type of n-3 PUFA and in the position of these in dietary triacylglycerol (TAG). The control diet contained 4.4 g alpha-linolenic acid/100 g total fatty acids. In the other diets, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) replaced a proportion (50 or 100 %) of the alpha-linolenic acid, and were in the sn-2 or the sn-1(3) position of dietary TAG. There were significant increases in the content of n-3 PUFA in spleen-cell phospholipids when EPA or DHA was fed. These increases were largely independent of the position of EPA or DHA in dietary TAG except when EPA was fed at the highest level, when the incorporation was greater when it was fed in the sn-2 than in the sn-1(3) position. There was no significant effect of dietary DHA on monocyte or neutrophil phagocytic activity. Dietary EPA dose-dependently decreased the number of monocytes and neutrophils performing phagocytosis. However, when EPA was fed in the sn-2 position, the ability of active monocytes or neutrophils to engulf bacteria was increased in a dose-dependent fashion. This did not occur when EPA was fed in the sn-1(3) position. Thus, there appears to be an influence of the position of EPA, but not of DHA, in dietary TAG on its incorporation into cell phospholipids and on the activity of phagocytic cells.


Kelly, O., S. Cusack, et al. (2003). "The effect of polyunsaturated fatty acids, including conjugated linoleic acid, on calcium absorption and bone metabolism and composition in young growing rats." Br J Nutr 90(4): 743-50.

            The effect of polyunsaturated fatty acids (PUFA), in particular conjugated linoleic acid (CLA), on Ca and bone metabolism is unclear. In a 2x2 factorial design study, forty male 4-week-old rats were fed a control diet containing 70 g added fat (soyabean oil (SBO; n-6 PUFA-rich diet) or menhaden oil-safflower oil (MSO; n-3 PUFA-rich diet))/kg diet with 0 or 10 g CLA/kg for 8 weeks. Ex vivo prostaglandin E2 biosynthesis by bone organ culture was significantly higher (P<0.001) in rats consuming SBO compared with MSO, irrespective of CLA. Addition of the CLA treatment to either diet further lowered (P<0.05) ex vivo prostaglandin E2 production. Neither PUFA type nor CLA altered circulating or femoral mRNA levels of osteocalcin (a marker of bone formation) or insulin-like growth factor-I (a mediator of bone metabolism). While urinary pyridinium crosslinks levels (markers of bone resorption) were unaffected by CLA irrespective of PUFA type, they were significantly higher (P<0.05) in rats consuming SBO compared with MSO irrespective of CLA. Net fractional (%) and absolute (mg) Ca absorption were significantly (P<0.01 and P<0.05 respectively) higher in CLA-supplemented than unsupplemented animals fed on the n-3 PUFA-rich diet, whereas CLA had no effect in animals fed the n-6 PUFA-rich diet. There was no effect of CLA supplementation on bone mineral mass. In conclusion, CLA supplementation over 8 weeks appeared to enhance Ca absorption in young growing rats fed an n-3 PUFA-rich diet, but had no measurable effect on bone metabolism or bone mass over this time frame.


Kawai, Y., Y. Kato, et al. (2003). "Immunochemical detection of a novel lysine adduct using an antibody to linoleic acid hydroperoxide-modified protein." J Lipid Res 44(6): 1124-31.

            We have previously prepared the polyclonal antibody to the 13-hydroperoxyoctadecadienoic acid-modified protein (13Ab) (Kato et al. 1997. J. Lipid Res. 38: 1334-1346), however, the epitopes have not yet been structurally identified. In this study, we identified a novel amide-type adduct as one of the major epitopes of 13Ab and characterized the endogenous formation. Upon incubation of the lysine derivative with peroxidized linoleic acid, the formation of N epsilon -(azelayl)lysine (AZL) was confirmed using liquid chromatography-mass spectrometry. The chemically synthesized azelayl protein was significantly recognized by 13Ab. The peroxidation products of different polyunsaturated fatty acids also generated several analogous carboxyalkylamide-type adducts to AZL by the reaction with the lysine derivative, whereas 13Ab specifically recognized AZL, suggesting that the AZL moiety may be one of the major epitopes of 13Ab. The immunoreactive materials of 13Ab were immunohistochemically detected in atherosclerotic lesions from hypercholesterolemic rabbits. More strikingly, the immunoreactivity was significantly enhanced when the sections were treated with alkali or phospholipase A2 for hydrolyzing the ester bonds prior to the staining. These results suggest that the lipid hydroperoxide-derived carboxylic adducts, such as AZL, and their esters linked with phospholipids may be generated in vivo and involved in the pathogenesis of atherosclerosis associated with oxidative stress.


Katan, M. B., J. L. Harryvan, et al. (2003). "n-3 fatty acids in human fat tissue aspirates are stable for up to 6 y." Eur J Clin Nutr 57(7): 816-8.

            OBJECTIVES: The content of n-3 (omega-3) polyunsaturated fatty acids in fat tissue is a valid indicator of their long-term consumption. We studied the stability of n-3 fatty acids in human subcutaneous fat microbiopsies after 6 and 11 y of storage. DESIGN: Microbiopsies were taken from a lump of human adipose tissue and stored at +20 and -80 degrees C. SETTING: Laboratory study. RESULTS: After 5.6 y at -80 degrees C the proportion of six out of seven highly polyunsaturated fatty acids varied between 91 and 102% (mean 97%) of their baseline values. Storage at +20 degrees C yielded recoveries between 82 and 105%. After 11 y at -80 degrees C the proportions in the original lump of tissue ranged from 88 to 101% (mean 94%). CONCLUSION: n-3 fatty acids in stored fat tissue aspirates are stable for 6-11 y, and are suitable markers of baseline diet in long-term epidemiological studies. SPONSORSHIP: Wageningen Centre for Food Sciences.


Kark, J. D., N. A. Kaufmann, et al. (2003). "Adipose tissue n-6 fatty acids and acute myocardial infarction in a population consuming a diet high in polyunsaturated fatty acids." Am J Clin Nutr 77(4): 796-802.

            BACKGROUND: The Jewish population of Israel consumes a diet rich in n-6 polyunsaturated fatty acids (PUFAs), principally linoleic acid. The consequences of this diet for ischemic heart disease (IHD) remain unclear. OBJECTIVE: We assessed the association of adipose tissue n-6 fatty acids, which are derived entirely from the diet, with acute myocardial infarction (AMI). DESIGN: A total of 180 cases and 492 IHD-free controls aged 25-64 were included in a population-based case-control study of Jerusalem residents hospitalized with a first AMI. Diet was assessed by the use of a food-frequency questionnaire and adipose tissue fatty acids by gas chromatography of biopsy samples taken from subcutaneous gluteal tissue. The data were analyzed by multivariate logistic regression. RESULTS: Dietary PUFAs (: 10.1% of energy) correlated (r = 0.43, P < 0.001) with adipose tissue linoleic acid, which constituted 25.6% of storage fatty acids. High intakes of linoleic acid were not associated with excess risk of AMI (age- and sex-adjusted odds ratio for the third versus the first tertile: 0.96; 95% CI: 0.62, 1.48; NS). In contrast, arachidonic acid, the long chain n-6 derivative of linoleic acid, was positively associated with AMI (age- and sex-adjusted odds ratio: 2.12; 95% CI: 1.33, 3.36; P = 0.004). With multivariate adjustment, there was no evidence for an adverse association of linoleic acid with AMI, whereas the risk associated with arachidonic acid persisted, albeit attenuated. CONCLUSIONS: A very high linoleic acid intake does not appear to confer increased risk of nonfatal AMI. Nonetheless, the increased risk associated with arachidonic acid, a finding that requires confirmation, tempers an inference that diets rich in n-6 fatty acids are safe vis-a-vis coronary health.


Karaman, A., S. Demirbilek, et al. (2003). "Protective effect of polyunsaturated phosphatidylcholine on liver damage induced by biliary obstruction in rats." J Pediatr Surg 38(9): 1341-7.

            BACKGROUND/PURPOSE: Persistent inflammatory response secondary to congenital or acquired biliary choleastasis plays an important role in the pathophysiology of hepatic tissue damage. The polyunsaturated fatty acids (PUFA) have been shown to suppress the inflammatory reactions in vivo and in vitro. PUFA has been shown also to protect against various types of experimental liver damage in animal models and isolated hepatocytes. Therefore, the aim of this study was to investigate the protective effect of PUFA administration on liver damage using the rat chronic biliary obstruction model. METHODS: Swiss albino rats of either sex were divided into 4 groups as follows: control group (group 1, 10 rats); rats with sham operation and treated with saline group 2, 10 rats); rats with biliary obstruction (group 3, 15 rats); and polyunsaturated phophatidylcholine (PPC)-treated rats with biliary obstruction (Group 4, 15 rats). Biliary obstruction was induced by double ligation and division of the common bile duct. PUFA treatment was started 2 weeks later from biliary obstruction in doses of 50 mg/d per rat and continued for 2 weeks. All animals were killed after 4 weeks of common bile duct ligation or sham operation. Liver damage and cholestasis were determined by biochemical and histologic examinations. RESULTS: The data showed a decrease in plasma bilirubin level (both conjugated and unconjugated) and liver enzyme levels (AST, ALT, AP, GGT, 5'-NT) in group 4, when compared with group 3 (P <.05). Tissue levels of malondialdehyde (MDA) in group 4 was 20.00 +/- 2.93 compared with that in group 3, 27.12 +/- 2.96 (P <.05). Administration of PUFA to the biliary obstructed rats resulted in inhibition of collagen accumulation (P <.05) and ductal proliferation (P <.05). CONCLUSIONS: PUFA reduced liver damage, ductular proliferation, and fibrosis in biliary obstructed rats. These effects suggest that it might be a useful agent to preserve liver function in patients with biliary obstruction such as biliary atresia.


Kansci, G., D. C. Mossebo, et al. (2003). "Nutrient content of some mushroom species of the genus Termitomyces consumed in Cameroon." Nahrung 47(3): 213-6.

            The nutrient content (water, lipids, proteins, ashes, crude fibres) of six mushroom species (Termitomyces le Testui, T. aurantiacus, T. schimperi, T. mammformis, T. mboudaeina Mossebo sp. nov., and T. subcypeatus forme bisporus sp. nov.) of the genus Termitomyces from Cameroon was determined.These mushrooms have a high water content (83.3-94.3 g/100 g wet matter) and contain more lipids than species from temperate countries (2.5-5.4 g/100 g dry weight), with high proportions of polyunsaturated fatty acids (45.1-65.1% of total fatty acid methyl esters) and remarkable proportions of crude fibres (17.5-24.7 g/ 100 g dry weight). Their protein content varied between 15.1 and19.1 g/100 g dry weight and ash content between 5.2 and 14.4. The species T. mammiformis was found particularly rich in minerals with 14.4 g ash/ 100 g dry material, that is up to 2.4 g/100 g fresh weight.


Kang, W. and H. Saito (2003). "Oral omega-3 polyunsaturated fatty acids (N3PUFA) and arginine supplementation modulate peritoneal resident cell nuclear factor kappa B (NFkappaB) activity." Clin Nutr 22(S1): S40-1.


Kakela, R., P. Somerharju, et al. (2003). "Analysis of phospholipid molecular species in brains from patients with infantile and juvenile neuronal-ceroid lipofuscinosis using liquid chromatography-electrospray ionization mass spectrometry." J Neurochem 84(5): 1051-65.

            Phospholipids (PL) in cerebral cortex from patients with infantile (INCL or CLN1) and juvenile (JNCL or CLN3) forms of neuronal ceroid-lipofuscinosis (NCL) and controls were analysed by normal phase HPLC and on-line electrospray ionization ion-trap mass spectrometric detection (LC-ESI-MS). The method provided quantitative data on numerous molecular species of different PL classes, which are not achieved by using the conventional chromatographic methods. Compared with the controls, the INCL brains contained proportionally more phosphatidylcholine (PC), and less phosphatidylethanolamine (PE) and phosphatidylserine (PS). Different molecular species of PC, PE, PS, phosphatidylinositol and sphingomyelin were quantified using multiple internal PL standards that differed in fatty acyl chain length and thus allowed correction for chain length dependency of instrument response. In INCL cortex, which had lost 65% of the normal PL content, the proportions of polyunsaturated molecular species, especially the PS and PE that contained docosahexaenoic acid (22:6n-3), were dramatically decreased. The membranes may have adapted to this alteration by increasing the proportions of PL molecules substituted with monounsaturated and short-chain fatty acids. Lysobisphosphatidic acid was highly elevated in the INCL brain and consisted mostly of polyunsaturated species. It is possible that changes in the composition of PL membranes accelerate progression of INCL by altering signalling and membrane trafficking in neurons.


Kaempf-Rotzoll, D. E., G. Hellstern, et al. (2003). "Influence of long-chain polyunsaturated fatty acid formula feeds on vitamin E status in preterm infants." Int J Vitam Nutr Res 73(5): 377-87.

            It has been recommended to supplement formulas for preterm infants with n-3 and n-6 long-chain polyunsaturated fatty acids (LCP) to improve growth, visual acuity, and neurodevelopmental performance. However, large amounts of LCP may increase lipid peroxidation and oxidative stress in preterm infants. We investigated if, under high supplementation of natural tocopherols, LCP addition to formula can be performed safely without causing tocopherol depletion in cell membranes. Thirty-one healthy preterm infants with gestational ages from 28 to 32 weeks were evaluated in a prospective, randomized study from birth to day 42. Nine infants received an n-3 and n-6 LCP-enriched formula (A), eleven infants a standard formula (B), and eleven infants breast milk (control group). Alpha- and gamma-tocopherol extracts were added to both formulas, amounting to five times the value in breast milk (2.3 mg/dL in both formulas versus 0.45 mg/dL in breast milk). Erythrocyte arachidonic acid (AA) and docosahexaenoic acid (DHA) in the phosphatidylethanolamine fraction were similar in the three groups over the study period, whereas a significant reduction of erythrocyte AA and DHA could be detected in the phosphatidylcholine fraction in all three groups from day 14 onwards, when compared to respective cord blood values, with lowest values in the standard formula group. Amazingly, levels of alpha- and gamma-tocopherol were higher in plasma, erythrocytes, platelets, monocytes, and polymorphonuclear leukocytes with LCP supplementation as compared to standard formula and breast milk from day 7 onwards, whereas in buccal mucosal cells, this was not the case until day 42. Gammatocopherol uptake in the LCP-supplemented group was also significantly higher in all cell fractions studied from day 7 onwards. We therefore hypothesize that the LCP supplementation used in formula A improves tocopherol solubility and stability in biological membranes. Under high-dose vitamin E addition to n-3 and n-6 LCP-supplemented formula, no evidence for tocopherol depletion and furthermore, high accumulation of tocopherols, can be detected in healthy preterm infants.


Julius, U. (2003). "Fat modification in the diabetes diet." Exp Clin Endocrinol Diabetes 111(2): 60-5.

            The modification of dietary fat in the diet of diabetic patients is of interest with respect to metabolic and other consequences of this modification. To begin with the data are reviewed for the use of monounsaturated fatty acids (MUFA) in the diabetes diet. Compared to a carbohydrate-rich diet, glucose concentrations are lower. Blood pressure was also found to be lower. There were no major differences with respect to lipid concentrations. HDL-cholesterol levels tended to be higher after a MUFA-rich diet. In type-1 diabetic patients, the number of circulating big VLDL particles was greater after a MUFA diet than after a carbohydrate-rich diet. Comparisons were also made between diets enriched with MUFA and with polyunsaturated fatty acids (PUFA). With respect to lipid concentrations, different groups observed different effects. While one group saw no differences in fasting lipids, they measured a higher remnant-like particle cholesterol after a diet enriched with MUFA. Another group found higher total and LDL-cholesterol levels after a PUFA-rich diet than after a MUFA-diet. In their study, fasting glucose, insulin and fasting chylomicrons and postprandial chylomicrons and VLDL were higher following the PUFA diet. A MUFA-rich diet increased endothelium-dependent flow-mediated dilatation in the superficial femoral artery. Alpha-linolenic acid appears to be a precursor of eicospentaenoic and docosahexaenoic fatty acids. As a diet rich in n-6 PUFA reduces this conversion, a n-6/n-3 PUFA ratio not exceeding 4 - 6 should be observed. No prospective data are available for alpha-linolenic acid in diabetic patients. The review summarizes the results of the Lyon Diet Heart Study and the Nurses' Health Study. Both studies saw a reduced cardiovascular risk associated with a higher intake of alpha-linolenic acid. Finally, data on the effects of fish oil are given. The latter has a clearly expressed triglyceride-lowering effect. Data with respect to glucose control are heterogeneous. Major studies did not find any influence in glucose concentrations. Hepatic glucose production and peripheral insulin sensitivity remained constant. Evidently, nerve function can be improved by fish oil. Data have been compiled comparing the effects of fish oil with those of olive oil, linseed oil and sunflower oil.


Joy, C. B., R. Mumby-Croft, et al. (2003). "Polyunsaturated fatty acid supplementation for schizophrenia." Cochrane Database Syst Rev(2): CD001257.

            BACKGROUND: Limited evidence supports a hypothesis suggesting that schizophrenic symptoms may be the result of altered neuronal membrane structure and metabolism. This structure and metabolism is dependent on blood plasma levels of certain essential fatty acids and their metabolites. OBJECTIVES: To review the effects polyunsaturated fatty acids for people with schizophrenia. SEARCH STRATEGY: The initial search of 1998 was updated. We searched the Cochrane Schizophrenia Group's Register (July 2002), and authors of included studies and relevant pharmaceutical companies were contacted. SELECTION CRITERIA: All randomised clinical trials of polyunsaturated fatty acid treatment for schizophrenia. DATA COLLECTION AND ANALYSIS: Reviewers, working independently, selected, quality assessed, and extracted relevant data. Analysis was on an intention-to-treat basis. Where possible and appropriate Relative Risk (RR) and their 95% confidence intervals (CI) were calculated and the number needed to treat (NNT) estimated. For continuous data, weighted mean differences (WMD) and their 95% confidence intervals were calculated. Data were inspected for heterogeneity. MAIN RESULTS: Five short small studies (n=313) were included. One small study (n=30) suggested that an omega-3 EFA (ecisapentenoic acid (EPA) enriched oil) may have some antipsychotic properties when compared with placebo, even if not given as a supplement to standard drugs (RR not needing antipsychotic drugs 0.73 CI 0.54 to 1.00; RR less than 25% improvement in PANSS 0.54 CI 0.3 to 0.96, NNT 3 CI 2 to 29). Other studies comparing omega-3 EFA's with placebo as a supplement to antipsychotics were too small to be conclusive. There was a suggestion that people already on antipsychotics when given omega-3 EFA supplementation had greater improvement of mental state compared to those receiving a placebo supplementation but the result were not significant (n=29, 1 RCT, RR <25% improvement in PANSS 0.62 CI 0.37 to 1.05). However, the mental state of both medicated and un-medicated patients was significantly better for those receiving omega-3 EFA supplementation (n=59, 2 RCTs, RR <25% improved on PANSS 0.58 CI 0.39 to 0.85, NNT 3 CI 2-8). Medium term data, however, did not favour either group (n=87, 1 RCT, MD PANSS endpoint -1.0 CI -8.15 to 6.15). All studies had low attrition (<10% total, n=271, 4 RCTs, RR leaving the study early 0.91 CI 0.36 to 2.33). Another study (n=31) comparing two types of omega-3 EFA's, ecisapentenoic acid enriched oil and docosahexanoic acid oil, also found no differences between these two EFA's in measures of mental state. One small (n=16) study investigated the effects of an omega-6 EFA compared with placebo for tardive dyskinesia and found no clear effects. There is not a clear dose response to omega-3 supplementation. Adverse effects seem rare but diarrhoea may be a problem in the medium term. REVIEWER'S CONCLUSIONS: The use of omega-3 polyunsaturated fatty acids for schizophrenia remains experimental and large well designed, conducted and reported studies are indicated and needed.


Jindrichova, S., O. Novakova, et al. (2003). "Corticosteroid effect on Caco-2 cell lipids depends on cell differentiation." J Steroid Biochem Mol Biol 87(2-3): 157-165.

            Previous studies from our laboratory have indicated that secondary hyperaldosteronism affects phospholipids of rat colonic enterocytes. To assess whether this represents a direct effect of mineralocorticoids on enterocytes, the role of aldosterone and dexamethasone in the regulation of lipid metabolism was examined in Caco-2 cells during development of their enterocyte phenotype. Differentiation of Caco-2 cells was associated with increased levels of triglycerides (TG) and cholesteryl esters (CE), a decreased content of cholesterol and phospholipids and changes in individual phospholipid classes. The phospholipids of differentiated cells had a higher content of n-6 polyunsaturated fatty acids (PUFA) and lower amounts of monounsaturated (MUFA) and saturated fatty acids than subconfluent undifferentiated cells. Differentiated cells exhibited a higher ability to incorporate [3H]arachidonic acid (AA) into cellular phospholipids and a lower ability for incorporation into TG and CE. Incubation of subconfluent undifferentiated cells with aldosterone or dexamethasone was without effect on the content of lipids, their fatty acids and [3H]AA incorporation. In contrast, aldosterone treatment of differentiated cells diminished the content of TG, increased the content of phospholipids and modulated their fatty acid composition. The percentage of n-6 and n-3 PUFA in phospholipids was increased and that of MUFA decreased, whereas no changes in TG were observed. The incorporation of [3H]AA into phospholipids was increased and into TG decreased and these changes were blocked by spironolactone. Treatment of differentiated cells with dexamethasone increased their CE content but no effect was identified upon other lipids, their fatty acid composition and on the incorporation of [3H]AA. As expected for the involvement of corticosteroid hormones the mineralocorticoid and glucocorticoid receptors were identified in Caco-2 cells by RT-PCR. The results suggest that aldosterone had a profound influence on lipid metabolism in enterocytes and that its effect depends on the stage of differentiation. The aldosterone-dependent changes occurring in phospholipids and their fatty acid composition may reflect a physiologically important phenomenon with long-term consequences for membrane structure and function.


Jiang, W. G., A. Douglas-Jones, et al. (2003). "Expression of peroxisome-proliferator activated receptor-gamma (PPARgamma) and the PPARgamma co-activator, PGC-1, in human breast cancer correlates with clinical outcomes." Int J Cancer 106(5): 752-7.

