Effect of polyunsaturated fatty acids of the n-3 and n-6 series on lipid composition and eicosanoid synthesis of platelets and aorta and on immunological induction of atherosclerosis in rabbits

The effect of dietary fish oil (rich in n-3 polyunsaturated fatty acids (PUFA], corn oil (rich in n-6 PUFA) and coconut oil (low in n-3 and n-6 PUFA) on the induction of atherosclerosis by serum sickness in rabbits was investigated over a 12-month period. Dietary fish oil led to a significant increase in the level of eicosapentaenoic acid (EPA) in all platelet phospholipid fractions and to a significant reduction in the level of platelet phosphatidylethanolamine arachidonic acid (AA). In aortic total phospholipids, rabbits given fish oil showed a significant reduction in AA and a significant increase in EPA. Rabbits given fish oil showed significantly lower collagen-induced platelet thromboxane A2 release and aortic production of 6-keto-PGF1 alpha. Serum total immune complex levels and anti-horse serum IgG levels were not influenced by diet. There was a significant reduction in total aortic atherosclerosis in fish oil-fed animals compared with coconut oil fed animals.     

Ethanol-induced changes in lipid composition of intestinal microvillus membrane in rats fed different dietary fats

BACKGROUND/METHOD: The effect of feeding ethanol for 5 weeks on the lipid composition of the intestinal microvillus membrane (MVM) was studied in rats fed a commercial rat pellet (RP) diet or purified diets containing 10% coconut oil (CCO), corn oil (CO) or fish oil (FO). RESULTS: A low cholesterol/phospholipid ratio and increased saturated fatty acid level were observed in MVM from the CCO or FO groups. Chronic administration of ethanol to RP- or CO-fed animals increased phospholipids, total and free cholesterol, and the triglyceride and ganglioside content of MVM. The free cholesterol and phospholipid content was reduced while the triglyceride level remained unaffected by ethanol treatment in the CCO or FO groups. Ethanol ingestion decreased 10:2 and 20:4 (n-6 fatty acids) but increased the saturated fatty acid content of MVM in all the dietary groups except in CCO-fed animals where the 18:2 level was not affected. An elevated 18:1, but decreased 22:6 percentage was observed in the ethanol-fed FO group. The fatty acid composition of MVM from the CCO-fed group was least affected by ethanol treatment. CONCLUSION: These observations suggest that the type of dietary fat modifies ethanol-mediated alterations in MVM lipid composition.     

Comparative changes in the fatty-acid composition of rat cardiac phospholipids after long-term feeding of sunflower seed oil- or tuna fish oil-supplemented diets

The fatty-acid composition of rat heart phospholipids was examined after long-term, i.e. more than 12 months, feeding of diets supplemented with n-6 fatty acids as sunflower seed oil (SSO), or n-3 fatty acids as tuna fish oil (TFO) which is a particularly rich source of docosahexenoic acid (DHA). Although some small changes occurred in the relative proportions of palmitic and stearic acids and in the ratio of total saturates to total unsaturates, the most important changes were in the relative proportions of 18:2 n-6 and 20:4 n-6 to 20:5 n-3 and 22:6 n-3. In general, the n-6/n-3 ratio of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and diphosphatidyl glycerol (DPG) was altered in favour of the family of fatty acids administered, although the proportions of the individual long-chain polyunsaturated fatty acids which contributed to this ratio varied from one class of phospholipids to another. In cardiac PC and PE, feeding TFO supplements reduced the proportions of arachidonic acid (AA) and significantly elevated (p less than 0.01