            Peroxisome-proliferator activated receptor-gamma (PPARgamma) belongs to a family of nuclear receptors and acts as receptor for peroxisome-proliferators, steroids, retinoic acids, and polyunsaturated fatty acids. Our study examined the transcript levels of peroxisome-proliferator activated receptor-gamma (PPARgamma) and its co-activator (PGC-1) in a cohort of patients with breast cancer. An invasive breast cancer cell, MDA MB 231 exhibited lower level of expression of PPARgamma, compared to non-invasive MCF-7. Breast cancer tissues (n = 120) exhibited a lower level of PPARgamma mRNA compared to normal tissues (n = 25, p = 0.05). No difference, however, was seen with PGC-1. Although the levels of PPARgamma and PGC-1 did not correlate with nodal involvement and grade, significantly lower levels of PPARgamma were seen in TNM3 and TNM4 tumors and from patients with local recurrence and those who died of breast cancer. Lowest level of PGC-1 was also seen in TNM3 and TNM4 tumors and patients who died of breast cancer. We conclude that there is aberrant expression of PPARgamma and its co-activator, PGC-1, in human breast cancer and low levels of these molecules in cancer tissues are associated with poor clinical outcomes.


Jayasinghe, C., N. Gotoh, et al. (2003). "Variation in lipid classes and fatty acid composition of salmon shark (Lamna ditropis) liver with season and gender." Comp Biochem Physiol B Biochem Mol Biol 134(2): 287-95.

            The influence of season and gender on lipid content, lipid classes, and fatty acid compositions was assessed in livers of salmon shark (Lamna ditropis), caught in the Pacific Ocean. No significant difference in the hepatosomatic index was noted with season, though the lipid content was significantly higher (P<0.05) in winter. Triacylglycerol (TAG) was identified as the predominant lipid class (78.5-82.0%), followed by sterol esters (5.7-9.1%) and hydrocarbons (3.4-5.4%). No significant differences were observed in TAG composition with respect to the season or gender. However, diacylglyceryl ether contents were significantly higher (P<0.05) in winter (3.8-5.3%) than those obtained in summer (1.3-1.1%). Polyunsaturated fatty acids constituted the major fatty acid class of salmon shark total liver lipid and docosahexaenoic acid (C22:6n-3) (22.7-28.4%) was the most abundant fatty acid which was significantly lower (P<0.05) in winter. These results suggested that lipid characteristics of salmon shark liver were influenced by season, but not by gender.


Iusupova, G. I., T. V. Fedichkina, et al. (2003). "[Sources of lipids in parenteral and enteral nutrition]." Vopr Pitan 72(3): 32-5.

            The review is devoted to sources of lipids in enteral and parenteral nutrition. The role of omega-3 and omega polyunsaturated fatty acids in metabolism of some lipid mediators is examined.


Itakura, K. and K. Uchida (2003). "Reaction of N(alpha)-hippuryllysine with 2-hydroxyheptanal: a model for lysine-directed protein modifications by lipid peroxidation." Chem Phys Lipids 124(2): 81-8.

            2-Hydroxyheptanal (2-HH) is one of the major aldehydes derived from peroxidation of polyunsaturated fatty acids. In the present study, to obtain an insight into the contributions of 2-HH to protein modifications during lipid peroxidation, a lysine-containing dipeptide, N(alpha)-hippuryllysine (N-benzoylglycyl-L-lysine, BGL), was reacted with 2-HH at neutral pH. The products were characterized on the basis of LC/MS and NMR spectroscopy. The reaction afforded a 2:1 2-HH-lysine adduct, 1-[5-(N-benzoylglycylamino)-5-carboxypentyl]-4-butyl-5-pentyl-1,2,6-trihyd ropyridin-3-one (I). In addition, we obtained a 1:1 2-HH-lysine adduct, N-[5-(N-benzoylglycylamino)-5-carboxypentyl]-1-amino-2-heptanone (III). The treatment of the purified III with 2-HH produced I. On the other hand, when the reaction mixture was allowed prolonged standing, I was slowly oxidized to 1-[5-(N-benzoylglycylamino)-5-carboxypentyl]-4-butyl-5-pentyl-3-hydroxypyr idinium (V). This conversion was strongly accelerated by the addition of copper(II) ion and 2,2'-bipyridyl. We propose here that the above series of conversions is the main pathway for the modification of lysine residues of proteins by 2-HH.


Itakura, K., A. Furuhata, et al. (2003). "Maillard reaction-like lysine modification by a lipid peroxidation product: immunochemical detection of protein-bound 2-hydroxyheptanal in vivo." Biochem Biophys Res Commun 308(3): 452-7.

            2-Hydroxyheptanal (2-HH) is one of the reactive aldehyde species generated during the peroxidation of n-6 polyunsaturated fatty acids, such as linoleic and arachidonic acids. Analogous to the Maillard reaction of reducing sugars, 2-HH readily reacts with lysine epsilon-amino groups. In the present study, to define the occurrence of the Maillard reaction-like lysine modification by 2-HH in vivo, we raised a monoclonal antibody directed to a trihydropyridinone (THPO) structure, 1-alkyl-4-butyl-5-pentyl-1,2,6-trihydropyridin-3-one, formed from 2-HH and lysine, and examined the presence of the antigenic structure in the human atherosclerotic aorta. Mice were immunized with the 2-HH-modified keyhole limpet hemocyanin (KLH) as the immunogen. Using a THPO-carrier protein conjugate, we screened the hybridomas and finally obtained a clone that produced the monoclonal antibody 3C8 (mAb3C8). The antibody strongly recognized bovine serum albumin (BSA) treated with 2-HH, but showed no cross-reactivity with BSAs modified with other related aldehydes. By using this antibody, it was revealed that the antigenic structure was indeed present in atherosclerotic lesions of the human aorta.


Isaev, V. A., R. A. Danilova, et al. (2003). "[Administration of the omega-3 polyunsaturated fatty acid drug eiferol decreases alcohol motivation in albino rats by elevating the level of antibodies to alcohol dehydrogenase]." Patol Fiziol Eksp Ter(1): 21-3.

            The study experimentally assessed the approach proposed by the authors to lower alcohol motivation, which involves enhancement of a specific immunity at the stage of alcoholization when acetaldehydemodified ethanol exchange enzymes [alcohol dehydrogenase (ADH)] and acetaldehyde dehydrogenase may be expected to occur. Omega-3 polyunsaturated fatty acid (PUFA) drugs enhance the formation of autoantibodies to modified ADH and decrease the activity of ADH in the stomach and liver. At the same time, PUFA drugs can, under certain conditions, produce an anti-alcoholic activity and a positive effect on the psychoemotional status of animals after the ethanol deprivation period.


Irons, R., M. J. Anderson, et al. (2003). "Dietary fish oil impairs primary host resistance against Listeria monocytogenes more than the immunological memory response." J Nutr 133(4): 1163-9.

            The primary objective of this study was to determine whether dietary (n-3) polyunsaturated fatty acids (PUFA) impair the ability of mice to generate an immunological memory response against the bacterial pathogen, Listeria monocytogenes. Weanling BALB/c female mice were fed for 28 d one of two semipurified high fat diets containing either lard or refined menhaden fish oil, rich in long-chain (n-3) PUFA. Mice were immunized with 10(4) or 10(3) colony forming units (cfu) bacteria. Thirty-five days later, these immune mice and age-matched naive (i.e., unimmunized) mice were challenged with 10(5) cfu bacteria. Three days postchallenge, bacterial clearance was determined. Compared with lard-fed mice, naive mice in the fish oil treatment group had higher bacterial loads in their liver and spleen (P < 0.001). When mice were immunized with 10(4) cfu bacteria before rechallenge with 10-fold more bacteria, both lard- and fish oil-fed mice had significantly lower bacterial loads in their liver and spleen (e.g., approximately 2 log(10); P < 0.001) compared with their naive counterparts. However, when the immunization dose was reduced to 10(3) bacteria, a modest diet treatment effect was observed, such that compared with immune lard-fed mice, immune fish oil-fed mice had significantly greater bacterial loads in their liver and spleen (i.e., approximately 0.5 log(10); P < 0.01). These data demonstrate for the first time that although dietary (n-3) PUFA can significantly impair host resistance to a primary as well as a secondary L. monocytogenes infection, the impairment of the immunological memory response is much less severe.


Innis, S. M. and S. L. Elias (2003). "Intakes of essential n-6 and n-3 polyunsaturated fatty acids among pregnant Canadian women." Am J Clin Nutr 77(2): 473-8.

            BACKGROUND: Fetal growth requires n-3 docosahexaenoic acid (DHA), which is derived from the essential n-3 fatty acids in the maternal diet. DHA is accumulated in the developing brain and is critical for normal neural and visual function. Available estimates suggest that 67 mg DHA/d is accumulated by the fetus during the third trimester of gestation. Little is known about n-3 fatty acid intakes in pregnant women, although human milk concentrations of DHA have decreased in recent years. OBJECTIVE: We prospectively determined the n-3 and n-6 fatty acid intakes of 55 pregnant Canadian women. DESIGN: A food-frequency questionnaire was completed at 28 and 35 wk, and plasma n-3 and n-6 fatty acids were measured at 35 wk gestation. The fatty acid composition of approximately 500 foods was analyzed to allow analysis of dietary intakes from specific foods. RESULTS: Intakes, as a percentage of energy, were (macro x +/- SEM) total fat, 28.0 +/- 3.6%; saturated fat, 9.8 +/- 0.3%; monounsaturated fat, 11.2 +/- 0.4%; polyunsaturated fat, 4.7 +/- 0.2%; linoleic acid, 3.9 +/- 0.2%; and alpha-linolenic acid, 0.54 +/- 0.05%. The daily intakes (range) were 160 +/- 20 (24-524) mg DHA/d, 121 +/- 8 (15-301) mg arachidonic acid/d, and 78 +/- 2 (4-125) mg eicosapentaenoic acid/d. The plasma phospholipids had (mg/100 g fatty acid) 5.0 +/- 0.18 DHA, 8.7 +/- 0.18 arachidonic acid, and 0.52 +/- 0.32 eicosapentaenoic acid. CONCLUSION: The low intake of DHA among some pregnant women highlights the need for studies to address the functional significance of maternal fat intakes during pregnancy on fetal development.


Innis, S. M. (2003). "Perinatal biochemistry and physiology of long-chain polyunsaturated fatty acids." J Pediatr 143(4 Suppl): S1-8.

            Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are important structural components of the central nervous system. These fatty acids are transferred across the placenta, are present in human milk, and are accumulated in the brain and retina during fetal and infant development. The high concentrations of DHA in the retina and of DHA and ARA in brain gray matter suggests that these fatty acids have important roles in retinal and neural function. Animal studies have shown that depletion of DHA from the retina and brain results in reduced visual function and learning deficits. The latter effects may be explained by changes in the membrane bilayer that alter membrane-associated receptors and signal transduction systems, ion channel activity, or direct effects on gene expression. DHA can be formed in the liver from alpha linolenic acid, but it is unclear if the rate of DHA synthesis in humans is sufficient to support optimal brain and retinal development. Although there is no evidence that the ability to form ARA from linoleic acid is limiting, supplementation with DHA reduces tissue ARA, possibly creating a conditional need for ARA in infants with a dietary intake of DHA. The amount of DHA in human milk varies widely and is positively correlated with visual and language development in breast-fed infants. Advances in understanding essential fatty acid requirements will benefit from intervention studies that use functionally relevant tests to probe the deficiency or adequacy of physiologically important pools of DHA and ARA in developing infants.


Imre, T., F. Zsila, et al. (2003). "Electrospray mass spectrometric investigation of the binding of cis-parinaric acid to bovine beta-lactoglobulin and study of the ligand-binding site of the protein using limited proteolysis." Rapid Commun Mass Spectrom 17(22): 2464-70.

            The binding property of parinaric acid, a polyunsaturated fatty acid, to bovine beta-lactoglobulin, has been studied by electrospray ionization mass spectrometry. Stable complexation was observed under acidic conditions in a molar ratio of 1:1. Competitive complexation experiments were performed using saturated and unsaturated fatty acid standards with different chain lengths and number of double bonds to study the specificity of the interaction. It can be concluded that formation of the parinaric acid-lactoglobulin complex is preferred even if the molar concentration of the other fatty acids is ten times higher. In cases of specific complex formation the protein must have an active site that is a good acceptor for the ligand molecule. Limited trypsinolysis was performed on the lactoglobulin molecule to identify which part is responsible for the complexation. An intermediate tryptic fragment with molecular mass of 5200 Da was found to have the same ability to bind parinaric acid as the intact protein. This disulfide-bonded residue, [41-70]S-S[149-162], might thus be involved in the specific complexation of parinaric acid to beta-lactoglobulin. This conclusion is consistent with previous information on this binding site.


Iizuka, T., Y. Jojima, et al. (2003). "Plesiocystis pacifica gen. nov., sp. nov., a marine myxobacterium that contains dihydrogenated menaquinone, isolated from the Pacific coasts of Japan." Int J Syst Evol Microbiol 53(Pt 1): 189-95.

            Two strains of a novel myxobacterium (designated SIR-1T and SHI-1) were isolated from Japanese coasts located in the Pacific subtropical zone. Cells of both strains were Gram-negative, rod-shaped and motile by gliding. The strains were chemoheterotrophic and strictly aerobic. They had the common characteristics associated with myxobacteria, such as bacteriolytic action and fruiting-body formation. The characteristic feature of the strains was a NaCl growth requirement with an optimum concentration of 2.0-3.0 % (w/v), comparable to that of sea water. In addition, other cationic components of sea water, such as Mg2+, Ca2+ and K+, were needed for growth. The major respiratory quinone was MK-8(H2). The cellular fatty acid profile was characterized by the predominance of iso-C15:0. Characteristic fatty acids anteiso-C16:0 and anteiso-C17:0, and a long-chain polyunsaturated fatty acid (C20:4), were also detected. The G + C content of the genomic DNA of strains SIR-1T and SHI-1 was between 69.3 and 70.0 mol% (as determined by HPLC). Strains SIR-1T and SHI-1 shared almost identical 16S rDNA sequences, and clustered with the genus Nannocystis as their closest relative upon phylogenetic analysis. However, the phylogenetic distance between the novel strains and the genus Nannocystis was large enough to warrant their different generic allocation. This finding was supported by significant phenotypic differences between the novel strains and Nannocystis. Thus, strains SIR-1T and SHI-1 represent a novel genus and species, for which the names Plesiocystis and Plesiocystis pacifica, respectively, are proposed. The type strain of the species is SIR-1T (=JCM 11591T =DSM 14875T =AJ 13960T).


Ibrahim, W. H., N. Bailey, et al. (2003). "Effects of carnitine and taurine on fatty acid metabolism and lipid accumulation in the liver of cats during weight gain and weight loss." Am J Vet Res 64(10): 1265-77.

            OBJECTIVE: To determine the effects of carnitine (Ca) or taurine (Ta) supplementation on prevention of lipid accumulation in the liver of cats. ANIMALS: 24 adult cats. PROCEDURE: Cats were fed a weight-gaining diet sufficient in n-6 polyunsaturated fatty acids (PUFAs), low in long-chain n-3 PUFAs (n-3 LPUFA), and containing corn gluten for 20 weeks. Cats gained at least 30% in body weight and were assigned to 4 weight-reduction diets (6 cats/diet) for 7 to 10 weeks (control diet, control plus Ca, control plus Ta, and control plus Ca and Ta). RESULTS: Hepatic lipids accumulated significantly during weight gain and weight loss but were not altered by Ca orTa after weight loss. Carnitine significantly increased n-3 and n-6 LPUFAs in hepatic triglycerides, decreased incorporation of 13C palmitate into very-low-density lipoprotein and hepatic triglycerides, and increased plasma ketone bodies. Carnitine also significantly increased weight loss but without altering the fat to lean body mass ratio. Taurine did not significantly affect any variables. Diets low in n-3 LPUFAs predisposed cats to hepatic lipidosis during weight gain, which was further exacerbated during weight loss. Mitochondrial numbers decreased during weight gain and weight loss but were not affected by treatment. Carnitine improved fatty acid oxidation and glucose utilization during weight loss without correcting hepatic lipidosis. CONCLUSIONS AND CLINICAL RELEVANCE: The primary mechanism leading to hepatic lipidosis in cats appears to be decreased fatty acid oxidation. Carnitine may improve fatty acid oxidation but will not ameliorate hepatic lipidosis in cats fed a diet low in n-3 fatty acids.


Iacazio, G. (2003). "Easy access to various natural keto polyunsaturated fatty acids and their corresponding racemic alcohols." Chem Phys Lipids 125(2): 115-21.

            Various optically active hydroxy derivatives of polyunsaturated fatty acids were easily oxidised to their corresponding keto derivatives using Dess-Martin periodinane. The reaction was run on the millimolar scale with good yields and without appreciable isomerisation of the surrounding double bonds. Reduction of these keto compounds to yield back the starting alcohols, but now as racemic mixtures, was also conducted using CeCl(3)-NaBH(4), once again without noticeable modification of the stereochemistry of the double bonds. These reactions proved the usefulness of the chemoenzymatic access to oxylipins through the use of lipoxygenases with various regiospecificity, combined with chemical transformations of the formed hydro(pero)xides.


Hwang, J. H., S. Bluml, et al. (2003). "In vivo characterization of fatty acids in human adipose tissue using natural abundance 1H decoupled 13C MRS at 1.5 T: clinical applications to dietary therapy." NMR Biomed 16(3): 160-7.

            Natural abundance proton-decoupled (13)C magnetic resonance spectroscopy was used to establish the in vivo lipid composition of normal adipose tissue and the corresponding effects of altered lipid diets. Experiments were performed on a standard 1.5 T clinical MR scanner using a double-tuned (1)H-(13)C coil. Peaks from double-bonded and methylene carbons were analyzed. Normal lipid composition was established in 20 control subjects. For comparison, five subjects on altered lipid diets were studied. Four subjects were on a fish oil supplement diet or predominantly seafood diet (polyunsaturated fatty acids), and one subject was on a Lorenzo's oil diet (monounsaturated fatty acids). Well-resolved (13)C spectra were obtained from the calf adipose tissue with a total acquisition time of 10 min. Model oil solutions were used to identify specific (13)C resonances. Subjects on lipid diets showed significantly elevated levels of monounsaturated and polyunsaturated fatty acids for Lorenzo's and fish oil diets, respectively. We conclude that (13)C MR spectroscopy can readily detect changes in lipid composition due to medium- and long-term therapeutic lipid diets. Since the examination is rapid, robust and noninvasive, opportunities arise for large clinical trials of preventive or therapeutic diets to be performed with (13)C MRS on a clinical MR scanner.


Hung, H. C., W. Willett, et al. (2003). "Tooth loss and dietary intake." J Am Dent Assoc 134(9): 1185-92.

            BACKGROUND: Several studies have reported that impaired dentition status is associated with poor nutritional intake. However, most of these studies are cross-sectional and thus are unable to clarify the temporal sequence. METHODS: We assessed the longitudinal relation between tooth loss and changes in consumption of fruits and vegetables and of nutrients important for general health among 31,813 eligible male health professionals. RESULTS: Subjects who lost five or more teeth had a significantly smaller reduction in consumption of dietary cholesterol and vitamin B12, greater reduction in consumption of polyunsaturated fat and smaller increase in consumption of dietary fiber and whole fruit than did subjects who had lost no teeth. Men who had lost teeth also were more likely to stop eating apples, pears and raw carrots. CONCLUSIONS: The results support the temporal association between tooth loss and detrimental changes in dietary intakes, which could contribute to increased risk of developing chronic diseases. PRACTICE IMPLICATIONS: Dietary evaluation and recommendations can be incorporated into dental visits to provide a greater benefit to patients.


Huang, Y., M. C. Torres, et al. (2003). "Regioselective synthesis of 1,N(2)-etheno-2'-deoxyguanosine and its generation in oligomeric DNA." Chem Res Toxicol 16(6): 708-14.

            Chloroethylene oxide and chloroacetaldehyde, reactive intermediates derived from vinyl chloride, and the epoxy-hydroxy-alkanals, produced endogenously in the metabolism of polyunsaturated fatty acids, react with nucleic acid bases in DNA to form exocyclic etheno derivatives of 2'-deoxyadenosine, 2'-deoxyguanosine, and 2'-deoxycytidine. This paper describes an efficient method for the synthesis of the exocyclic 1,N(2)-etheno adduct of 2'-deoxyguanosine and its incorporation into DNA oligomers using automated synthesis techniques. The synthesis was initiated by a high-yield alkylation of N(2)-protected 2'-deoxyguanosine at the 1-position with 1,2-diacetoxy-3-bromopropane. The product was converted to the 5'-O-dimethoxytrityl-3'-O-phosphoramidite using published techniques and incorporated site specifically into DNA oligomers with 99% coupling efficiency. Ring closure to yield the 6-hydroxyethano derivative was accomplished by oxidation with sodium periodate, and facile dehydration then afforded DNA oligomers containing 1,N(2)-etheno-2'-deoxyguanosine. All oligomers were characterized fully by physicochemical methods.


Huang, J., T. Aki, et al. (2003). "Grouping newly isolated docosahexaenoic acid-producing thraustochytrids based on their polyunsaturated fatty acid profiles and comparative analysis of 18S rRNA genes." Mar Biotechnol (NY) 5(5): 450-7.

            Seven strains of marine microbes producing a significant amount of docosahexaenoic acid (DHA; C22:6, n-3) were screened from seawater collected in coastal areas of Japan and Fiji. They accumulate their respective intermediate fatty acids in addition to DHA. There are 5 kinds of polyunsaturated fatty acid (PUFA) profiles which can be described as (1) DHA/docosapentaenoic acid (DPA; C22:5, n-6), (2) DHA/DPA/eicosapentaenoic acid (EPA; C20:5, n-3), (3) DHA/EPA, (4) DHA/DPA/EPA/arachidonic acid (AA; C20:4, n-6), and (5) DHA/DPA/EPA/AA/docosatetraenoic acid (C22:4, n-6). These isolates are proved to be new thraustochytrids by their specific insertion sequences in the 18S rRNA genes. The phylogenetic tree constructed by molecular analysis of 18S rRNA genes from the isolates and typical thraustochytrids shows that strains with the same PUFA profile form each monophyletic cluster. These results suggest that the C20-22 PUFA profile may be applicable as an effective characteristic for grouping thraustochytrids.


Hu, H. and K. Gao (2003). "Optimization of growth and fatty acid composition of a unicellular marine picoplankton, Nannochloropsis sp., with enriched carbon sources." Biotechnol Lett 25(5): 421-5.

            A unicellular marine picoplankton, Nannochloropsis sp., was grown under CO2-enriched photoautotrophic or/and acetate-added mixotrophic conditions. Photoautotrophic conditions with enriched CO2 of 2800 microl CO2 l(-1) and aeration gave the highest biomass yield (634 mg dry wt l(-1)), the highest total lipid content (9% of dry wt), total fatty acids (64 mg g(-1) dry wt), polyunsaturated fatty acids (35% total fatty acids) and eicosapentaenoic acid (EPA, 20:5omega3) (16 mg g(-1) dry wt or 25% of total fatty acids). Mixotrophic cultures gave a greater protein content but less carbohydrates. Adding sodium acetate (2 mM) decreased the amounts of the total fatty acids and EPA. Elevation of CO2 in photoautotrophic culture thus enhances growth and raises the production of EPA in Nannochloropsis sp.


Hu, F. B. (2003). "Plant-based foods and prevention of cardiovascular disease: an overview." Am J Clin Nutr 78(3 Suppl): 544S-551S.

            Evidence from prospective cohort studies indicates that a high consumption of plant-based foods such as fruit and vegetables, nuts, and whole grains is associated with a significantly lower risk of coronary artery disease and stroke. The protective effects of these foods are probably mediated through multiple beneficial nutrients contained in these foods, including mono- and polyunsaturated fatty acids, n-3 fatty acids, antioxidant vitamins, minerals, phytochemicals, fiber, and plant protein. In dietary practice, healthy plant-based diets do not necessarily have to be low in fat. Instead, these diets should include unsaturated fats as the predominant form of dietary fat (eg, fats from natural liquid vegetable oils and nuts), whole grains as the main form of carbohydrate, an abundance of fruit and vegetables, and adequate n-3 fatty acids. Such diets, which also have many other health benefits, deserve more emphasis in dietary recommendations to prevent chronic diseases.


Hsu, J. M. and S. T. Ding (2003). "Effect of polyunsaturated fatty acids on the expression of transcription factor adipocyte determination and differentiation-dependent factor 1 and of lipogenic and fatty acid oxidation enzymes in porcine differentiating adipocytes." Br J Nutr 90(3): 507-13.

            Polyunsaturated fatty acids (FA) regulate genes involved in lipid metabolism. The effects of polyunsaturated FA on the transcription factor adipocyte determination and differentiation-dependent factor (ADD) 1 and fatty acid synthase (FAS) mRNA in differentiating porcine adipocytes were measured using a stromal vascular cell culture system. Porcine stromal vascular cells were isolated from subcutaneous adipose tissues and plated in Dulbecco's modified Eagle's medium (DMEM)-nutrient mixture F-12 Ham (F-12) plus fetal bovine serum (100 ml/l) for 24 h. Then cells were differentiated in DMEM-F12 plus insulin, hydrocortisone and transferrin without or with polyunsaturated FA at 6.25, 25.00 or 100.00 microM. The ADD1 mRNA was decreased by 100.00 microM-arachidonic acid, 6.25 to 100.00 microM-docosahexaenoic acid or cis-9,trans-11-conjugated linoleic acid. The polyunsaturated FA reduced the transcription rate of FAS, but not of ADD1. All three polyunsaturated FA accelerated degradation of ADD1 and FAS mRNA to reduce the abundance of ADD1 and FAS mRNA. Results also showed that polyunsaturated FA inhibit the ADD1 expression, not only of mRNA concentration, but also of mature ADD1 protein concentration, suggesting an overall reduction of ADD1 function by polyunsaturated FA. Our present experiments demonstrate that polyunsaturated FA regulate the gene expression of ADD1 and enzymes involved in lipid metabolism in porcine adipocytes.


Houdali, B., H. G. Wahl, et al. (2003). "Glucose oversupply increases Delta9-desaturase expression and its metabolites in rat skeletal muscle." Diabetologia 46(2): 203-12.

            AIM/HYPOTHESIS: Previous studies have shown that prolonged glucose infusion causes insulin resistance and triglyceride accumulation in rat skeletal muscle. In this study, we investigated a possible relationship between insulin resistance and the composition of different accumulated lipid fractions in rat skeletal muscle. METHODS: Continuous glucose infusion was carried out in rats for 7 days. Lipids were extracted from skeletal muscle, separated by thin layer chromatography and fatty acid composition of phospholipids, triglycerides, diglycerides, free fatty acids and cholesterol esters fractions was analysed by gas chromatography. Delta9-Desaturase mRNA was measured by real time polymerase chain reaction. The enzyme activity was measured in the microsomal fractions. RESULTS: Prolonged glucose infusion (5 days) increased the relative content of palmitoleic acid (16:1 N7) several-fold (2.3- to 5.8-fold) in four out of five lipid fractions and enhanced oleic acid (18:1 N9) two-fold in three lipid fractions suggesting increased Delta9-desaturase activity while the content of several polyunsaturated fatty acids was reduced. In parallel, Delta9-Desaturase mRNA contents and enzyme activities in skeletal muscle were increased 10-fold, 75-fold, 2.6-fold and 7.7-fold after 2 and 5 days of glucose infusion, respectively. CONCLUSION/INTERPRETATION: Our results suggest that long-term glucose oversupply induces a rapid increase in Delta9-desaturase expression and enzyme activity in skeletal muscle which leads to fast and specific changes in fatty acid metabolism possibly contributing to the insulin resistance in this animal model.


Honen, B. N., D. A. Saint, et al. (2003). "Suppression of calcium sparks in rat ventricular myocytes and direct inhibition of sheep cardiac RyR channels by EPA, DHA and oleic acid." J Membr Biol 196(2): 95-103.

            The anti-arrhythmic effects of long-chain polyunsaturated fatty acids (PUFAs) may be related to their ability to alter calcium handling in cardiac myocytes. We investigated the effect of eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) on calcium sparks in rat cardiac myocytes and the effects of these PUFAs and the monounsaturated oleic acid on cardiac calcium release channels (RyRs). Visualization of subcellular calcium concentrations in single rat ventricular myocytes showed that intensity of calcium sparks was reduced in the presence of EPA and DHA (15 micro M). It was also found that calcium sparks decayed more quickly in the presence of EPA but not DHA. Sarcoplasmic vesicles containing RyRs were prepared from sheep hearts and RyR activity was determined by either [(3)H]ryanodine binding or by single-channel recording. Bilayers were formed from phosphatidylethanolamine and phosphatidylcholine dissolved in either n-decane or n-tetradecane. EPA inhibited [(3)H]ryanodine binding to RyRs in SR vesicles with K(I) = 40 micro M. Poly- and mono-unsaturated free fatty acids inhibited RyR activity in lipid bilayers. EPA (cytosolic or luminal) inhibited RyRs with K(I) =32 micro M and Hill coefficient, n(1) = 3.8. Inhibition was independent of the n-alkane solvent and whether RyRs were activated by ATP or Ca(2+). DHA and oleic acid also inhibited RyRs, suggesting that free fatty acids generally inhibit RyRs at micromolar concentrations.


Hogyes, E., C. Nyakas, et al. (2003). "Neuroprotective effect of developmental docosahexaenoic acid supplement against excitotoxic brain damage in infant rats." Neuroscience 119(4): 999-1012.

            Long-chain polyunsaturated fatty acid (LC-PUFA) composition of neural membranes is a key factor for brain development, in chemical communication of neurons and probably also their survival in response to injury. Viability of cholinergic neurons was tested during brain development following dietary supplementation of fish oil LC-PUFAs (docosahexaenoic acid [DHA], eicosapentaenoic acid, arachidonic acid) in the food of mother rats. Excitotoxic injury was introduced by N-methyl-D,L-aspartate (NMDA) injection into the cholinergic nucleus basalis magnocellularis of 14-day-old rats. The degree of loss of cholinergic cell bodies, and the extend of axonal and dendritic disintegration were measured following immunocytochemical staining of cell bodies and dendrites for choline acetyltransferase and p75 low-affinity neurotrophin receptor and by histochemical staining of acetylcholinesterase-positive fibres in the parietal neocortex. The impact of different feeding regimens on fatty acid composition of neural membrane phospholipids was also assayed at 12 days of age. Supplementation of LC-PUFAs resulted in a resistance against NMDA-induced excitotoxic degeneration of cholinergic neurones in the infant rats. More cholinergic cells survived, the dendritic involution of surviving neurons in the penumbra region decreased, and the degeneration of axons at the superficial layers of parietal neocortex also attenuated after supplementing LC-PUFAs. A marked increment in DHA content in all types of phospholipids was obtained in the forebrain neuronal membrane fraction of supplemented rats. It is concluded that fish oil LC-PUFAs, first of all DHA, is responsible for the neuroprotective action on developing cholinergic neurons against glutamate cytotoxicity.


Hirai, K., Y. Asano, et al. (2003). "[Reduction in n-3 PUFA levels and EPA/AA ratio in serum after desert travels in China]." Nippon Eiseigaku Zasshi 58(2): 275-80.

            OBJECTIVES: The effects of 3 months of desert travel in China on serum fatty acids and tocopherol were studied. METHODS: In project staff members (6 males, 3 females, aged 19-27 years), serum levels of fatty acids and alpha-tocopherol were analyzed before and after travel by gas liquid chromatography and high-performance liquid chromatography, respectively. RESULTS: Comparison of the levels before and after the trip showed no differences in serum total cholesterol, triglycerides, total protein or alpha-tocopherol. There were no changes in the levels of total fatty acids, while the percentage of polyunsaturated fatty acids increased (p < 0.05). Levels of n-3 PUFA lowered from 166 micrograms/ml to 103 micrograms/ml, and those of n-6 PUFA had increased from 988 micrograms/ml to 1140 micrograms/ml after the trip (p < 0.01 and p < 0.001, respectively). No change was observed in the serum levels of alpha-linolenic acid (C18:3n-3), but lowering of the levels of eicosapentaenoic acid (EPA, C20:5n-3) from 41.4 micrograms/ml to 16.3 micrograms/ml and docosahexaenoic acid (DHA, C22:6n-3) from 107.8 micrograms/ml to 71.7 micrograms/ml was found after the trip (p < 0.05 and p < 0.01, respectively). Serum levels of linoleic acid (LA, C18:2n-6) increased from 832 micrograms/ml to 598 micrograms/ml (p < 0.001), and arachidonic acid (AA, C20:4n-6) tended to increase. The ratios of n-3/n-6 PUFA and EPA/AA decreased from 0.171 to 0.091 and from 0.258 to 0.096 after the trip, respectively (p < 0.01 for both). CONCLUSIONS: Our findings indicated that 3 months of desert travel increased the serum levels of n-6 PUFA and LA and reduced the serum levels of n-3 PUFA and EPA and the ratios of n-3/n-6 PUFA and EPA/AA, possibly due to a relative essential fatty acid deficiency.


Hirafuji, M., T. Machida, et al. (2003). "Cardiovascular protective effects of n-3 polyunsaturated fatty acids with special emphasis on docosahexaenoic acid." J Pharmacol Sci 92(4): 308-16.

            It is widely accepted that n-3 polyunsaturated fatty acids (PUFAs) rich in fish oils protect against several types of cardiovascular diseases such as myocardial infarction, arrhythmia, atherosclerosis, or hypertension. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be the active biological components of these effects. Although the precise cellular and molecular mechanisms underlying the beneficial effects are still uncertain, the protective effects of n-3 PUFAs are attributable to their direct effects on vascular smooth muscle cell (VSMC) functions. These n-3 PUFAs activate K(+)(ATP) channels and inhibit certain types of Ca(2+) channels, probably via at least 2 distinct mechanisms. N-3 PUFAs favorably alter the eicosanoid profile and regulate cytokine-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 via mechanisms involving modulation of signaling transduction events. N-3 PUFAs also modulate VSMC proliferation, migration, and apoptosis. These recent data suggest that modulation of these VSMC functions contribute to the beneficial effects of n-3 PUFAs on various cardiovascular disorders. Furthermore, recent studies strongly suggest that DHA has more potent and beneficial effects than EPA. However, many questions about the cellular and molecular mechanisms still remain to be answered.


Higuchi, Y. (2003). "Chromosomal DNA fragmentation in apoptosis and necrosis induced by oxidative stress." Biochem Pharmacol 66(8): 1527-35.

            Chromosomal DNA dysfunction plays a role in mammalian cell death. Oxidative stress producing reactive oxygen species (ROS) induces chromatin dysfunction such as single- and double-strand DNA fragmentation leading to cell death through apoptosis or necrosis. More than 1 Mbp giant DNA, 200-800 or 50-300 kbp high molecular weight (HMW) DNA and internucleosomal DNA fragments are produced by oxidative stress and by some agents producing ROS during apoptosis or necrosis in several types of mammalian cells. Some nucleases involved in the chromosomal DNA fragmentation in apoptosis or necrosis are classified. ROS-mediated DNA fragmentation is caused and enhanced by polyunsaturated fatty acids (PUFAs) or their hydroperoxides through lipid peroxidation. A reduction of intracellular GSH levels induced by the inhibition of cystein transport or GSH biosynthesis leads to cell death through over production and accumulation of ROS in some types of mammalian cells. The ROS accumulation system has been used as a model of oxidative stress to discuss whether ROS-mediated DNA fragmentation associated with cell death is based on apoptosis or necrosis.


High, K. P., J. Sinclair, et al. (2003). "Advanced age, but not anergy, is associated with altered serum polyunsaturated fatty acid levels." J Nutr Health Aging 7(6): 378-84.

            Unknown factors present in the serum of older adults impair lymphocyte function and may be responsible for anergy (absence of delayed-type hypersensitivity (DTH)) present in many older adults. Polyunsaturated fatty acids (PUFAs) and their metabolites are immunomodulatory and may play a role in clinical conditions of advanced age, including immune dysfunction. We hypothesized that PUFAs could be the factor(s) present in serum that contribute to impaired immune responses in older adults. Prior studies of serum PUFAs in older adults neither adequately control dietary PUFA intake, nor investigated the relationship of PUFAs and DTH responses. We determined serum PUFA concentrations in young adults with normal immune responses, and older adults with impaired (anergic elderly) or normal immunity (nonanergic elderly) before and after administering a standardized diet. After controlling for dietary intake, advancing age was associated with markedly higher serum concentrations of arachidonic acid (AA), dihomo-gamma-linoleic acid (DGLA), and eicosapentaenoic acid (EPA) and a lower AA:EPA ratio. Other serum PUFAs and the AA:DGLA ratio were unaffected by age. However, there was no difference between older adults with or without anergy. These data suggest advanced age is associated with marked alterations of serum PUFAs that are only apparent after strictly controlling dietary intake. However, there was no association of serum PUFA concentrations with DTH status among older adults.


Hibbeln, J. R., K. K. Makino, et al. (2003). "Smoking, gender, and dietary influences on erythrocyte essential fatty acid composition among patients with schizophrenia or schizoaffective disorder." Biol Psychiatry 53(5): 431-41.

            BACKGROUND: Prior reports of decreased levels of essential fatty acids among schizophrenic patients have generated several hypotheses proposing inherent abnormalities in phospholipid and fatty acid metabolism and have provided the basis for treatment trials; however, these essential fatty acid aberrations may be attributable to uncontrolled factors, such as smoking, rather than abnormalities inherent to schizophrenia. METHODS: Erythrocyte fatty acid compositions were quantified in 72 medicated schizophrenic or schizoaffective patients both at baseline and after 16 weeks of supplementation with 3 g/day of either ethyl-eicosapentaenoic acid or placebo. Current smoking status, gender, dietary survey, and Montgomery Asburg Depression Rating Scale, Repeatable Battery for the Assessment of Neuropsychological Status, Abnormal Involuntary Movement Scale, and Positive and Negative Syndrome Scale scores were assessed. RESULTS: Schizophrenic patients who smoked had lower baseline erythrocyte docosahexaenoic acid percent (2.98 +/-.7 vs. 3.59 +/- 1.2, p <.005) and eicosapentaenoic acid (EPA) percent (.39 +/-.13 vs. 47 +/-.22, p <.05), compared with nonsmokers, with a significant gender interaction (p <.01) in multivariate analyses of variance. Baseline arachidonic acid did not differ. Smokers reported lower dietary intake (percent total fat) of linolenic acid (F = 10.1, p <.003) compared with nonsmokers. Nonsmoking women reported greater dietary intake of EPA compared with smoking men or nonsmokers of either gender. CONCLUSIONS: Smoking status, gender, and dietary intake significantly predicted erythrocyte polyunsaturated fatty acid status among schizophrenic patients. No evidence was found for subgroups of schizophrenia or relationships to specific symptom severity on the basis of erythrocyte fatty acids. Prior reports of abnormalities of essential fatty acid metabolism among schizophrenic patients may have been an artifact of patients' smoking behavior and differences in dietary intake of omega-3 fatty acids.


Heude, B., P. Ducimetiere, et al. (2003). "Cognitive decline and fatty acid composition of erythrocyte membranes--The EVA Study." Am J Clin Nutr 77(4): 803-8.

            BACKGROUND: Dietary factors might modify cognitive decline that results from aging. Fatty acids, which are limiting factors in brain development, are prime candidates. OBJECTIVE: We studied the relation between erythrocyte membrane fatty acid composition and cognitive decline in free-living volunteers. DESIGN: In 1995, erythrocyte membrane fatty acid composition was measured in 246 men and women (aged 63-74 y) from the Etude du Vieillissement Arteriel (EVA) cohort. During a 4-y follow-up, cognitive abilities were assessed longitudinally with the Mini-Mental State Examination. Moderate cognitive decline was defined as a > or = 2-point decrease over the 4 y. The predictive value of fatty acid proportions on cognitive decline was assessed with a multivariate logistic model that included age, sex, education level, and initial Mini-Mental State Examination score as covariates. RESULTS: Higher proportions of both stearic acid (saturated, 18:0) and total n-6 polyunsaturated fatty acids were associated with greater risk of cognitive decline; the odds ratios were 1.91 (95% CI: 1.16, 3.15) and 1.59 (95% CI: 1.04, 2.44), respectively, for 1-SD differences in fatty acid proportions. Conversely, a higher proportion of total n-3 fatty acids was associated with a lower risk of cognitive decline; the odds ratio was 0.59 (95% CI: 0.38, 0.93). CONCLUSIONS: The inverse association between cognitive decline and the ratio of n-3 to n-6 fatty acids in erythrocyte membranes agrees with results obtained in some studies that assessed fatty acid intake by using dietary questionnaires. These results require confirmation but provide new rationale for studying how these modifiable risk factors might be implicated in the cognitive aging process.


Helland, I. B., L. Smith, et al. (2003). "Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age." Pediatrics 111(1): e39-44.

            OBJECTIVES: Docosahexaenoic acid (DHA; 22:6 n-3) and arachidonic acid (AA; 20:4 n-6) are important for development of the central nervous system in mammals. There is a growth spurt in the human brain during the last trimester of pregnancy and the first postnatal months, with a large increase in the cerebral content of AA and DHA. The fetus and the newborn infant depend on maternal supply of DHA and AA. Our hypothesis was that maternal intake of DHA during pregnancy and lactation is marginal and that high intake of this fatty acid would benefit the child. We examined the effect of supplementing pregnant and lactating women with very-long-chain n-3 polyunsaturated fatty acids (PUFAs; cod liver oil) on mental development of the children, compared with maternal supplementation with long-chain n-6 PUFAs (corn oil). METHODS: The study was randomized and double-blinded. Pregnant women were recruited in week 18 of pregnancy to take 10 mL of cod liver oil or corn oil until 3 months after delivery. The cod liver oil contained 1183 mg/10 mL DHA, 803 mg/10 mL eicosapentaenoic acid (20:5 n-3), and a total of 2494 mg/10 mL summation operator n-3 PUFAs. The corn oil contained 4747 mg/10 mL linoleic acid (18:2 n-6) and 92 mg/10 mL alpha-linolenic acid (18:3 n-3). The amount of fat-soluble vitamins was identical in the 2 oils (117 micro g/mL vitamin A, 1 micro g/mL vitamin D, and 1.4 mg/mL dl-alpha-tocopherol). A total of 590 pregnant women were recruited to the study, and 341 mothers took part in the study until giving birth. All infants of these women were scheduled for assessment of cognitive function at 6 and 9 months of age, and 262 complied with the request. As part of the protocol, 135 subjects from this population were invited for intelligence testing with the Kaufman Assessment Battery for Children (K-ABC) at 4 years of age. Of the 135 invited children, 90 came for assessment. Six children did not complete the examination. The K-ABC is a measure of intelligence and achievement designed for children aged 2.5 years through 12.5 years. This multisubtest battery comprises 4 scales: Sequential Processing, Simultaneous Processing, Achievement (not used in the present study), and Nonverbal Abilities. The Sequential Processing and Simultaneous Processing scales are hypothesized to reflect the child's style of problem solving and information processing. Scores from these 2 scales are combined to form a Mental Processing Composite, which serves as the measure of intelligence in the K-ABC. RESULTS: We received dietary information from 76 infants (41 in the cod liver oil group and 35 in the corn oil group), documenting that all of them were breastfed at 3 months of age. Children who were born to mothers who had taken cod liver oil (n = 48) during pregnancy and lactation scored higher on the Mental Processing Composite of the K-ABC at 4 years of age as compared with children whose mothers had taken corn oil (n = 36; 106.4 [7.4] vs 102.3 [11.3]). The Mental Processing Composite score correlated significantly with head circumference at birth (r = 0.23), but no relation was found with birth weight or gestational length. The children's mental processing scores at 4 years of age correlated significantly with maternal intake of DHA and eicosapentaenoic acid during pregnancy. In a multiple regression model, maternal intake of DHA during pregnancy was the only variable of statistical significance for the children's mental processing scores at 4 years of age. CONCLUSION: Maternal intake of very-long-chain n-3 PUFAs during pregnancy and lactation may be favorable for later mental development of children.


Helge, J. W. and F. Dela (2003). "Effect of training on muscle triacylglycerol and structural lipids: a relation to insulin sensitivity?" Diabetes 52(8): 1881-7.

            We studied whether endurance training impacts insulin sensitivity by affecting the structural and storage lipids in humans. Eight male subjects participated (age 25 +/- 1 years, height 178 +/- 3 cm, weight 76 +/- 4 kg [mean +/- SE]). Single-leg training was performed for 30 min/day for 4 weeks at approximately 70% of single-leg maximal oxygen uptake. After 8, 14, and 30 days, a two-step hyperinsulinemic-euglycemic glucose clamp, combined with catheterization of an artery and both femoral veins, was performed. In addition, a muscle biopsy was obtained from vastus lateralis of both legs. Maximal oxygen uptake increased by 7% in the trained leg (T), and training workload increased (P < 0.05) from 79 +/- 12 to 160 +/- 15 W. At day 8, glucose uptake was higher (P < 0.01) in the trained (0.8 +/- 0.2, 6.0 +/- 0.8, 13.4 +/- 1.2 mg x min(-1) x kg(-1) leg wt) than the untrained leg (0.5 +/- 0.2, 3.7 +/- 0.6, 10.5 +/- 1.5 mg x min(-1) x kg(-1) leg wt) at basal and the two succeeding clamp steps, respectively. After day 8, training did not further increase leg glucose uptake. Individual muscle triacylglycerol fatty acid composition and total triacylglycerol content were not significantly affected by training and thus showed no relation to leg glucose uptake. Individual muscle phospholipid fatty acids were not affected by training, but the content of phospholipid polyunsaturated fatty acids was higher (P < 0.06) after 30 than 8 days in T. Furthermore, after 30 days of training, the sum of phospholipid long-chain polyunsaturates was correlated to leg glucose uptake (r = 0.574, P < 0.04). Endurance training did not influence muscle triacylglycerol content or total triacylglycerol fatty acid composition. In contrast, training induced a minor increase in the content of phospholipid fatty acid membrane polyunsaturates, which may indicate that membrane lipids may have a role in the training-induced increase in insulin sensitivity.


Healy, D. A., R. W. Watson, et al. (2003). "Polyunsaturated and monounsaturated fatty acids increase neutral lipid accumulation, caspase activation and apoptosis in a neutrophil-like, differentiated HL-60 cell line." Clin Sci (Lond) 104(2): 171-9.

            We report here that monounsaturated fatty acids and polyunsaturated fatty acids (PUFAs) provoke the accumulation of neutral lipids and apoptosis in retinoic acid-treated HL-60 cells in a concentration- and time-dependent manner. The PUFAs (arachidonic acid, docosahexanoic acid and eicosapentaenoic acid) provoked higher levels of HL-60 apoptosis compared with the monounsaturated oleic acid or the saturated palmitic acid. Cell size and granularity were also altered by fatty acid treatment. The PUFA-induced apoptosis was correlated with increased activity of caspase 3 and caspase 9. Lipid peroxidation was also increased in the presence of PUFAs, but was not responsible for activating cell apoptosis. Lipid derived metabolites may be responsible for activation of caspases and induction of cell apoptosis.


Havaux, M. (2003). "Spontaneous and thermoinduced photon emission: new methods to detect and quantify oxidative stress in plants." Trends Plant Sci 8(9): 409-13.

            Peroxidation of polyunsaturated fatty acids is one of the main events triggered by oxidative stress in cells. Some lipid peroxidation products are light-emitting species, and their luminescence can be used as an internal marker of oxidative stress. However, this spontaneous chemiluminescence is weak and difficult to measure. Recent studies have shown that an alternative approach that involves measuring thermoluminescence bands at high temperature (in the range 80-150 degrees C) is a simple way of detecting and quantifying lipid peroxidative damage and oxidative stress in plants.


Harris, W. S. (2003). "n-3 Long-chain polyunsaturated fatty acids reduce risk of coronary heart disease death: extending the evidence to the elderly." Am J Clin Nutr 77(2): 279-80.


Harel, M. and A. R. Place (2003). "Tissue essential fatty acid composition and competitive response to dietary manipulations in white bass (Morone chrysops), striped bass (M. saxatilis) and hybrid striped bass (M. chrysopsxM. saxatilis)." Comp Biochem Physiol B Biochem Mol Biol 135(1): 83-94.

            The effects of wide changes in dietary levels of docosahexaenoic (DHA) or arachidonic (ArA) acids on growth, survival and fatty acid composition in body tissues of Morone larvae were examined. White bass (WB, Morone chrysops), striped bass (SB, Morone saxatilis) and sunshine hybrid bass (HSB, M. chrysopsxM. saxatilis) larvae (day 24-46) were fed Artemia nauplii enriched with algal sources of varying proportions of DHA and ArA (from 0 to over 20% of total fatty acids). WB larvae fed DHA-deficient Artemia diet retarded over 50% of their potential growth, however, increasing dietary DHA/ArA ratios were associated with a significant growth improvement. The highest proportion of polyunsaturated fatty acids was found in WB neural tissue (approx. 50% of total fatty acids), while HSB neural tissue contained the highest proportion of saturated fatty acids (approx. 35% of total fatty acids). Within the neural tissues of all Morone larvae, both DHA and ArA were generally the most dominant as well as the most responding fatty acids to dietary manipulations (except in WB fed DHA or ArA deficient diets). HSB neural tissue was particularly efficient in retaining a significant amount of DHA in the face of dietary deficiency. However, WB neural tissue was the most responsive to dietary increase in DHA, accumulating a significantly higher amount of DHA (P<0.05) than SB or HSB. Results demonstrate significant differences in fatty acid composition and growth responsiveness to dietary manipulations between Morone larvae species and within specific tissues. WB weight gain and neural tissue composition was affected most by dietary changes in both DHA and ArA whereas SB and HSB tissue compositions were generally less affected by dietary manipulations.


Hardie, R. C. (2003). "Regulation of TRP channels via lipid second messengers." Annu Rev Physiol 65: 735-59.

            In Drosophila photoreceptors, the light-sensitive current is mediated downstream of phospholipase C by TRP (transient receptor potential) channels. Recent evidence suggests that Drosophila TRP channels are activated by diacylglycerol (DAG) or its metabolites (polyunsaturated fatty acids), possibly in combination with the reduction in phosphatidyl inositol 4,5 bisphosphate (PIP2). Consistent with this view, diacylglycerol kinase is identified as a key enzyme required for response termination. Signaling is critically dependent upon efficient PIP2 synthesis; mutants of this pathway in combination with genetically targeted PIP2 reporters provide unique insights into the kinetics and regulation of PIP2 turnover. Recent evidence indicates that a growing number of mammalian TRP homologues are also regulated by lipid messengers, including DAG, arachidonic acid, and PIP2.


Hardie, R. C., F. Martin, et al. (2003). "Rescue of light responses in the Drosophila "null" phospholipase C mutant, norpAP24, by the diacylglycerol kinase mutant, rdgA, and by metabolic inhibition." J Biol Chem 278(21): 18851-8.

            Light responses in Drosophila are reportedly abolished in severe mutants of the phospholipase C (PLC) gene, norpA. However, on establishing the whole-cell recording configuration in photoreceptors of the supposedly null allele, norpAP24, we detected a small ( approximately 15 pA) inward current that represented spontaneous light channel activity. The current decayed during approximately 20 min, after which tiny residual responses (<2 pA) were elicited by intense flashes. Both spontaneous currents and light responses appeared to be mediated by residual PLC activity, because they were enhanced by impairing diacylglycerol (DAG) kinase function by mutation (rdgA) or by restricting ATP but were reduced or abolished by a mutation of the PLC-specific Gq alpha subunit. It was reported recently that metabolic inhibition activated the light-sensitive transient receptor potential and transient receptor potential-like channels, even in norpAP24, leading to the conclusion that this action was independent of PLC (Agam, K., von Campenhausen, M., Levy, S., Ben-Ami, H. C., Cook, B., Kirschfeld, K., and Minke, B. (2000) J. Neurosci. 20, 5748-5755). However, we found that channel activation by metabolic inhibitors in norpAP24 was strictly dependent on the residual PLC activity underlying the spontaneous current, because the inhibitors failed to activate any channels after the spontaneous current had decayed. By contrast, polyunsaturated fatty acids invariably activated the channels independently of PLC. The results strongly support the obligatory requirement for PLC and DAG in Drosophila phototransduction, suggest that activation by metabolic inhibition is primarily because of the failure of diacylglycerol kinase, and are consistent with the proposal that polyunsaturated fatty acids, which are potential DAG metabolites, act directly on the channels.


Hardie, R. C. (2003). "TRP channels in Drosophila photoreceptors: the lipid connection." Cell Calcium 33(5-6): 385-93.

            The light-sensitive current in Drosophila photoreceptors is mediated by transient receptor potential (TRP) channels, at least two members of which (TRP and TRPL) are activated downstream of phospholipase C (PLC) in response to light. Recent evidence is reviewed suggesting that Drosophila TRP channels are activated by one or more lipid products of PLC activity: namely diacylglycerol (DAG), its metabolites (polyunsaturated fatty acids) or the reduction in phosphatidylinositol 4,5-bisphosphate (PIP(2)). The most compelling evidence for this view comes from analysis of rdgA mutants which are unable to effectively metabolise DAG due to a defect in DAG kinase. The rdgA mutation leads to constitutive activation of both TRP and TRPL channels and dramatically increases sensitivity to light in hypomorphic mutations of PLC and G protein.


Harbige, L. S. (2003). "Fatty acids, the immune response, and autoimmunity: a question of n-6 essentiality and the balance between n-6 and n-3." Lipids 38(4): 323-41.

            The essentiality of n-6 polyunsaturated fatty acids (PUFA) is described in relation to a thymus/thymocyte accretion of arachidonic acid (20:4n-6, AA) in early development, and the high requirement of lymphoid and other cells of the immune system for AA and linoleic acid (1 8:2n-6, LA) for membrane phospholipids. Low n-6 PUFA intakes enhance whereas high intakes decrease certain immune functions. Evidence from in vitro and in vivo studies for a role of AA metabolites in immune cell development and functions shows that they can limit or regulate cellular immune reactions and can induce deviation toward a T helper (Th)2-like immune response. In contrast to the effects of the oxidative metabolites of AA, the longer-chain n-6 PUFA produced by gamma-linolenic acid (18:3n-6, GLA) feeding decreases the Th2 cytokine and immunoglobulin (Ig)G1 antibody response. The n-6 PUFA, GLA, dihomo-gamma-linolenic acid (20:3n-6, DHLA) and AA, and certain oxidative metabolites of AA can also induce T-regulatory cell activity, e.g., transforming growth factor (TGF)-beta-producing T cells; GLA feeding studies also demonstrate reduced proinflammatory interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha production. Low intakes of long-chain n-3 fatty acids (fish oils) enhance certain immune functions, whereas high intakes are inhibitory on a wide range of functions, e.g., antigen presentation, adhesion molecule expression, Th1 and Th2 responses, proinflammatory cytokine and eicosanoid production, and they induce lymphocyte apoptosis. Vitamin E has a demonstrable critical role in long-chain n-3 PUFA interactions with immune functions, often reversing the effects of fish oil. The effect of dietary fatty acids on animal autoimmune disease models depends on both the autoimmune model and the amount and type of fatty acids fed. Diets low in fat, essential fatty acid deficient (EFAD), or high in long-chain n-3 PUFA from fish oils increase survival and reduce disease severity in spontaneous autoantibody-mediated disease, whereas high-fat LA-rich diets increase disease severity. In experimentally induced T cell-mediated autoimmune disease, EFAD diets or diets supplemented with long-chain n-3 PUFA augment disease, whereas n-6 PUFA prevent or reduce the severity. In contrast, in both T cell- and antibody-mediated autoimmune disease, the desaturated/elongated metabolites of LA are protective. PUFA of both the n-6 and n-3 families are clinically useful in human autoimmune-inflammatory disorders, but the precise mechanisms by which these fatty acids exert their clinical effects are not well understood. Finally, the view that all n-6 PUFA are proinflammatory requires revision, in part, and their essential regulatory and developmental role in the immune system warrants appreciation.


Harazono, K., Y. Watanabe, et al. (2003). "Trapping of 2,7-dichlorodibenzo-p-dioxin in aqueous solution by enzymatic reaction of fungal manganese peroxidase in the presence of polyunsaturated fatty acids." Curr Microbiol 47(3): 250-4.

            In the presence of polyunsaturated fatty acids, including cis-4,7,10,13,16,19-docosahexaenoic acid (DHA), 2,7-dichlorodibenzo-p-dioxin (DCDD) was treated with manganese peroxidase (MnP) from white rot basidiomycete Phanerochaete sordida YK-624. After incubation with MnP, DCDD could not be extracted from the reaction mixture with n-hexane and was trapped in the water layer. DCDD was released by alkalification of the water layer. DCDD was also trapped after treatment with lipoxidase, which produces hydroperoxides from unsaturated lipids. The amounts of thiobarbituric acid-reactive substances produced in the MnP reactions with three highly unsaturated fatty acids were higher than the amounts produced with three fatty acids with a lower degree of unsaturation. These results suggest that a DCDD-trapping compound may be produced by peroxidation of the polyunsaturated fatty acids.


Hamplova, B., O. Novakova, et al. (2003). "Effect of hypo- and hyperthyroid states on phospholipid composition in developing rat heart." Mol Cell Biochem 252(1-2): 295-303.

            The aim of this study was to examine the effect of hypo- and hyperthyroidism on the phospholipid composition in developing rat heart. The hypothyroid state (PTU) was induced by 0.05% 6-n-propyl-2-thiouracil in drinking water given to nursing mothers from the postnatal day 2-21. The hyperthyroidism (T3) was made by daily injection of 3,3',5-triiodo-L-thyronine (10 microg/100 g body wt) to newborns in the same time period. Age matched intact littermates were taken as euthyroid controls. PTU decreased the concentration of total phospholipids (PL), choline phosphoglycerides (PC), ethanolamine phosphoglycerides (PE) and diphosphatidylglycerol (DPG) and increased the proportion of plasmalogen component of PE (PLPE). T3 increased the concentration of PL, PC, PE, DPG and decreased PLPE in comparison with euthyroid controls. The ratio of saturated/unsaturated fatty acids (FA) in PE was decreased in PTU and increased in T3 group. The ratio of n-6/n-3 polyunsaturated FA in PC, PE and phosphatidylinositol (PI) was increased in PTU due to increase of 18:2n-6 and decrease of 22:6n-3 proportion. T3 decreased this ratio because of decline in 20:4n-6 and rise in 22:6n-3 proportion. Both hypo- and hyperthyroidism decreased the ratio of 20:4n-6/18:2n-6 in the majority of phospholipids. PTU decreased the unsaturation index in PC, PI and phosphatidylserine. It is concluded that thyroid state plays an essential role in the development of membrane phospholipid components in cardiac membranes during the early postnatal period.


Hakala, P., L. R. Knuts, et al. (2003). "Comparison of nutrient intake data calculated on the basis of two different databases. Results and experiences from a Swedish-Finnish study." Eur J Clin Nutr 57(9): 1035-44.

            BACKGROUND AND OBJECTIVE: In international surveys of food consumption and nutrient intake, it is essential that the dietary data are comparable when different databases and calculation programs are used. The aim of the present analysis was to examine the comparability of nutrient intake data calculated on the basis of the Swedish food composition database PC-kost and the Finnish food composition database Nutrica. SUBJECTS AND METHODS: A total of 20 male adults currently living in Sweden were selected from a group of Finnish twins of the Finnish Twin Cohort Study. Food consumption data were collected by means of diet history interviews. The estimated intakes of 30 nutrients calculated on the basis of PC-kost were compared to the corresponding estimates calculated on the basis of Nutrica. The calculation procedures were standardised. RESULTS: No statistically significant differences were observed in the mean intakes of energy, total fat, saturated fat, carbohydrates, dietary fibre, alcohol, cholesterol, vitamin A, retinol, beta-carotene, vitamin D, alpha-tocopherol, riboflavin, niacin, vitamin B(12), vitamin C or phosphorus. PC-kost yielded a 20% higher intake (NS) for vitamin D and 23% higher intake (P<0.001) for thiamine than Nutrica, which is mainly attributed to the differences in the enrichment of foodstuffs between Sweden and Finland. Conversely, PC-kost yielded 53% lower values (P<0.001) for selenium than Nutrica, owing to the increased selenium content in many Finnish foodstuffs as a result of the addition of selenium to fertilisers. Statistically significant differences were found for protein, monounsaturated fatty acids, vitamin B(6), iron and sodium (5-9% higher values from PC-kost) and for polyunsaturated fatty acids, folate, zinc, calcium, magnesium and potassium (4-10% lower values from PC-kost). The variation in the intake of these nutrients between the two methods may be explained by the differences in foodstuff-specific nutrient values (eg product formulations), or differences in the sources of data, recipes or calculation procedures.The correlation coefficient was > or =0.81 for most nutrients. At least 85% of the subjects in each PC-kost quintile were classified into the same or adjacent Nutrica quintile for all nutrients. CONCLUSIONS: Our results indicate that, for a dominant part of the examined nutrients, the estimated intakes calculated by means of standardised procedures using the PC-kost and Nutrica databases are comparable between Sweden and Finland. Differences observed for some nutrients reflect either actual differences in foods between the two countries or methodological differences in the assessment of nutrient intakes.


Hajjar, I. and T. Kotchen (2003). "Regional variations of blood pressure in the United States are associated with regional variations in dietary intakes: the NHANES-III data." J Nutr 133(1): 211-4.

            Compared with other regions in the United States, the southern region has had the highest stroke mortality rate and a more prevalent and resistant hypertension. We designed this analysis of the data obtained from the National Health and Nutritional Examination Survey III (NHANES-III), which is a community-based cross-sectional survey, to describe regional variations in blood pressure and the reported consumption of nutrients, focusing on those linked to blood pressure, in the United States. We selected the following variables from the NHANES-III data for this analysis: systolic and diastolic blood pressures, protein, carbohydrates, total fatty acids, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, cholesterol, fiber, sodium, potassium, calcium, magnesium, zinc, copper, iron, riboflavin, niacin, thiamin, alcohol and vitamins C, E, B-6 and B-12. Of the 17,752 participants in the survey who were 18 y of age or older, the south had the highest systolic and diastolic blood pressures (P < 0.005 for each) and reported the highest consumption of monounsaturated fatty acids, polyunsaturated fatty acids and cholesterol (P < 0.05 for all) and the least amount of fiber in the multivariate analysis (P < 0.005). The highest reported sodium consumption was in the south region (3.4 +/- 0.02 g), and the lowest was in the west (3.2 +/- 0.03 g; P < 0.05). The south also consumed the least potassium, calcium, phosphorous, magnesium, copper, riboflavin, niacin, iron and vitamins A, C and B-6 (P < 0.005). There was no difference among the four regions in frequency of "adding salt on the table." The region of the United States that includes the "stroke belt" has dietary patterns that may contribute to the high prevalence of hypertension and cardiovascular disease.


Haag, M. (2003). "Essential fatty acids and the brain." Can J Psychiatry 48(3): 195-203.

            OBJECTIVE: To review the role of essential fatty acids in brain membrane function and in the genesis of psychiatric disease. METHOD: Medline databases were searched for published articles with links among the following key words: essential fatty acids, omega-3 fatty acids, docosahexanoic acid, eicosapentanoic acid, arachidonic acid, neurotransmission, phospholipase A2, depression, schizophrenia, mental performance, attention-deficit hyperactivity disorder, and Alzheimer's disease. Biochemistry textbooks were consulted on the role of fatty acids in membrane function, neurotransmission, and eicosanoid formation. The 3-dimensional structures of fatty acids were obtained from the Web site of the Biochemistry Department, University of Arizona (2001). RESULTS: The fatty acid composition of neuronal cell membrane phospholipids reflects their intake in the diet. The degree of a fatty acid's desaturation determines its 3-dimensional structure and, thus, membrane fluidity and function. The ratio between omega-3 and omega-6 polyunsaturated fatty acids (PUFAs), in particular, influences various aspects of serotoninergic and catecholaminergic neurotransmission, as shown by studies in animal models. Phospholipase A2 (PLA2) hydrolyzes fatty acids from membrane phospholipids: liberated omega-6 PUFAs are metabolized to prostaglandins with a higher inflammatory potential, compared with those generated from the omega-3 family. Thus the activity of PLA2 coupled with membrane fatty acid composition may play a central role in the development of neuronal dysfunction. Intervention trials in human subjects show that omega-3 fatty acids have possible positive effects in the treatment of various psychiatric disorders, but more data are needed to make conclusive directives in this regard. CONCLUSION: The ratio of membrane omega-3 to omega-6 PUFAs can be modulated by dietary intake. This ratio influences neurotransmission and prostaglandin formation, processes that are vital in the maintenance of normal brain function.


Haag, M., O. N. Magada, et al. (2003). "Omega-3 fatty acids modulate ATPases involved in duodenal Ca absorption." Prostaglandins Leukot Essent Fatty Acids 68(6): 423-9.

            Dietary supplementation with fish oil that contains omega-3 polyunsaturated fatty acids has been shown to enhance bone density as well as duodenal calcium uptake in rats. The latter process is supported by membrane ATPases. The present in vitro study was undertaken to test the effect of omega-3 fatty acids on ATPase activity in isolated basolateral membranes from rat duodenal enterocytes. Ca-ATPase in calmodulin-stripped membranes was activated in a biphasic manner by docosahexanoic acid (DHA) (10-30 microg/ml) but not by eicosapentanoic acid (EPA). This effect was blocked partially by 0.5 microM calphostin (a protein kinase C blocker). DHA inhibited Na,K-ATPase (-49% of basal activity, [DHA]=30 microg/ml, P <0.01). This effect could be reversed partially by 50 microM genistein, a tyrosine kinase blocker. EPA also inhibited Na,K-ATPase: (-47% of basal activity, [EPA]=30 microg/ml, P <0.01), this effect was partially reversed by 100 microM indomethacin, a cyclo-oxygenase blocker. Omega-3 fatty acids are thus involved in multiple signalling effects that effect ATPases in BLM.


Guajardo, M. H., A. M. Terrasa, et al. (2003). "Protective effect of indoleamines on in vitro ascorbate-Fe2+ dependent lipid peroxidation of rod outer segment membranes of bovine retina." J Pineal Res 35(4): 276-82.

            Rod outer segment membranes (ROS) are highly vulnerable to autooxidation because of their high content of long chain polyunsaturated fatty acids (PUFAs). Melatonin and N-acetylserotonin are indoleamines synthesized in the pineal gland, retina and other tissues. These compounds are free radical scavengers and indirect antioxidants because of their stimulatory effect on antioxidative enzymes. We compared the in vitro protective effect of melatonin and N-acetylserotonin on the ascorbate-Fe2+ induced lipid peroxidation of PUFAs located in ROS membranes. This process was measured by chemiluminescence and fatty acid composition of total lipids of ROS. We assayed increasing concentrations of melatonin (0-10 mm) and N-acetylserotonin (0-2 mm). In both cases the total cpm originated from light emission (chemiluminescence) was found to be lower in those membranes incubated in the presence of either melatonin or N-acetylserotonin; this decreased proportional to the concentration of the indole. Thus, 10 mm melatonin and 2 mm N-acetylserotonin produced a reduction of 51 +/- 6 and 100% in the total chemiluminescene (lipid peroxidation), respectively. We also noticed a PUFAs protection: the docosahexaenoic acid content decreased considerably when the membranes were submitted to oxidative damage. This reduction was from 37.6 +/- 2.1% in the native membranes to 6.2 +/- 0.8% in those which were peroxidized. These changes were less pronounced in treated ROS membranes; as an example in the presence of 10 mm melatonin or 2 mm N-acetylserotonin we observed a content preservation of 22:6 n-3 (23.6 +/- 1.2 and 39.1 +/- 1.2% respectively). The concentration of each compound required to inhibit 50% of the lipid peroxidation (IC50) was 9.82 mm for melatonin and 0.43 mm for N-acetylserotonin, respectively. N-acetylserotonin shows a protective effect about 20 times higher than that of melatonin.


Gu, X., S. G. Meer, et al. (2003). "Carboxyethylpyrrole protein adducts and autoantibodies, biomarkers for age-related macular degeneration." J Biol Chem 278(43): 42027-35.

            Age-related macular degeneration (AMD) is a slow, progressive disease with both genetic and environmental risk factors. Free radical-induced oxidation of docosahexaenoate (DHA)-containing lipids generates omega-(2-carboxyethyl)pyrrole (CEP) protein adducts that are more abundant in ocular tissues from AMD than normal human donors. To understand better the role of oxidative damage in AMD, we have synthesized CEP-modified proteins, produced anti-CEP antibodies, and initiated analysis of CEP immunoreactivity and autoantibodies in human plasma. A highly selective rabbit polyclonal anti-CEP antibody was raised that binds CEP 1000 times more strongly than carboxypropylpyrrole, a close structural analogue. The CEP adduct uniquely indicates oxidative modification from DHA derivatives because CEP protein modifications cannot arise from any other common polyunsaturated fatty acid. Immunocytochemistry localized CEP to photoreceptor rod outer segments and retinal pigment epithelium in mouse retina and demonstrated more intense CEP immunoreactivity in photoreceptors from a human AMD donor compared with healthy human retina. The mean level of anti-CEP immunoreactivity in AMD human plasma (n = 19 donors) was 1.5-fold higher (p = 0.004) than in age-matched controls (n = 19 donors). Sera from AMD patients demonstrated mean titers of anti-CEP autoantibody 2.3-fold higher than controls (p = 0.02). Of individuals (n = 13) exhibiting both antigen and autoantibody levels above the mean for non-AMD controls, 92% had AMD. These results suggest that together CEP immunoreactivity and autoantibody titer may have diagnostic utility in predicting AMD susceptibility.


Gryglewicz, S., W. Piechocki, et al. (2003). "Preparation of polyol esters based on vegetable and animal fats." Bioresour Technol 87(1): 35-9.

            The possibility of using some natural fats: rapeseed oil, olive oil and lard, as starting material for the preparation of neopentyl glycol (NPG) and trimethylol propane (TMP) esters is reported. The syntheses of final products were performed by alcoholysis of fatty acid methyl esters, obtained from natural fats studied, with the appropriate polyhydric alcohol using calcium methoxide as a catalyst. The basic physicochemical properties of the NPG and TMP esters synthesized were the following: viscosity at 40 degrees C in the range of 13.5-37.6 cSt, pour point between -10.5 and -17.5 degrees C and very high viscosity indices, higher than 200. Generally, the esters of neopentyl alcohols were characterized by higher stability in thermo-oxidative conditions in comparison to native triglycerides. Due to the low content of polyunsaturated acids, the olive oil based esters showed the highest thermo-oxidative resistance. Also, methyl esters of fatty acids of lard would constitute a good raw material for the synthesis of lubricating oils, provided that their saturated acids content was lowered. This permits synthesis of NPG and TMP esters with a lower pour point (below -10 degrees C) than natural lard (+33 degrees C).


Grundt, H., O. Hetland, et al. (2003). "Changes in tissue factor and activated factor XII following an acute myocardial infarction were uninfluenced by high doses of n-3 polyunsaturated fatty acids." Thromb Haemost 89(4): 752-9.

            Few data exist on the effects of n-3 polyunsaturated fatty acids (PUFAs) on the initiators and endstage products of coagulation following an acute myocardial infarction (MI). We assessed the long-term effects of n-3 PUFAs on postinfarct variations of tissue factor (TF), activated factor XII (FXIIa) and fibrin monomer (FM), and expected additional statin treatment to modify thrombogenicity. Acute MI patients (n = 300) were randomly allocated to a high dose of n-3 PUFAs or corn oil for at least one year. Plasma concentrations of TF, FXIIa and FM were unaffected by n-3 PUFAs as compared to corn oil, and were uninfluenced by additional statin treatment in subgroup analyses. TF decreased (p = 0.0001), while FXIIa increased during the first 6 weeks (p = 0.001). FM remained essentially unchanged during the entire observation period. In conclusion, TF, FXIIa and FM were unaffected by long-term treatment with high- dosed n-3 PUFAs and by additional statin treatment.


Grundt, H., D. W. Nilsen, et al. (2003). "Reduction in homocysteine by n-3 polyunsaturated fatty acids after 1 year in a randomised double-blind study following an acute myocardial infarction: no effect on endothelial adhesion properties." Pathophysiol Haemost Thromb 33(2): 88-95.

            We hypothesized that n-3 polyunsaturated fatty acids (n-3 PUFAs) as compared to corn oil administered for 1 year following an acute myocardial infarction (MI) may reduce plasma total homocysteine (p-tHcy), ultrasensitive C-reactive protein (microCRP), and the adhesive properties of the endothelium, expressed as soluble E-selectin (sE-selectin) and soluble intercellular adhesion molecule-1 (sICAM-1). In a prospective, randomised, double-blind study, 300 acute MI patients were allocated to highly concentrated n-3 PUFAs (n = 150) or corn oil (n = 150). After 1 year on treatment there was an intergroup difference in p-tHcy in favour of the n-3 group (n = 118), p = 0.022. However, sE-selectin, sICAM-1 and microCRP were unaffected by the treatment. In conclusion, reduction of p-tHcy by long-term n-3 PUFAs treatment was not associated with demonstrable effects on markers of endothelial adhesion properties.


Groscolas, R., F. Frechard, et al. (2003). "Metabolic fate of yolk fatty acids in the developing king penguin embryo." Am J Physiol Regul Integr Comp Physiol 285(4): R850-61.

            This study examines the metabolic fate of total and individual yolk fatty acids (FA) during the embryonic development of the king penguin, a seabird characterized by prolonged incubation (53 days) and hatching (3 days) periods, and a high n-3/n-6 polyunsaturated FA ratio in the egg. Of the approximately 15 g of total FA initially present in the egg lipid, 87% was transferred to the embryo by the time of hatching, the remaining 13% being present in the internalized yolk sac of the chick. During the whole incubation, 83% of the transferred FA was oxidized for energy, with only 17% incorporated into embryo lipids. Prehatching (days 0-49), the fat stores (triacylglycerol) accounted for 58% of the total FA incorporated into embryo lipid. During hatching (days 49-53), 40% of the FA of the fat stores was mobilized, the mobilization of individual FA being nonselective. At hatch, 53% of the arachidonic acid (20:4n-6) of the initial yolk had been incorporated into embryo lipid compared with only 15% of the total FA and 17-24% of the various n-3 polyunsaturated FA. Similarly, only 32% of the yolk's initial content of 20:4n-6 was oxidized for energy during development compared with 72% of the total FA and 58-66% of the n-3 polyunsaturated FA. The high partitioning of yolk FA toward oxidization and the intense mobilization of fat store FA during hatching most likely reflect the high energy cost of the long incubation and hatching periods of the king penguin. The preferential partitioning of 20:4n-6 into the structural lipid of the embryo in the face of its low content in the yolk may reflect the important roles of this FA in tissue function.


Griffin, J. L., K. K. Lehtimaki, et al. (2003). "Assignment of 1H nuclear magnetic resonance visible polyunsaturated fatty acids in BT4C gliomas undergoing ganciclovir-thymidine kinase gene therapy-induced programmed cell death." Cancer Res 63(12): 3195-201.

            Polyunsaturated fatty acids (PUFAs), as detected by (1)H nuclear magnetic resonance (NMR) spectroscopy, accumulate into BT4C glioma during ganciclovir-thymidine kinase gene therapy-induced programmed cell death (PCD). In this study, we have quantified the (1)H NMR visible lipids in vivo and characterized their biophysical and biochemical nature in these tumors during PCD both ex vivo and in vitro. Concentrations of (1)H NMR-detectable PUFAs increased 3-fold with pattern recognition identifying CH = CH and CH = CHCH(2)CH = CH as the most significant in monitoring the dynamics of PCD. The increase in PUFAs was equivalent to 70% of that in CH(2)CH(2)CH(2)-saturated lipid peak at 1.3 ppm. Ex vivo tumor samples, obtained from in situ funnel frozen tumors, showed very similar macromolecular peaks, as studied using high-resolution magic angle spinning (1)H NMR at 14.1 T, to those detected in vivo at 4.7 T. Line widths of lipid peaks were not influenced by the spin rate within the range of 1-9 kHz or temperature between 277 and 293 K, showing high degree of (1)H NMR detection of these peaks in vivo. These biophysical results additionally corroborate the idea that cytoplasmic lipid vesicles are the source of (1)H NMR lipid signals. Two-dimensional (1)H NMR ex vivo and tumor lipid extracts in vitro showed that the PUFA signals are in the same chemical compounds and consist of largely 18:1 and 18:2 lipids. Furthermore, it is suggested that the (1)H NMR lipids detected during PCD arise from cell constituent breakdown products forming lipid vesicles into dying cells.


Granlund, L., L. K. Juvet, et al. (2003). "Trans10, cis12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARgamma modulator." J Lipid Res 44(8): 1441-52.

            A group of polyunsaturated fatty acids called conjugated linoleic acids (CLAs) are found in ruminant products, where the most common isomers are cis9, trans11 (c 9,t11) and trans10, cis12 (t10,c12) CLA. A crude mixture of these isomers has been shown in animal studies to alter body composition by a reduction in body fat mass as well as an increase in lean body mass, with the t10,c12 isomer having the most pronounced effect. The objective of this study was to establish the molecular mechanisms by which t10,c12 CLA affects lipid accumulation in adipocytes. We have shown that t10,c12 CLA prevents lipid accumulation in human and mouse adipocytes at concentrations as low as 5 microM and 25 microM, respectively. t10,c12 CLA fails to activate peroxisome proliferator-activated receptor gamma (PPARgamma) but selectively inhibits thiazolidinedione-induced PPARgamma activation in 3T3-L1 adipocytes. Treatment of mature adipocytes with t10,c12 CLA alone or in combination with Darglitazone down-regulates the mRNA expression of PPARgamma as well as its target genes, fatty acid binding protein (aP2) and liver X receptor alpha (LXRalpha). Taken together, our results suggest that the trans10, cis12 CLA isomer prevents lipid accumulation in adipocytes by acting as a PPARgamma modulator.


Grandjean, P. and P. Weihe (2003). "Arachidonic acid status during pregnancy is associated with polychlorinated biphenyl exposure." Am J Clin Nutr 77(3): 715-9.

            BACKGROUND: Seafood is an important source of long-chain polyunsaturated fatty acids (LCPs), which are essential for normal growth and development. However, the nutritional benefits could be limited by polychlorinated biphenyl (PCB) contamination. In particular, inhibition of desaturase activities by PCBs may affect the maintenance of arachidonic acid (AA) status during development. OBJECTIVE: The aim was to evaluate AA status in a birth cohort from a fishing community with a high seafood intake and a wide range of PCB exposures. DESIGN: We measured LCP concentrations in paired mother and umbilical cord serum samples obtained from 182 consecutive births in the Faroe Islands, where PCB-contaminated whale blubber forms part of the diet. PCB exposure was determined from maternal concentrations. RESULTS: Serum phospholipid AA concentrations averaged 9.14% and 16.5% (by wt) in maternal and cord serum, respectively. After adjustment for gestational age and concentrations of linoleic, alpha-linolenic, and eicosapentaenoic acids, a decrease in AA concentrations of 0.17% (by wt) (95% CI: 0.03%, 0.31%) and 0.31% (by wt) (95% CI: 0.10%, 0.52%) was seen in maternal and cord serum, respectively, for each doubling of PCB exposure. CONCLUSIONS: Increased PCB exposure was associated with a modest decrease in serum AA concentrations, which is in accordance with the experimental evidence of desaturase inhibition by PCBs. Such interference with LCP utilization could attenuate the beneficial effects of the essential lipids contained in seafood. Because AA is of key importance for growth and development, these results suggest that this possible mechanism for PCB toxicity deserves to be explored.


Goodstine, S. L., T. Zheng, et al. (2003). "Dietary (n-3)/(n-6) fatty acid ratio: possible relationship to premenopausal but not postmenopausal breast cancer risk in U.S. women." J Nutr 133(5): 1409-14.

            Recent research has suggested that an increased (n-3) fatty acid intake and/or increased (n-3)/(n-6) polyunsaturated fatty acid (PUFA) ratio in the diet is associated with a lower breast cancer risk. This case-control study investigated the association between intake of (n-3) and other fatty acids and the (n-3)/(n-6) PUFA ratio and breast cancer risk. After combining data from two related case-control studies in Connecticut, we had information available on a total of 1119 women (565 cases and 554 controls). Cases were all histologically confirmed, incident breast carcinoma patients. Controls were hospital-based (Yale-New Haven Hospital study site) and population-based (Tolland County study site). Information on dietary intake was obtained through a validated food-frequency questionnaire. Standard multivariate methods were used to address the independent effects of specific fatty acids, fat classes and macronutrients on breast cancer risk. In the full study population, there were no significant trends for any macronutrient/fatty acid when comparing the highest to the lowest quartile of intake. When the analysis was restricted to premenopausal women, consumption of the highest compared with the lowest quartile of the (n-3)/(n-6) PUFA ratio was associated with a nonsignificant 41% lower risk of breast cancer [odds ratio (OR) = 0.59, 95% confidence interval (CI) 0.29, 1.19, P for trend = 0.09]. A higher (n-3)/(n-6) PUFA ratio was significantly associated with a lower risk of breast cancer when the data were restricted to the Tolland County (population-based) study site; OR = 0.50, 95% CI 0.27, 0.95, P for trend = 0.02. These results are consistent with the hypothesis that a higher (n-3)/(n-6) PUFA ratio may reduce the risk of breast cancer, especially in premenopausal women.


Gomez Garcia, V., M. R. Sanz Sampelayo, et al. (2003). "Polyunsaturated fatty acids and parasitism: effect of a diet supplemented with fish oil on the course of rat trichinellosis." Vet Parasitol 117(1-2): 85-97.

            Dietary fish oil has a beneficial effect on heart and some bacterial diseases and apart from other effects, some studies have revealed their ability to modulate the course of inflammatory and autoimmune diseases. The study here reported was designed to evaluate the possible influence of a fish oil supplement on the course of a Trichinella infection. Nutritional, parasitological and immunological parameters were analyzed. Two groups of 20 Wistar rats, one fed a standard diet and the other one a standard diet supplemented with fish oil, were infected with 1000 L1 larvae. Other two uninfected groups served as control. Results were as follows: fish oil diet intake and infection have, respectively, a positive and a negative effect on growth and food utilization. The negative effect is detected later in animals fed the fish oil diet. A reduction of 30.9 and 36.6% in the number of adult worms and L1 larvae, respectively, was observed in the fish oil group as compared to the standard diet group. Production of IFNgamma (Th1 response) and IL4 (Th2) response was measured in stimulated splenic cells. The fish oil diet increased both IFNgamma and IL4 levels. At 6 days after infection both IFNgamma and IL4 responses were detected, but at 36 days after infection only IL4 was detected in the standard group. The level of somatic and cuticular antibodies was not affected by the diet.


Gogolewski, M., M. Nogala-Kalucka, et al. (2003). "Studies on dimerisation of tocopherols under the influence of methyl linoleate peroxides." Nahrung 47(2): 74-8.

            The stability of plant oils is related to the level of polyunsaturated fatty acids and the presence of native antioxidants--especially tocopherols. During storage, lipids or the fat products undergo oxidation and tocopherol dimers and trimers are formed. These compounds possess reducing and antioxidant properties and participate in oxidation clearly inhibiting this process. In the present study, the correlation between levels of peroxides formed during autoxidation of methyl linoleate and simultaneous decomposition of tocopherols was examined. The peroxide value was investigated. Quantities of decomposed tocopherols and formation of their dimers were determined by high-performance liquid chromatography (HPLC). Mass spectrum analysis confirmed thatthe analysed compounds were dimes. Dimerisation of gamma-T begins at the smaller quantity of the methyl linoleate peroxides than dimerisation of delta-T. At the beginning of methyl linoleate autoxidation dimerisation of gamma-T in relation to its loss was smaller. The quantity of gamma-T dimers with ether bonds in total dimers pointed to faster binding of phenoxy radicals than transformation into the phenyl ones. delta-T dimers with phenyl bonds constitute about 65% of the total. The quantity of peroxides in methyl linoleate, necessary for quantitative and qualitative changes of homologous tocopherols, decreased from delta-T to alpha-T.


Gobel, Y., B. Koletzko, et al. (2003). "Parenteral fat emulsions based on olive and soybean oils: a randomized clinical trial in preterm infants." J Pediatr Gastroenterol Nutr 37(2): 161-7.

            OBJECTIVE: To evaluate in premature infants a new parenteral lipid emulsion based on olive and soybean oils (ratio 4:1), with less polyunsaturated fatty acids (PUFA) and more alpha-tocopherol than standard soybean oil emulsion. STUDY DESIGN: Premature infants (gestational age, 28-<37 weeks) were randomized to receive one of the two emulsions within the first 72 hours of life. The triglyceride dose was increased to 2 g/kg/day within 3 days. Plasma phospholipid fatty acids, alpha-tocopherol/lipid ratio, and urinary malondialdehyde (MDA) excretion were determined at baseline and after 7 days. RESULTS: Of 45 recruited infants, 33 completed the study per protocol (15 soybean oil, 18 olive oil emulsion). At study end, groups did not differ in plasma phospholipid arachidonic acid, total n-6 and n-3 metabolites, but the olive oil group showed higher values of the PUFA intermediates C18:3n-6 (0.19% +/- 0.01% vs. 0.13% +/- 0.02%, P < 0.05) and C20:3n-6 (2.92% +/- 0.12% vs. 2.21% +/- 0.17%, P = 0.005). The plasma alpha-tocopherol/total lipd ratio was higher in the olive oil group (2.45 +/- 0.27 micromol/mmol vs. 1.90 +/- 0.08 micromol/mmol, P = 0.001), whereas urinary MDA excretion did not differ. CONCLUSION: The lower PUFA supply with the olive/soybean oil emulsion appears to enhance linoleic acid conversion. The reduced PUFA content, combined with a higher antioxidant intake in the olive oil group, results in an improved vitamin E status. The olive oil-based emulsion is a valuable alternative for parenteral feeding of preterm infants who are often exposed to oxidative stress, while their antioxidative defense is weak.


Glew, R. H., J. Casados, et al. (2003). "Correlation of the fatty acid composition and fluid property of the cholesteryl esters in the serum of Nigerian children with sickle cell disease and healthy controls." Prostaglandins Leukot Essent Fatty Acids 68(1): 61-8.

            In a previous study conducted in Nigeria, we found that children with sickle cell disease (SCD) had exceedingly low total serum cholesterol levels (mean=100-102mg/dl). The fact that significant reductions in the levels of certain polyunsaturated fatty acids (PUFA) have been documented in the serum phospholipids of these same SCD subjects led us to inquire as to the fatty acid composition of the cholesteryl esters (CE) in their serum. Lecithin:cholesterol acyl transferase (LCAT), the enzyme in blood that catalyzes the reaction in which tissue cholesterol is acylated prior to its removal from cell membranes, is relatively specific for certain PUFA. CE in blood serum from 43 male and 42 female children with SCD, ages 4-18 years, and equal numbers of age- and gender-matched controls were analyzed for their fatty acid composition. Relative to the non-SCD controls, the CE of the SCD subjects contained 9% less linoleic acid, 16% less arachidonic acid, 40% less alpha-linolenic acid, 50% less eicosapentaenoic acid, and 36% less docosahexaenoic acid, but 15% more palmitic acid and 10% more oleic acid. Overall, the acyl chains of the CE of the SCD subjects were less fluid than those of the controls, as determined by comparison of their mean melting points (MMP) and double bond indices (DBI). MMP and DBI were both estimated from the individual constituent fatty acids comprising the CE acyl chains. The strongest correlations between MMP and fatty acid mole percent were seen with palmitic acid and linoleic acid. These results show that the fatty acid composition of the serum CE of children with SCD is abnormal relative to controls who do not have this hematologic disorder. We speculate that suboptimal fatty acid nutrition in Nigerian children with SCD compromises their ability to remove cholesterol from their tissues due to preference of the LCAT enzyme for PUFA, thereby accounting, in part at least, for the low total serum cholesterol levels one finds in children with SCD.


Giudetti, A. M., S. Sabetta, et al. (2003). "Differential effects of coconut oil- and fish oil-enriched diets on tricarboxylate carrier in rat liver mitochondria." J Lipid Res 44(11): 2135-41.

            The mitochondrial tricarboxylate carrier (TCC) plays an important role in lipogenesis being TCC-responsible for the efflux from the mitochondria to the cytosol of acetyl-CoA, the primer for fatty acid synthesis. In this study, we investigated the effects of two high-fat diets with different fatty acid composition on the hepatic TCC activity. Rats were fed for 3 weeks on a basal diet supplemented with 15% of either coconut oil (CO), abundant in medium-chain saturated fatty acids, or fish oil (FO), rich in n-3 polyunsaturated fatty acids. Mitochondrial fatty acid composition was differently influenced by the dietary treatments, while no appreciable change in phospholipid composition and cholesterol level was observed. Compared with CO, the TCC activity was markedly decreased in liver mitochondria from FO-fed rats; kinetic analysis of the carrier revealed a decrease of the Vmax, with no change of the Km. No difference in the Arrhenius plot between the two groups was observed. Interestingly, the carrier protein level and the corresponding mRNA abundance decreased following FO treatment. These data indicate that FO administration markedly decreased the TCC activity as compared with CO. This effect is most likely due to a reduced gene expression of the carrier protein.


Gil, A., M. Ramirez, et al. (2003). "Role of long-chain polyunsaturated fatty acids in infant nutrition." Eur J Clin Nutr 57 Suppl 1: S31-4.

            OBJECTIVE: To review briefly the influence of dietary long-chain polyunsaturated fatty acids (LC-PUFA) on tissue composition and functionality in early infancy. Moreover, the influences of LC-PUFA sources on plasma composition as well as the effects of these fatty acids on intestinal repair after malnutrition are discussed. RESULTS: Human milk not only supplies essential fatty acids but also contains up to 2% of the total fatty acids as LC-PUFA, of which arachidonic acid (AA) and docosahexaenoic acid (DHA) are considered the most important. Plasma and erythrocyte levels of both AA and DHA are decreased in infants fed artificial standard milk formulae. However, the supplementation of formulae with these fatty acids in amounts close to that of human milk leads to tissue LC-PUFA patterns similar to those of breast-fed infants. However, the bioavailability of LC-PUFA depends on the typical LC-PUFA source; egg phospholipids increases both AA and DHA in plasma phospholipids and HDL more than a mixture of tuna and fungal triglycerides. CONCLUSIONS: Dietary LC-PUFA affects positively the growth and development of the infant and ameliorates the visual and cognitive functions, particularly in preterm infants. Likewise, LC-PUFA improves intestinal repair in severe protein-energy malnutrition; therefore, its qualitative and quantitative dietary supply should be considered.


Giamarellos-Bourboulis, E. J., S. Skiathitis, et al. (2003). "Lipid peroxidation by Pseudomonas aeruginosa in the pathogenesis of nosocomial sepsis." J Postgrad Med 49(1): 11-6; discussion 16.

            BACKGROUND: To study whether Pseudomonas aeruginosa may directly trigger peroxidation of polyunsaturated fatty acids, since lipid peroxidation is a mechanism involved in the pathogenesis of sepsis. METHODS: Gamma-linolenic acid (GLA) was administered intravenously at a dose of 25mg/kg in an infusion time of 10 minutes to seven male rabbits. Blood samples were collected from the hepatic veins and from the carotid artery at regular time intervals. One clinical isolate was ex vivo incubated with the serum derived from the latter samples and concentrations of malondialdehyde (MDA) were determined during incubation in the growth medium by the thiobarbiturate assay. RESULTS: Elevated concentrations of MDA compared to their basal levels were found over the first three hours of incubation in the presence of samples collected 30 to 60 minutes after the end of the infusion of GLA. After infusion of GLA concentrations of arachidonic acid in the serum increased to concentrations comparable to those detected in sepsis. CONCLUSION: Direct triggering of lipid peroxidation by nosocomial isolates might be proposed as a pathogenetic mechanism of sepsis.


Germain, E., P. Bonnet, et al. (2003). "Anthracycline-induced cardiac toxicity is not increased by dietary omega-3 fatty acids." Pharmacol Res 47(2): 111-7.

            Exogenous n-3 polyunsaturated fatty acids (PUFA) and specially docosahexaenoic acid (DHA) have been previously reported to potentiate the efficacy of anticancer agents that generate an oxidative stress, such as anthracyclines, by enhancing the susceptibility of cell membranes to lipid peroxidation. Since lipid peroxidation has also been suggested to mediate anthracycline-induced heart failure, we designed a study aimed at investigating whether a DHA-enriched diet coupled with controlled oxidative conditions prevents or aggravates this serious side effect in vivo.Female Sprague-Dawley rats were submitted for at least 3 weeks to diet enriched in DHA, which was provided either as natural oil (sardine oil, experiment 1) or in a purified form (DHASCO, experiment 2). At the same time, to constrain the nutritional oxidative status, the anti-oxidant Vitamin E or the pro-oxidant menadione/sodium ascorbate redox mixture was added. Then, epirubicin was administered weekly at two cumulative doses, 9 mg x kg(-1) (experiment 1) or 15 mg x kg(-1) (experiment 2). Cardiotoxicity was assessed by electrocardiographic (ECG) and hemodynamic measurements, completed with histological examination. Epirubicin-induced dose-dependent mortality, alterations of hemodynamic parameters and histological damages, all features characterizing the occurrence of congestive heart failure. Moreover, the addition of anti- or pro-oxidant did not change the hemodynamics either at the lowest (experiment 1) or the highest dose (experiment 2). Similarly, the ECG measurements and histological examinations did not reveal any difference. DHA was actually incorporated, as evaluated through the adipose tissue fatty acid composition. All these observations indicated that the DHA-enriched diet, placed under controlled oxidative conditions, did not appear to prevent but neither to aggravate epirubicin-induced cardiotoxicity. These findings support the idea that DHA improves the anthracycline therapeutic index.


Gentile, G., V. Bonasera, et al. (2003). "Shewanella sp. GA-22, a psychrophilic hydrocarbonoclastic antarctic bacterium producing polyunsaturated fatty acids." J Appl Microbiol 95(5): 1124-33.

            AIMS: The effects of different growth media and temperature on production of polyunsaturated fatty acids (PUFA) by Shewanella sp. GA-22 were investigated. The attempts to characterize the GA-22 genes, homologous to those of PUFA biosynthesis gene cluster, was performed. METHODS AND RESULTS: Physiological and phylogenetic characterization of new Antarctic isolate GA-22 was performed. Total fatty acids were isolated from the cells growing under different conditions and analysed by gas chromatography-mass spectrometry (GC-MS). Using degenerated primers derived from the conserved regions within PUFA fatty acid synthase operons, five fragments of homological genes were amplified from GA-22 DNA, and two of them corresponding to pfaA and pfaC synthase subunits were sequenced. CONCLUSIONS: Strain GA-22 was shown to be able to produce three different PUFA: linoleic, arachidonic and eicosapentaenoic acids. The PUFA production was temperature- and carbon source-dependent. The deduced gene products exhibited high similarity to corresponding fatty acid synthases PfaA and PfaC. SIGNIFICANCE AND IMPACT OF STUDY: The PUFA production was detected on media supplemented with crude oil, gasoline and n-tetradecane. The apparent conservation of PUFA genes may point to the potential utilization of designed primers as functional markers in culture-independent ecological studies, and for initial screening in biotechnological fields.


Ge, L., J. S. Gordon, et al. (2003). "Identification of the delta-6 desaturase of human sebaceous glands: expression and enzyme activity." J Invest Dermatol 120(5): 707-14.

            Delta-6 desaturase, also known as fatty acid desaturase-2 (FADS2), is a component of a lipid metabolic pathway that converts the essential fatty acids linoleate and alpha-linolenate into long-chain polyunsaturated fatty acids. Isolation of Delta-6 desaturase/FADS2 cDNA from human skin predicts an identical protein to that expressed in human brain and Southern analysis indicates a single locus, together suggestive of a single Delta-6 desaturase/FADS2 gene. Within human skin, Delta-6 desaturase/FADS2 mRNA and protein expression is restricted to differentiating sebocytes located in the suprabasal layers of the sebaceous gland. Enzymatic analysis using CHO cells overexpressing human Delta-6 desaturase/FADS2 indicates catalysis of a "polyunsaturated fatty acid type" reaction, but also an unexpected "sebaceous-type" reaction, that of converting palmitate into the mono-unsaturated fatty acid sapienate, a 16-carbon fatty acid with a single cis double bond at the sixth carbon from the carboxyl end. Sapienate is the most abundant fatty acid in human sebum, and among hair-bearing animals is restricted to humans. This work identifies Delta-6 desaturase/FADS2 as the major fatty acid desaturase in human sebaceous glands and suggests that the environment of the sebaceous gland permits catalysis of the sebaceous-type reaction and restricts catalysis of the polyunsaturated fatty acid type reaction.


Gazzola, J., E. F. Martins, et al. (2003). "Cholesterol changes the fatty acid composition of rat enterocytes." Braz J Med Biol Res 36(1): 137-41.

            The effect of free cholesterol on the fatty acid composition and growth of rat fetal enterocytes was investigated in the absence and presence of 10% (v/v) fetal calf serum. Cholesterol caused a significant reduction of cell number after 6 and 12 h in culture. The fatty acid composition of enterocytes cultured in the presence of serum was also changed by the presence of 20 microM cholesterol. The fatty acid profile was determined by HPLC using fluorescence detection (325 nm excitation and 395 nm emission). Cholesterol (20 microM) increased the proportion (given in percentage of the total fatty acids) of the following fatty acids in cultured cells: lauric (by 42%), oleic (by 34%), linoleic (by 44%) and gamma-linolenic (by 20%) acids and reduced the proportion of palmitic (by 12%), stearic (by 20%), arachidonic (by 21%) and docosahexaenoic (by 44%) acids. In addition to modifying the content of individual fatty acids, cholesterol increased the polyunsaturated/saturated fatty acid ratio from 0.48 to 0.67 and the unsaturation index from 67.12 to 75.30. This is the first evidence that cholesterol modifies fatty acid composition possibly via de novo fatty acid synthesis and desaturation.


Gavazza, M. and A. Catala (2003). "Melatonin preserves arachidonic and docosapentaenoic acids during ascorbate-Fe2+ peroxidation of rat testis microsomes and mitochondria." Int J Biochem Cell Biol 35(3): 359-66.

            The pineal hormone melatonin (N-acetyl, 5-methoxytryptamine) was recently accepted to act as an antioxidant under both in vivo and in vitro conditions. In this study, we examined the possible preventive effect of melatonin on ascorbate-Fe(2+) lipid peroxidation of rat testis microsomes and mitochondria. Special attention was paid to the changes produced on the highly polyunsaturated fatty acids C20:4 n6 and C22:5 n6. The lipid peroxidation of testis microsomes or mitochondria produced a significant decrease of C20:4 n6 and C22:5 n6. The light emission (chemiluminescence) used as a marker of lipid peroxidation was similar in both kinds of organelles when the control and peroxidized groups were compared. Both long chain polyunsaturated fatty acids were protected when melatonin was incorporated either in microsomes or mitochondria. The melatonin concentration required to inhibit by 100% the lipid peroxidation process was 5.0 and 1.0mM in rat testis microsomes and mitochondria, respectively. IC 50 values calculated from the inhibition curve of melatonin on the chemiluminescence rates were higher in microsomes (4.98 mM) than in mitochondria (0.67 mM). The protective effect observed by melatonin in rat testis mitochondria was higher than that observed in microsomes which could be explained if we consider that the sum of C20:4 n6+C22:5 n6 in testis microsomes is two-fold greater than present in mitochondria.


Garg, T. K. and J. Y. Chang (2003). "Oxidative stress causes ERK phosphorylation and cell death in cultured retinal pigment epithelium: Prevention of cell death by AG126 and 15-deoxy-delta 12, 14-PGJ2." BMC Ophthalmol 3(1): 5.

            BACKGROUND: The retina, which is exposed to both sunlight and very high levels of oxygen, is exceptionally rich in polyunsaturated fatty acids, which makes it a favorable environment for the generation of reactive oxygen species. The cytotoxic effects of hydrogen peroxide (H2O2) induced oxidative stress on retinal pigment epithelium were characterized in this study. METHODS: The MTT cell viability assay, Texas-Red phalloidin staining, immunohistochemistry and Western blot analysis were used to assess the effects of oxidative stress on primary human retinal pigment epithelial cell cultures and the ARPE-19 cell line. RESULTS: The treatment of retinal pigment epithelial cells with H2O2 caused a dose-dependent decrease of cellular viability, which was preceded by a significant cytoskeletal rearrangement, activation of the Extracellular signal-Regulated Kinase, lipid peroxidation and nuclear condensation. This cell death was prevented partially by the prostaglandin derivative, 15d-PGJ2 and by the protein kinase inhibitor, AG126. CONCLUSION: 15d-PGJ2 and AG126 may be useful pharmacological tools in the future capable of preventing oxidative stress induced RPE cell death in human ocular diseases.


Garcia-Pelayo, M. C., E. Garcia-Peregrin, et al. (2003). "Modification of phospholipids fatty acid composition in reuber H35 hepatoma cells: effect on HMG-CoA reductase activity." J Cell Biochem 90(3): 586-91.

            There is controversy about the effect of saturated and polyunsaturated fats on 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, the main regulatory enzyme of cholesterogenic pathway. Results from dietary studies are difficult to interpret because diets normally contain a mixture of fatty acids. Therefore, we have used Reuber H35 hepatoma cells whose phospholipids were enriched in different individual fatty acids and have studied their effects on the cellular reductase activity. Lauric, myristic, eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids were supplemented to the culture medium coupled to bovine serum albumin. The four fatty acids were incorporated into phospholipids from cells grown in media containing whole serum or lipoprotein-poor serum (LPPS). Reductase activity of cells cultivated in a medium with LPPS was three to four times higher than those cultivated in medium with whole serum. Saturated fatty acids increased reductase activity of cells grown in medium with whole serum, whereas n-3 polyunsaturated fatty acids (PUFA) decreased it. However, both saturated and polyunsaturated fatty acids increased reductase activity when serum lipoproteins were removed. In conclusion, this is one of the first reports demonstrating that saturated and n-3 PUFA only show differential effects on HMG-CoA reductase activity in the presence of lipoproteins.


Gaiva, M. H., R. C. Couto, et al. (2003). "Diets rich in polyunsaturated fatty acids: effect on hepatic metabolism in rats." Nutrition 19(2): 144-9.

            OBJECTIVE: We investigated the effect of diets rich in omega-6 and omega-3 fatty acids on hepatic metabolism. METHODS: Male Wistar rats, just weaned, were fed ad libitum for 8 wk with one of the following diets: rat chow (C), rat chow containing 15% (w/w) soybean oil (S), rat chow containing 15% (w/w) fish oil (F), and rat chow containing 15% soy bean and fish oil (SF; 5:1, w/w). Casein was added to the fatty diets to achieve the same content of protein (20%) as the control chow. The rats were killed by decapitation, and the hepatic tissue was removed and weighed. Tissue lipid, glycogen, and protein content, in vivo lipogenesis rate, and adenosine triphosphate citrate lyase and malic enzyme activities were evaluated. Plasma total lipids, triacylglycerol, and cholesterol concentrations were assessed. RESULTS: Body weight gain was higher in F and SF than in C and S rats. Liver weight, lipid content, and lipogenesis rate increased in F and SF rats, although adenosine triphosphate citrate lyase activity decreased. Glycogen concentration decreased in S, F, and SF rats compared with C rats. Plasma total lipids and triacylglycerol concentrations were lower in F and SF than in C rats. Total and high-density lipoprotein cholesterol (HDL-C) plasma levels decreased in F rats, with maintenance of the total:HDL-C ratio. In SF rats, an increase in HDL-C led to a lower total:HDL-C ratio. CONCLUSIONS: These results indicated that an enrichment of the diet with omega-3 polyunsaturated fatty acids produces hypolipidemia but may cause changes in liver metabolism that favor lipid deposition. They also suggested that the addition of a small amount of eicosapentaenoic and docosahexaenoic polyunsaturated fatty acids to an omega-6-rich diet further improve the circulating lipid profile, in comparison with an omega-3-rich diet, but it does not prevent excess liver lipid accumulation.


Gago-Dominguez, M., J. M. Yuan, et al. (2003). "Opposing effects of dietary n-3 and n-6 fatty acids on mammary carcinogenesis: The Singapore Chinese Health Study." Br J Cancer 89(9): 1686-92.

            We investigated the effects of individual fatty acids on breast cancer in a prospective study of 35,298 Singapore Chinese women aged 45-74 years, who were enrolled during April 1993 to December 1998 (The Singapore Chinese Health Study). At recruitment, each study subject was administered, in-person, a validated, semiquantitative food frequency questionnaire consisting of 165 food and beverage items. As of December 31, 2000, 314 incident cases of breast cancer had occurred. We used the Cox regression methods to examine individual fatty acids in relation to breast cancer risk, with adjustment for age at baseline interview, year of interview, dialect group, level of education, daily alcohol drinking, number of live births, age when menstrual periods became regular, and family history of breast cancer. Consumption of saturated, monounsaturated or polyunsaturated fat overall was unrelated to risk. On the other hand, high levels of dietary n-3 fatty acids from fish/shellfish (marine n-3 fatty acids) were significantly associated with reduced risk. Relative to the lowest quartile of intake, individuals in the higher three quartiles exhibited a 26% reduction in risk (relative risk (RR)=0.74, 95% confidence interval (CI)=0.58, 0.94)); RRs were similar across the top three quartiles of intake (0.75, 0.75, 0.72, respectively). Overall, there was no association between n-6 fatty acids and breast cancer risk. However, among subjects who consumed low levels of marine n-3 fatty acids (lowest quartile of intake), a statistically significant increase in risk was observed in individuals belonging to the highest vs the lowest quartile of n-6 fatty acid consumption (RR=1.87, 95% CI=1.06-3.27); the corresponding RR for advanced breast cancer was 2.45 (95% CI=1.20-4.97, P for trend=0.01). To our knowledge, these are the first prospective findings linking the intake of marine n-3 fatty acids to breast cancer protection.


Fukushima, T., K. Tanaka, et al. (2003). "Changes in the fatty acid composition and hydroxyproline content in rat lung in relation to collagen synthesis after paraquat administration." Fukushima J Med Sci 49(1): 33-43.

            OBJECTIVES: Effect of paraquat on the fatty acid composition (weight percentage) of rat lung was studied with particular reference to the change of hydroxyproline content in the course of paraquat-induced dysfunction and subsequent repair. METHODS: Eight-week-old male Wistar rats were administered paraquat at 20 mg/kg body weight subcutaneously, and the wet weight, hydroxyproline content and fatty acid composition of lungs of each group rats were analyzed at 2, 7, 14 or 28 days after treatment, respectively. RESULTS: The percentage of palmitic acid (C16:0), arachidonic acid (C20:4) and docosahexaenoic acid (C22:6) significantly increased, and the percentage of oleic acid (C18:1) and the ratio of monounsaturated fatty acids/saturated fatty acids (M/S) significantly decreased comparing to control on day 28 after paraquat administration. The time-course of each fatty acid was observed for 28 days after paraquat administration. M/S ratio decreased after paraquat administration up to the 28th day, but the polyunsaturated fatty acids/saturated fatty acids (P/S) ratio decreased during the first 7 days, followed by a increase, and then reached higher level than the 0 day control at the 28th day. Hydroxyproline also increased between the 14th and the 28th days. Eicosapentaenoic acid (C20:5) had once increased during the first 2 days and decreased gradually, while C20:4 maintained high level in this period. C22:6 increased after paraquat administration and maintained high level up to the 28th day. This result indicated that desaturation and elongation in n-3 series fatty acids were accelerated after paraquat treatment, and consequently C20:5 was rapidly converted into C22:6 and decreased. CONCLUSIONS: Paraquat might cause elevation of unsaturated fatty acids, espe- cially C20:4 but not C20:5 by the stimulation of the fatty acid desaturase system, and could consequently stimulate local collagen synthesis by C20:4 metabolites in the healing stage.


Fujiwara, Y., M. Yokoyama, et al. (2003). "Analysis of the comprehensive effects of polyunsaturated fatty acid on mRNA expression using a gene chip." J Nutr Sci Vitaminol (Tokyo) 49(2): 125-32.

            To investigate the comprehensive effects of polyunsaturated fatty acids (PUFA) on gene expression, we analyzed changes of mRNA expression in PUFA-treated HepG2 cells using a DNA micro array. We incubated HepG2 cells for 24 h with or without 0.25 mM oleic acid (OA), arachidonic acid (AA), eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), and then compared the expression profiles of thousands of genes using a GeneChip. PUFA influenced the expression of various genes related to cell proliferation, growth and adhesion, as well as for many transcription factors including sterol regulatory element binding proteins (SREBP). Treatments with AA, EPA, and DHA repressed the expression of genes related to cholesterol and lipid metabolism. Moreover, data from gene chip analysis proved that PUPA reduced the expression ofprostasin, which is a serine protease. By measuring the mRNA levels of SREBPs, mevalonate pyrophosphatase and prostasin using quantitative RT-PCR, we confirmed the effect of PUFA revealed by gene chip analysis. These data might provide useful clues with which to explore novel functions of PUPA.


Fraser, D. D., S. Whiting, et al. (2003). "Elevated polyunsaturated fatty acids in blood serum obtained from children on the ketogenic diet." Neurology 60(6): 1026-9.

            The authors analyzed blood metabolites in nine children with epilepsy prior to starting the ketogenic diet (KD) and 3 to 4 weeks after KD therapy. Elevated beta-hydroxybutyrate and cortisol levels were observed in all children on the KD. Free fatty acids increased 2.2-fold on the KD, with significant elevations in most polyunsaturated fatty acids (PUFA; arachidonate increased 1.6- to 2.9-fold and docosahexaenoate increased 1.5- to 4.0-fold). The rise in total serum arachidonate correlated with improved seizure control. Elevated PUFA may represent a key anticonvulsant mechanism of the KD.


Fox, H., B. M. Ross, et al. (2003). "Degradation of specific polyunsaturated fatty acids in red blood cells stored at -20 degrees C proceeds faster in patients with schizophrenia when compared with healthy controls." Prostaglandins Leukot Essent Fatty Acids 69(5): 291-7.

            Deficits in red blood cell (RBC) polyunsaturated fatty acids (PUFAs) have been extensively reported in schizophrenia although reports are inconsistent. A possible explanation for this inconsistency is varying storage conditions of blood samples prior to analysis, especially freezer storage temperature. We conducted a prospective investigation of fatty acid degradation rates in RBCs from healthy control subjects when samples from each individual were stored at both -20 degrees C or -70 degrees C. Differences were detected between storage conditions. A second prospective study was conducted to investigate the effect of differential storage conditions on RBC membrane fatty acids from schizophrenic patients. We found that storage at -20 degrees C was associated with reduced levels of PUFAs. Comparison of decay rates suggest that schizophrenics decay approximately twice as rapidly as controls. Furthermore, this phenomenon appears to be specific for the longer chain PUFAs suggesting that an enzymatic process may be responsible, e.g. elevated phospholipase A(2) activity, as opposed to simple chemical oxidation.


Forsyth, J. S., P. Willatts, et al. (2003). "Long chain polyunsaturated fatty acid supplementation in infant formula and blood pressure in later childhood: follow up of a randomised controlled trial." Bmj 326(7396): 953.

            OBJECTIVE: To determine whether supplementation of infant formula milk with long chain polyunsaturated fatty acids (LCPUFAs) influences blood pressure in later childhood. DESIGN: Follow up of a multicentre, randomised controlled trial. SETTING: Four study centres in Europe. PARTICIPANTS: 147 formula fed children, with a reference group of 88 breastfed children. INTERVENTION: In the original trial newborn infants were randomised to be fed with a formula supplemented with LCPUFAs (n=111) or a formula without LCPUFAs but otherwise nutritionally similar (n=126). In the present follow up study the blood pressure of the children at age 6 years was measured. MAIN OUTCOME MEASURES: Systolic, diastolic, and mean blood pressure. RESULTS: 71 children in the LCPUFA supplementation group (64% of the original group) and 76 children in the non-supplementation group (60%) were enrolled into the follow up study. The LCPUFA group had significantly lower mean blood pressure (mean difference -3.0 mm Hg (95% confidence interval -5.4 mm Hg to -0.5 mm Hg)) and diastolic blood pressure (mean difference -3.6 mm Hg (-6.5 mm Hg to -0.6 mm Hg)) than the non-supplementation group. The diastolic pressure of the breastfed children (n=88 (63%)) was significantly lower than that of the non-supplemented formula group but did not differ from the LCPUFA formula group. CONCLUSIONS: Dietary supplementation with LCPUFAs during infancy is associated with lower blood pressure in later childhood. Blood pressure tends to track from childhood into adult life, so early exposure to dietary LCPUFAs may reduce cardiovascular risk in adulthood.


Formigoni, A. and E. Trevisi (2003). "Transition cow: interaction with fertility." Vet Res Commun 27 Suppl 1: 143-52.

            In recent years a progressive worsening of fertility indices in dairy cow herds has been observed. Several factors (genetic, dietary and management) seem to be more related to poor fertility than milk yield level. The degree and the length of the energy deficit during the transition period are inversely related to reproductive indices (e.g. conception rate is <30% for BCS decreases over one unit). A serious energy deficit reduces (or suppresses) pulsatile secretion of gonadotrophins (ovarian dysfunction and/or smaller follicles): IGF-I and insulin plasma levels (slower follicle growth and higher embryonic mortality); and progesterone production from the corpus luteum (higher rate of embryonic abortions). The diet influences fertility in several ways. Excess of rumen degradable proteins, apart from negative energy balance, negatively affects reproductive activity. Conversely, some nutrients (i.e. some polyunsaturated fatty acids or some amino acids) seem to show positive effects on fertility. Finally, the relationship between health status, often compromised during the transition period, and fertility efficiency is discussed. The release of cytokines seems to be related directly and indirectly (mainly by the change in usual hepatic metabolism to the malfunction of reproductive apparatus. Quick recovery of reproductive activity requires the adoption of strategies around calving to cover the higher environmental and nutritive requirements and to prevent disorders of any kind.


Forman, H. J., D. A. Dickinson, et al. (2003). "HNE--signaling pathways leading to its elimination." Mol Aspects Med 24(4-5): 189-94.

            The oxidation of polyunsaturated fatty acids results in the production of HNE, which can react through both non-enzymatic and enzyme catalyzed reactions to modify a number of cellular components, including proteins and DNA. Multiple pathways for its enzyme catalyzed elimination include oxidation of the aldehyde to a carboxylic acid, reduction of the aldehyde to an alcohol, and conjugation of the carbon-carbon double bond to glutathione (GSH). Interestingly, the enzymes that result in HNE elimination are induced by HNE itself although the chemical mechanism for signaling is not well understood. One of the striking effects of HNE is that after a transient decrease in GSH, synthesis of GSH is elevated through induction of glutamate cysteine ligase (GCL), which catalyzes the first step in de novo synthesis of GSH. GCL has two subunits, which are transcriptionally regulated by a wide variety of agents, including oxidants and electrophiles, such as HNE, which elevates both. The transcriptional regulation of GCL has been the subject of many investigations yielding a complex picture in which the pathways for up-regulation of the subunits appear to be independent and vary with inducing agent and cell type. We have found that in human bronchial epithelial cells, HNE acts through AP-1 activation with signaling through the JNK pathway, and that neither the ERK nor p38(MAPK) pathways is involved. With these results we review what is currently known about the signaling mechanisms for removal of HNE, focusing principally on conjugation mechanisms involving GSH.


Flint, A., B. Helt, et al. (2003). "Effects of different dietary fat types on postprandial appetite and energy expenditure." Obes Res 11(12): 1449-55.

            OBJECTIVE: Observational studies suggest that monounsaturated (MUFA) and trans fatty acids (TRANS) are more fattening than polyunsaturated fatty acids (PUFA). Therefore, the aim of this study was to investigate the acute effect of intake of PUFA, MUFA, or TRANS on appetite and energy expenditure (EE). RESEARCH METHODS AND PROCEDURES: Three test meals were randomly given in a cross-over design to 19 overweight (BMI: 26.8 +/- 0.4 kg/m2), young (25.2 +/- 0.7 years) men. The fat-rich breakfasts (0.8 g fat/kg body weight, 60% energy from fat) varied only in the source of C:18-fat. EE was measured continuously in a respiration chamber, and appetite sensations were rated by visual analog scales before and every 30 minutes, for 5 hours, after the meal. After 5 hours, an ad libitum meal was served, and energy intake was registered. Sensory evaluations of all meals were given using visual analog scales. Data were analyzed by two-way ANOVA. RESULTS: There were no differences in basal or postprandial values of appetite ratings and EE, in subsequent ad libitum energy intake, or in the sensory evaluation of the test meals among the 3 test days. DISCUSSION: Giving acutely large amounts of MUFA, PUFA, or TRANS did not impose any differences in appetite and EE in overweight humans. However, studies with extended protocols and other subject groups are warranted to investigate the long-term effect of dietary fat quality on the regulation of energy balance and body weight.


Finnegan, Y. E., A. M. Minihane, et al. (2003). "Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects." Am J Clin Nutr 77(4): 783-95.

            BACKGROUND: Dietary alpha-linolenic acid (ALA) can be converted to long-chain n-3 polyunsaturated fatty acids (PUFAs) in humans and may reproduce some of the beneficial effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cardiovascular disease risk factors. OBJECTIVE: This study aimed to compare the effects of increased dietary intakes of ALA and EPA+DHA on a range of atherogenic risk factors. DESIGN: This was a placebo-controlled, parallel study involving 150 moderately hyperlipidemic subjects randomly assigned to 1 of 5 interventions: 0.8 or 1.7 g EPA+DHA/d, 4.5 or 9.5 g ALA/d, or an n-6 PUFA control for 6 mo. Fatty acids were incorporated into 25 g of fat spread and 3 capsules to be consumed daily. RESULTS: The change in fasting or postprandial lipid, glucose, or insulin concentrations or in blood pressure was not significantly different after any of the n-3 PUFA interventions compared with the n-6 PUFA control. The mean (+/- SEM) change in fasting triacylglycerols after the 1.7-g/d EPA+DHA intervention (-7.7 +/- 4.99%) was significantly (P < 0.05) different from the change after the 9.5-g/d ALA intervention (10.9 +/- 4.5%). The ex vivo susceptibility of LDL to oxidation was higher after the 1.7-g/d EPA+DHA intervention than after the control and ALA interventions (P < 0.05). There was no significant change in plasma alpha-tocopherol concentrations or in whole plasma antioxidant status in any of the groups. CONCLUSION: At estimated biologically equivalent intakes, dietary ALA and EPA+DHA have different physiologic effects.


Finnegan, Y. E., D. Howarth, et al. (2003). "Plant and marine derived (n-3) polyunsaturated fatty acids do not affect blood coagulation and fibrinolytic factors in moderately hyperlipidemic humans." J Nutr 133(7): 2210-3.

            Dietary alpha-linolenic acid (ALA) can be converted to long-chain (n-3) PUFA in humans and may potentially reproduce the beneficial effects of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on risk factors for coronary heart disease (CHD). This study compared the effects of increased intakes of ALA with those of dietary EPA and DHA on blood coagulation and fibrinolytic factors in fasting subjects. A placebo-controlled, parallel study was conducted in 150 moderately hyperlipidemic subjects, age 25-72 y. Subjects were randomly assigned to one of five interventions and consumed a total intake of 0.8 or 1.7g/d EPA+DHA, 4.5 or 9.5g/d ALA or control (linoleic acid; LA) for 6 mo. Fatty acids were incorporated into 25 g of fat spread, which replaced the subject's normal spread and three capsules. Long-term supplementation with either dietary EPA+DHA or estimated biologically equivalent amounts of ALA did not affect factors VIIa, VIIc, VIIag, XIIa, XIIag, fibrinogen concentrations, plasminogen activator inhibitor-1 or tissue plasminogen activator activity compared with the control. (n-3) PUFA of plant or marine origin do not differ from one another or from LA in their effect on a range of blood coagulation and fibrinolytic factors.


Field, F. J., E. Born, et al. (2003). "Fatty acid flux suppresses fatty acid synthesis in hamster intestine independently of SREBP-1 expression." J Lipid Res 44(6): 1199-208.

            Hamsters were fed a control diet or diets containing palm, olive, safflower, or fish oil for 2 weeks. In villus cell populations from duodenum, jejunum, and ileum, rates of intestinal fatty acid and cholesterol synthesis were estimated, as were sterol regulatory element-binding protein (SREBP)-1a, SREBP-1c, SREBP-2, HMG-CoA synthase, fatty acid synthase, ATP citrate lyase, acetyl-CoA carboxylase mRNA levels, and SREBP-1 and SREBP-2 mass. Plasma cholesterol and triacylglcerol levels were increased in animals ingesting palm oil and decreased in animals ingesting fish oil. Fatty acid synthesis and fatty acid synthase activity were decreased in the proximal intestine of animals ingesting all the fat-containing diets. Intestinal cholesterol synthesis was unaltered. In animals fed fat, SREBP-1c gene expression was modestly increased in the duodenum of hamsters fed palm oil or olive oil, and decreased in animals ingesting safflower oil or fish oil. Fatty acid synthase, acetyl-CoA carboxylase, ATP citrate lyase, SREBP-2, and HMG-CoA synthase mRNA levels were not altered, nor were SREBP-1 or SREBP-2 mass. In the intestine, dietary polyunsaturated fatty acids suppress SREBP-1c mRNA without altering expression of its target genes, fatty acid synthase, acetyl-CoA carboxylase, or ATP citrate lyase. Fatty acid influx decreases intestinal fatty acid synthesis by a posttranscriptional mechanism independent of the SREBP pathway.


Ferrer, C., E. Pedragosa, et al. (2003). "Dietary lipids modify brush border membrane composition and nutrient transport in chicken small intestine." J Nutr 133(4): 1147-53.

            The influence of dietary fatty acids (FA) on intestinal brush border FA composition and nutrient transport functions was studied in broiler chickens. Ross chicks (2 wk old) were fed for 14 d a standard diet (CTL) or diets enriched with saturated fatty acids (SFA; 60 g/kg lard, LAR diet), (n-3) PUFA (60 g/kg linseed oil, LSO diet) and (n-6) PUFA (60 g/kg sunflower oil, SFO diet). The SFA of the brush border membrane were within 40-44% of total FA in spite of wide variability in dietary SFA concentration (13-32%); membrane (n-6) and (n-3) PUFA strongly reflected their dietary intake and thus the (n-6)/(n-3) ratio. However, the membrane polyunsaturated/saturated ratio (P/S) was close to unity, whereas in the diets, it was between 0.9 and 5. The transport kinetic constants (V(max), K(m), K(d)) of D-glucose (substrate of the sodium glucose cotransporter 1), L-lysine (through systems b(0,+) and y(+)(m)) and L-methionine (through systems B and L) were studied in jejunal brush border membrane vesicles. The changes in dietary FA intake did not affect the K(m) of the substrates for their transporters. Both LAR and SFO diets reduced the D-glucose V(max), which was compensated for by an increase in the K(d). The LAR diet reduced lysine transport across y(+)(m), whereas the LSO diet increased the V(max) for both lysine and methionine.


Fernandez de la Puebla, R. A., F. Fuentes, et al. (2003). "A reduction in dietary saturated fat decreases body fat content in overweight, hypercholesterolemic males." Nutr Metab Cardiovasc Dis 13(5): 273-7.

            BACKGROUND AND AIM: The effect of the quality of dietary fat on body composition is unknown. Our objective was to determine whether body composition is modified by the isocaloric substitution of a diet rich in saturated fat by a diet high in monounsaturated fat (Mediterranean diet) or a carbohydrate-rich diet in overweight subjects with hypercholesterolemia. METHODS AND RESULTS: The study involved 34 hypercholesterolemic males aged 18-63 years with a body mass index (BMI) of 28.2 (2.6), all of whom consumed a diet rich in saturated fat (SAT) for 28 days. They were then randomly divided into two groups of 17 subjects and underwent two dietary periods of 28 days each in a crossover design: a Mediterranean diet high in monounsaturated fat (MONO) and a carbohydrate-rich diet (CHO). The order of the diets was different for the two group. The CHO diet contained 57% CHO and 28% total fat (< 10% saturated fat, 12% monounsaturated fat and 6% polyunsaturated fat); the Mediterranean diet contained 47% CHO and 38% fat (< 10% saturated fat, 22% monounsaturated fat--75% of which was provided by olive oil- and 6% polyunsaturated fat). The variables measured at the end of each dietary intervention period were: 1) body composition by means of bioelectrical impedance; 2) plasma lipoproteins using enzymatic techniques; and 3) fatty acids in cholesterol esters by means of gas chromatography. BMI and the waist/hip ratio remained the same during the three dietary periods. A decrease in fat was observed when changing from a saturated fat diet (23.3 (6.3) kg) to a Mediterranean diet (20.8 (7.2) kg) (p < 0.05), or a carbohydrate-rich diet (20.6 (6.7) kg) (p < 0.05). Lean mass increased when changing from a SAT diet (58.4 (7.0) kg) to a CHO diet (60.2 (7.0) kg) (p < 0.05). CONCLUSION: The isocaloric substitution of a saturated fat-rich diet by a Mediterranean or carbohydrate-rich diet decreases total body fat in hypercholesterolemic males.


Ferdinandusse, S., S. Denis, et al. (2003). "Studies on the metabolic fate of n-3 polyunsaturated fatty acids." J Lipid Res 44(10): 1992-7.

            Several different processes involved in the metabolic fate of docosahexaenoic acid (DHA, C22:6n-3) and its precursor in the biosynthesis route, C24:6n-3, were studied. In cultured skin fibroblasts, the oxidation rate of [1-14C] 24:6n-3 was 2.7 times higher than for [1-14C]22:6n-3, whereas [1-14C]22:6n-3 was incorporated 7 times faster into different lipid classes than was [1-14C]24:6n-3. When determining the peroxisomal acyl-CoA oxidase activity, similar specific activities for C22:6(n-3)-CoA and C24:6(n-3)-CoA were found in mouse kidney peroxisomes. Thioesterase activity was measured for both substrates in mouse kidney peroxisomes as well as mitochondria, and C22:6(n-3)-CoA was hydrolyzed 1.7 times faster than C24:6(n-3)-CoA. These results imply that the preferred metabolic fate of C24:6(n-3)-CoA, after its synthesis in the endoplasmic reticulum (ER), is to move to the peroxisome, where it is beta-oxidized, producing C22:6(n-3)-CoA. This DHA-CoA then preferentially moves back, probably as free fatty acid, to the ER, where it is incorporated into membrane lipids.


Feoli, A. M., C. Roehrig, et al. (2003). "Serum and liver lipids in rats and chicks fed with diets containing different oils." Nutrition 19(9): 789-93.

            OBJECTIVES: Because dietary fat composition is determinant for serum cholesterol level, which is related to cardiovascular disease, we evaluated the effects of diets containing saturated (coconut oil) or polyunsaturated fatty acids (soybean oil) supplemented or not with dietary cholesterol on serum and liver lipid composition in two animal species. METHODS: Male Wistar rats (21 d old) were assigned to one of seven groups and fed with commercial diet or diets containing 5% or 20% soybean oil or 20% coconut oil with or without 1% cholesterol. Chicks were assigned to one of four groups and fed with diets containing 15% soybean oil or 15% coconut oil with or without 1% cholesterol. RESULTS: In rats, the accumulations of hepatic cholesterol and triacylglycerols were higher in the group fed 20% soybean oil and 1% cholesterol than in the group fed 20% coconut fat and 1% cholesterol. The highest serum levels of cholesterol and triacylglycerols were observed in the group fed coconut oil and cholesterol, compared with the group fed soybean oil and cholesterol. Triacylglycerol, high-density lipoprotein, and total cholesterol serum levels increased with diet containing coconut oil and cholesterol. In chicks, the highest hepatic cholesterol accumulation occurred in the group fed 15% coconut fat and 1% cholesterol. Total and high-density lipoprotein cholesterol levels increased with diet containing coconut oil and cholesterol, although none of these diets modified serum triacylglycerol levels. CONCLUSIONS: The type of experimental animal model and the diet composition influence lipid metabolism.


Feller, S. E., K. Gawrisch, et al. (2003). "Rhodopsin exhibits a preference for solvation by polyunsaturated docosohexaenoic acid." J Am Chem Soc 125(15): 4434-5.


Feher, J., A. Papale, et al. (2003). "Mitotropic compounds for the treatment of age-related macular degeneration. The metabolic approach and a pilot study." Ophthalmologica 217(5): 351-7.

            Recent histopathologic studies have shown that mitochondria and peroxisomes of the retinal pigment epithelium may play a central role in the pathophysiology of age-related macular degeneration (AMD). We supposed that compounds which improve mitochondrial functions (mitotropic compounds) may show beneficial effects in preventing AMD. Fourteen patients affected by early AMD were treated with a mixture containing acetyl-L-carnitine (ALC), polyunsaturated fatty acids (PUFAs), coenzyme Q10 (CoQ10) and vitamin E, while an equal number of age- and sex-matched patients affected by early AMD were treated with vitamin E only. Recovery time after macular photostress, foveal sensitivity and mean defect in the visual field as well as blood lipid levels were recorded at the beginning and after 3, 6, 9, 12 and 24 months of follow-up. In the treated group, all the visual functions showed slight improvement which was evident after 3 months of treatment and remained nearly stationary by the end of 24 months. The same tests in the control group showed slow worsening. The divergence between treated and control groups became more marked with time, but the difference was not significant at any time of the follow-up. These findings suggest that the blend of ALC, PUFA, CoQ10 and vitamin E may improve retinal functions in early AMD.


Farina, M., F. A. Soares, et al. (2003). "In vitro effects of selenite and mercuric chloride on liver thiobarbituric acid-reactive substances and non-protein thiols from rats: influences of dietary cholesterol and polyunsaturated and saturated fatty acids." Nutrition 19(6): 531-5.

            OBJECTIVE: We measured the in vitro effects of mercuric chloride (Hg2+) and selenite (Se4+) on hepatic 2-thiobarbituric acid-reactive substances (TBARS) and non-protein sulfhydryl (NPSH) levels of rats fed diets enriched with polyunsaturated or saturated fatty acids with and without cholesterol. METHODS: Male Wistar rats (21 d old) were assigned to one of four groups and fed diets containing 20% soybean oil, 20% soybean oil plus 1% cholesterol, 20% coconut oil, or coconut oil plus 1% cholesterol. After the feeding period (6 wk), body weight gain was equal in all groups. TBARS levels and NPSH content were measured after in vitro exposure to mercuric chloride (100 microM) and sodium selenite (25 microM) for 1 h. RESULTS: The lipid peroxidation, measured as TBARS levels in the control group, were statistically higher in hepatic homogenates of rats fed diets containing soybean oil than in groups fed coconut oil (P = 0.009). However, cholesterol supplementation did not change TBARS levels. Selenite alone did not modify TBARS production, whereas mercury alone significantly increased TBARS levels. Moreover, Se4+ protected against mercury-induced lipid peroxidation only in rats fed diets containing coconut oil. In the control group, dietary fat acids did not change NPSH levels. Selenite produced higher oxidative effects toward NPSH content, whereas Hg2+ decreased NPSH levels only in liver from rats fed diets containing soybean oil. NPSH levels were higher after concomitant exposure to Se4+ and Hg2+ chloride that after exposure to Se4+ alone, suggesting an interaction between Hg2+ and Se4+. Catalase activity was higher in animals fed diets containing soybean oil. Dietary cholesterol decreased glutathione peroxidase activity. CONCLUSION: Together these results indicated that the protective effect of Se4+ against mercury-induced lipid peroxidation depends on dietary fat saturation.


Fan, Y. Y., D. N. McMurray, et al. (2003). "Dietary (n-3) polyunsaturated fatty acids remodel mouse T-cell lipid rafts." J Nutr 133(6): 1913-20.

            In vitro evidence indicates that (n-3) polyunsaturated fatty acids (PUFA) suppress T-cell activation in part by displacing proteins from lipid rafts, specialized regions within the plasma membrane that play an important role in T-cell signal transduction. However, the ability of (n-3) PUFA to influence membrane microdomains in vivo has not been examined to date. Therefore, we compared the effect of dietary (n-3) PUFA on raft (liquid ordered) vs. soluble (liquid disordered) microdomain phospholipid composition in mouse T cells. Mice were fed diets containing either 5 g/100 g corn oil (control) or 4 g/100 g fish oil [contains (n-3) PUFA] + 1 g/100 g corn oil for 14 d. Splenic T-cell lipid rafts were isolated by density gradient centrifugation. Raft sphingomyelin content (mol/100 mol) was decreased (P < 0.05) in T cells isolated from (n-3) PUFA-fed mice. Dietary (n-3) PUFA were selectively incorporated into T-cell raft and soluble membrane phospholipids. Phosphatidylserine and glycerophosphoethanolamine, which are highly localized to the inner cytoplasmic leaflet, were enriched to a greater extent with unsaturated fatty acids compared with sphingomyelin, phosphatidylinositol and glycerophosphocholine. These data indicate for the first time that dietary (n-3) PUFA differentially modulate T-cell raft and soluble membrane phospholipid and fatty acyl composition.


Fan, Y. Y., T. E. Spencer, et al. (2003). "Chemopreventive n-3 fatty acids activate RXRalpha in colonocytes." Carcinogenesis 24(9): 1541-8.

            The underlying mechanisms by which n-3 polyunsaturated fatty acids (PUFA) exert a chemopreventive effect in the colon have not been elucidated. Retinoid X receptors (RXR) are a family of nuclear receptors implicated in cancer chemoprevention. Since docosahexaenoic acid (DHA), an n-3 PUFA enriched in fish oil, reduces colonocyte proliferation and enhances apoptosis relative to n-6 PUFA-treated cells, we determined whether DHA can serve as a specific ligand for RXRalpha activation relative to n-6 PUFA in colonocytes. In a mammalian one-hybrid assay, immortalized young adult mouse colonic (YAMC) cells were co-transfected with a yeast galactose upstream activating sequence (UAS)4-tk-Luciferase (Luc) reporter plasmid, plus either GAL4 DNA-binding domain fused to RXRalpha, retinoic acid receptor alpha or GAL4 alone, followed by an n-3, n-6 or n-9 fatty acid incubation. Luc activity levels were dose-dependently elevated only in n-3 PUFA (DHA)-treated RXRalpha. Since RXR homodimers and RXR/peroxisome proliferator-activated receptor (PPAR) heterodimers bind consensus direct repeat (DR1) motifs, YAMC and NCM460 (a normal human colonic cell line), were respectively, co-transfected with RXRalpha and DR1-Luc, followed by different PUFA treatment. Luc activity levels were increased (P < 0.05) only in DHA groups. The DHA-dependent induction of DR-1-Luc was reduced to basal levels upon RXRalpha antagonist-treatment, with no effect on PPARgamma antagonist-treatment. A role for select RXR isoforms in colonocyte biology was also determined by examining nuclear receptor mRNA levels in rat colon following dietary lipid and carcinogen exposure over time. RXRalpha, RXRbeta and RXRgamma were detected in rat colonic mucosa, and the levels of RXRalpha and RXRgamma were elevated in fish oil (n-3 PUFA) versus corn oil (n-6 PUFA) fed animals after 16 weeks. These data indicate that, RXRalpha, an obligatory component of various nuclear receptors, preferentially binds n-3 PUFA in colonocytes, and that the nuclear receptor targets for PUFA in the colon are modulated by dietary lipid exposure.


Eynard, A. R. and C. B. Lopez (2003). "Conjugated linoleic acid (CLA) versus saturated fats/cholesterol: their proportion in fatty and lean meats may affect the risk of developing colon cancer." Lipids Health Dis 2(1): 6.

            In spite of the considerable amount of experimental, clinical and epidemiological research about the consumption of red meat, total fats, saturated/unsaturated fatty acids and cholesterol with regard to the risk of developing colorectal cancer (CRC), the issue remains controversial. The general belief is a reduction of red meat intake, and subsequent nutritional advice usually strongly recommends this. Paradoxically, beef together with whole milk and dairy derivatives, are almost the only sources for conjugated linoleic acid (CLAs) family. Furthermore CLAs are the only natural fatty acids accepted by the National Academy of Sciences of USA as exhibiting consistent antitumor properties at levels as low as 0.25 - 1.0 per cent of total fats. Beside CLA, other polyunsaturated fatty acids (PUFA) belonging to the essential fatty acid (EFA) n-3 family, whose main source are fish and seafood, are generally believed to be antipromoters for several cancers. The purpose of this work is to critically analyze the epidemiological and experimental evidence by tentatively assuming that the reciprocal proportions of saturated fats (SA) plus cholesterol (CH) versus CLAs levels in fatty or lean beef may play an antagonistic role underlying the contradictory effects reported for red meats consumption and CRC risk. Recent results about meat intake and risk for CRC in Argentina have shown an unexpected dual behaviour related to the type of meats. Fatty meat derivatives, such as cold cuts and sausages, mainly prepared from fatty beef (up to 37% fat) were associated with higher risk, whereas high consumption of lean beef (< 15% fat) behaved as a protective dietary habit. CLA is located in the interstitial, non-visible, fat evenly distributed along muscle fibres as well as in subcutaneous depots. Visible fat may be easily discarded during the meal, whereas interstitial fats will be eaten. The remaining intramuscular fat in lean meats range from 25 to 50 g/Kg (2.5 to 5%). The proportion of CLA/SA+CH for lean beef eaters is 0.09 and the fatty mets 0.007 (g/100 g). As a consequence, the beneficial effects of minor amounts of CLA may be relatively enhanced in lean meat compared to fatty meat sub-products which contain a substantial amount of saturated fatty acids and cholesterol, as in cold cuts and cow viscera.


Evans, D. R., V. V. Parikh, et al. (2003). "Red blood cell membrane essential fatty acid metabolism in early psychotic patients following antipsychotic drug treatment." Prostaglandins Leukot Essent Fatty Acids 69(6): 393-9.

            A role of indices of oxidative stress, oxidative injury, and abnormal membrane phospholipid, specifically the phospholipid essential polyunsaturated fatty acids (EPUFAs) metabolism has been suggested based on studies in separate groups of patients with or without medication. The current study investigated the relationship between these biochemical measures in first-episode psychotic patients (N=16) at baseline and after 6 months of antipsychotic treatment (N=5 each with risperidone and olanzapine) and compared them to matched normal subjects. The indices of oxidative stress included: antioxidant enzymes; superoxide dismutase, glutathione peroxidase and catalase; and the oxidative injury as the levels of plasma lipid peroxides. The key membrane EPUFA's been; linolenic acid, arachidonic acid, nervonic acid, docosapentaenoic acid and docosahexaenoic acid. Furthermore, the changes in these biochemical measures were correlated with clinical symptomatology. Data indicated that, at baseline, reduced levels of antioxidant enzymes were associated with increased plasma lipid peroxides and reduced membrane EPUFAs, particularly omega-3 fatty acids. Furthermore, these biochemical measures normalized after 6 months of antipsychotic treatment. Parallel-improved psychopathology indicated that membrane EPUFA status might be partly affected by oxidative damage, which together may contribute to the pathophysiology and thereby, psychopathology of schizophrenia. These data also support the augmentation of antipsychotic treatment by supplementation with a combination of antioxidants and omega-3 fatty acids.


Estevez, M., D. Morcuende, et al. (2003). "Analysis of volatiles in meat from Iberian pigs and lean pigs after refrigeration and cooking by using SPME-GC-MS." J Agric Food Chem 51(11): 3429-35.

            The volatile compounds generated in meat from Iberian and lean pigs after four different treatments (raw, refrigerated, cooked, and refrigerated cooked meat) were analyzed. The different treatments showed different volatile profiles. Methyl alcohols and ketones (such as 2-ethyl-hexan-1-ol, 2-methyl-butan-1-ol, 3-methyl-butan-1-ol, and 3-hydroxy-butan-2-one) were the most representative in refrigerated meat because of the degradation of carbohydrates and proteins together with the Strecker degradation pathway. Lipid-derived volatiles were the most abundant in cooked meat and refrigerated cooked meat. Meat from different pig breeds presented different volatile profiles, probably due to different enzymatic and oxidative deterioration susceptibility. Otherwise, the fat content and its compositional characteristics also played an important role in the generation of volatiles. As compared to samples from lean pigs, muscles from Iberian pigs showed a higher content of heme iron that may have promoted the generation of higher content of total lipid-derived volatiles during the refrigeration of cooked meat. Despite that, the formation of volatiles with low thresholds and related to intense rancidity perception likely to be derived from polyunsaturated fatty acids was higher in lean pork than in meat from Iberian pigs. This might be expected to lead to a more intense development of a warmed over flavor during refrigeration of cooked samples from lean pigs.


Estabrook, R. W. (2003). "A passion for P450s (rememberances of the early history of research on cytochrome P450)." Drug Metab Dispos 31(12): 1461-73.

            Many members of the superfamily of hemeproteins, known as cytochrome P450 (P450 or CYP), are currently described in the literature (over 2000 at the date of this writing) [see Nelson, 2003 (http://drnelson.utmem.edu/CytochromeP450.html)]. In mammalian tissues, the P450s play central roles in drug and xenobiotic metabolism as well as steroid hormone synthesis, fat-soluble vitamin metabolism, and the conversion of polyunsaturated fatty acids to biologically active molecules. P450s also play a major role in plants by catalyzing the synthesis of a large number of secondary metabolites. Today we appreciate the unique oxygen chemistry catalyzed by the P450 enzymes as well as the dramatic effect of protein structural changes resulting in modifications of substrate specificity. Recent scientific advances have shown the importance of genetic differences (polymorphisms) in altering the physiological response of an animal to endo- and exo-biotic chemicals. In many instances these changes can be directly attributed to small differences in the amino acid sequence of a P450. The present article describes some of the early events associated with the establishment of the biological function of P450s. The 1950s and 1960s showed the transition of P450 from an unknown spectroscopic curiosity to the major player it now occupies in maintaining cellular homeostasis. The P450s are now recognized to occupy a great variety of phylogenetically distributed isoform activities. Much has been learned about the P450s, but much more remains as poorly understood. It has been almost 50 years since this class of unique proteins were discovered and their catalytic functions characterized. The present article describes the background and early history of research leading to our present knowledge of the cytochromes P450. Hopefully we will learn lessons from this history as we venture forward down the path of future scientific discovery.


Escudero, I., J. Martinez-Gonzalez, et al. (2003). "Experimental and interventional dietary study in humans on the role of HDL fatty acid composition in PGI2 release and Cox-2 expression by VSMC." Eur J Clin Invest 33(9): 779-86.

            BACKGROUND: High-density lipoproteins (HDLs) induce prostacyclin (PGI2) release in vascular smooth muscle cells (VSMCs) by up-regulation of cyclooxygenase-2 (Cox-2). Our goal was to analyze the role of human HDL lipid moiety on Cox-2-dependent PGI2 synthesis in human VSMCs and to assess the impact that the intake of diets with different fatty acid composition exert on HDL-induced PGI2 release. MATERIALS AND METHODS: Human VSMCs were treated with HDL or fatty acids in the presence or absence of different cell signalling inhibitors and PGI2 (by enzyme immunoassay) and Cox-2 protein levels (by Western blot) were analyzed. High-density lipoproteins were obtained from a plasma pool or from plasma of 12 volunteers subjected to a longitudinal dietary interventional study of three consecutive diets periods enriched in monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids n-6 (PUFA n-6) or n-3 (PUFA n-3). RESULTS: High-density lipoprotein delipidation attenuated the effect of HDL on both PGI2 synthesis and Cox-2 up-regulation, while arachidonic acid (AA) but not other fatty acids mimicked the effects of HDL. Arachidonic acid induced PGI2 synthesis and Cox-2 expression through similar mechanisms to those activated by HDL [pertussis toxin-sensitive G proteins, p42/44 mitogen-activated protein kinase (MAPK), p38MAPK, and c-Jun N-terminal kinase-1 (JNK-1) pathways]. Finally, we observed that HDL from the PUFA n-3 dietary period induced lower PGI2 release than that from the PUFA n-6 period (64% vs. 100%). CONCLUSIONS: Our results suggest that lipid moiety modulates HDL-induced PGI2 release/Cox-2 up-regulation in human VSMCs, and that changes in fatty acids as accomplished with the diet can modulate vascular PGI2 homeostasis.


Escriba, P. V., J. M. Sanchez-Dominguez, et al. (2003). "Alteration of lipids, G proteins, and PKC in cell membranes of elderly hypertensives." Hypertension 41(1): 176-82.

            In this study, we quantified the levels of lipids and signaling proteins in erythrocyte membranes from elderly normotensive and hypertensive subjects. In hypertensive subjects, the cholesterol/phospholipid ratio increased significantly in erythrocyte membranes, owing to the reduction of phospholipid levels concomitant with a rise in the levels of cholesterol. In addition, differences were also found in the amount of fatty acids in both phospholipid and cholesterol esters. Erythrocyte membranes from hypertensive subjects contained higher levels of monounsaturated and lower levels of polyunsaturated fatty acids. On the other hand, signaling proteins such as G proteins and protein kinase C have been implicated in the control of blood pressure. Previous studies have shown that the cellular localization and the activity of these proteins are modulated by the type and the abundance of membrane lipids. For this reason, we assessed the levels of these signaling molecules in the membrane. We found that the levels of membrane-associated (active/preactive) G proteins (Galpha(i), Galpha(o), and Gbeta) and protein kinase C were significantly reduced in hypertensive subjects. We believe that these alterations could be related to the etiopathology of hypertension in elderly subjects or alternatively may correspond to adaptive compensatory mechanisms.


Enjalbert, F., P. Eynard, et al. (2003). "In vitro versus in situ ruminal biohydrogenation of unsaturated fatty acids from a raw or extruded mixture of ground canola seed/canola meal." J Dairy Sci 86(1): 351-9.

            Raw or extruded blends of ground canola seeds and canola meal were used to compare in vitro and in situ lag times and rates of disappearance due to ruminal biohydrogenation of unsaturated fatty acids. The in situ study resulted in higher lag times for biohydrogenation for polyunsaturated fatty acids and lower rates of biohydrogenation of unsaturated fatty acids than the in vitro study, so the in situ biohydrogenation of polyunsaturated fatty acids was not complete at 24 h of incubation. With both methods, rates of biohydrogenation of polyunsaturated fatty acids were higher than for cis-delta9C18:1. Extrusion did not affect the rate of biohydrogenation of cis-delta9C18:1, but resulted in higher rates of biohydrogenation of polyunsaturated fatty acids with higher proportions of trans intermediates of biohydrogenation at 4 h of incubation in vitro and at 8 h of incubation in situ. These results suggest that extrusion affects the isomerization of polyunsaturated fatty acids, rather than the hydrogenation steps. In conclusion, in vitro and in situ methods can both show differences of ruminal metabolism of unsaturated fatty acids due to processing, but the methods provide very different estimates of the rates of disappearance due to biohydrogenation.


Engstrom, K., R. Wallin, et al. (2003). "Effects of Scandinavian caviar paste enriched with a stable fish oil on plasma phospholipid fatty acids and lipid peroxidation." Eur J Clin Nutr 57(9): 1052-9.

            OBJECTIVE: To study the possibility of increasing the very long-chain n-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in humans by means of consumption of a common food product, Scandinavian caviar paste, suitable for strategic enrichment with a high concentration of these fatty acids, and to measure the potential inducement of lipid peroxidation. DESIGN: A randomized double blind repeated measures experiment. SUBJECTS AND INTERVENTIONS: In total, 16 healthy, nonsmoking subjects (eight men and eight women, age 42+/-12 y) were included in the study. Eight consumed 25 g ordinary caviar paste daily for 3 weeks, and eight the same amount of caviar paste enriched with a very stable fish oil (7%, wt/wt). Blood lipids, plasma phospholipid fatty acids and lipid peroxidation were measured. RESULTS: alpha-Linoleic acid was significantly decreased after intake of both ordinary (-8%, P<0.05) and fish oil caviar (-10%, P<0.05), as was the sum of all n-6 fatty acids (-6%, P<0.05 and -8%, P<0.001, respectively). The fatty acids EPA and DHA, as well as the sum of all n-3 fatty acids, increased significantly in both caviar groups but more in the group given fish oil caviar paste (EPA: +51%, P<0.05 and +100%, P<0.001, respectively; DHA: +24%, P<0.01 and +29%, P<0.001, respectively; sum of n-3:+27%, P<0.05 and +40%, P<0.001, respectively). Lipid peroxidation, measured as the thiobarbituric acid-malondialdehyde adduct, was increased by 26% (P<0.05) after intake of ordinary caviar paste, but was unchanged after intake of fish oil-enriched caviar paste. CONCLUSION: Scandinavian caviar paste is a spread naturally enriched with n-3 polyunsaturated fatty acids that can be included in the diet to achieve an increase in these fatty acids. However, changing to caviar paste enriched with stable fish oil will lead to a considerably greater increase in EPA and DHA. SPONSORSHIP: Swedish Medical Research Council; Cardinova AB, Uppsala, Sweden.


Emsley, R., P. Oosthuizen, et al. (2003). "Clinical potential of omega-3 Fatty acids in the treatment of schizophrenia." CNS Drugs 17(15): 1081-91.

            The phospholipids in the neuronal membranes of the brain are rich in highly unsaturated essential fatty acids (EFAs). It has been hypothesised that abnormalities of phospholipid metabolism are present in patients with schizophrenia and that the EFAs omega-3 polyunsaturated fatty acids, and eicosapentaenoic acid (EPA) in particular, may have a role in treating this illness. Considerable preclinical and clinical evidence provides support for this proposal. An epidemiological study reported a better outcome for patients with schizophrenia in countries where the diet is rich in unsaturated fatty acids. Evidence of abnormalities of EFAs has been found in erythrocyte membranes and cultured skin fibroblasts of patients with schizophrenia, and abnormal retinal function and niacin skin flush tests (markers of omega-3 polyunsaturated fatty acid depletion) have also been reported. Case reports and an open-label clinical trial reported efficacy for EPA in schizophrenia. Four randomised, controlled trials of EPA versus placebo as supplemental medication have now been reported. Two of these trials showed significant benefit with EPA on the positive and negative symptom scale total scores, whereas the other two did not show any effects on this primary efficacy measure. One study also reported a beneficial effect on dyskinesia. In the only published trial in which EPA was used as monotherapy versus placebo in schizophrenia, some evidence was found to suggest antipsychotic activity. Taken together, there is considerable evidence to suggest abnormalities of EFAs in cell membranes of patients with schizophrenia, and there is preliminary evidence that EPA is an effective adjunct to antipsychotics.


Eldho, N. V., S. E. Feller, et al. (2003). "Polyunsaturated docosahexaenoic vs docosapentaenoic acid-differences in lipid matrix properties from the loss of one double bond." J Am Chem Soc 125(21): 6409-21.

            Insufficient supply to the developing brain of docosahexaenoic acid (22:6n3, DHA), or its omega-3 fatty acid precursors, results in replacement of DHA with docosapentaenoic acid (22:5n6, DPA), an omega-6 fatty acid that is lacking a double bond near the chain's methyl end. We investigated membranes of 1-stearoyl(d(35))-2-docosahexaenoyl-sn-glycero-3-phosphocholine and 1-stearoyl(d(35))-2-docosapentaenoyl-sn-glycero-3-phosphocholine by solid-state NMR, X-ray diffraction, and molecular dynamics simulations to determine if the loss of this double bond alters membrane physical properties. The low order parameters of polyunsaturated chains and the NMR relaxation data indicate that both DHA and DPA undergo rapid conformational transitions with correlation times of the order of nanoseconds at carbon atom C(2) and of picoseconds near the terminal methyl group. However, there are important differences between DHA- and DPA-containing lipids: the DHA chain with one additional double bond is more flexible at the methyl end and isomerizes with shorter correlation times. Furthermore, the stearic acid paired with the DHA in mixed-chain lipids has lower order, in particular in the middle of the chain near carbons C(10)(-)(12), indicating differences in the packing of hydrocarbon chains. Such differences are also reflected in the electron density profiles of the bilayers and in the simulation results. The DHA chain has a higher density near the lipid-water interface, whereas the density of the stearic acid chain is higher in the bilayer center. The loss of a single double bond from DHA to DPA results in a more even distribution of chain densities along the bilayer normal. We propose that the function of integral membrane proteins such as rhodopsin is sensitive to such a redistribution.


El-Assaad, W., J. Buteau, et al. (2003). "Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death." Endocrinology 144(9): 4154-63.

            We have proposed the "glucolipotoxicity" hypothesis in which elevated free fatty acids (FFAs) together with hyperglycemia are synergistic in causing islet beta-cell damage because high glucose inhibits fat oxidation and consequently lipid detoxification. The effects of 1-2 d culture of both rat INS 832/13 cells and human islet beta-cells were investigated in medium containing glucose (5, 11, 20 mM) in the presence or absence of various FFAs. A marked synergistic effect of elevated concentrations of glucose and saturated FFA (palmitate and stearate) on inducing beta-cell death by apoptosis was found in both INS 832/13 and human islet beta-cells. In comparison, linoleate (polyunsaturated) synergized only modestly with high glucose, whereas oleate (monounsaturated) was not toxic. Treating cells with the acyl-coenzyme A synthase inhibitor triacsin C, or the AMP kinase activators metformin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside that redirect lipid partitioning to oxidation, curtailed glucolipotoxicity. In contrast, the fat oxidation inhibitor etomoxir, like glucose, markedly enhanced palmitate-induced cell death. The data indicate that FFAs must be metabolized to long chain fatty acyl-CoA to exert toxicity, the effect of which can be reduced by activating fatty acid oxidation. The results support the glucolipotoxicity hypothesis of beta-cell failure proposing that elevated FFAs are particularly toxic in the context of hyperglycemia.


Eitel, K., H. Staiger, et al. (2003). "Protein kinase C delta activation and translocation to the nucleus are required for fatty acid-induced apoptosis of insulin-secreting cells." Diabetes 52(4): 991-7.

            Insulin resistance as well as pancreatic beta-cell failure can be induced by elevated free fatty acid (FFA) levels. We studied the mechanisms of FFA-induced apoptosis in rat and human beta-cells. Chronic treatment with high physiological levels of saturated fatty acids (palmitate and stearate), but not with monounsaturated (palmitoleate and oleate) or polyunsaturated fatty acids (linoleate), triggers apoptosis in approximately 20% of cultured RIN1046-38 cells. Apoptosis restricted to saturated FFAs was also observed in primary cultured human beta-cells, suggesting that this mechanism is potentially relevant in vivo in humans. To further analyze FFA-induced signaling pathways leading to apoptosis, we used RIN1046-38 cells. Apoptosis was accompanied by a rapid (within 15 min) nuclear translocation of protein kinase C (PKC)-delta and subsequent lamin B1 disassembly. This translocation was impaired by the phospholipase C inhibitor U-73122, which also substantially reduced apoptosis. Furthermore, lamin B1 disassembly and apoptosis were decreased by cell transfection with a dominant-negative mutant form of PKC-delta. These data suggest that nuclear translocation and kinase activity of PKC-delta are both necessary for saturated fatty acid-induced apoptosis.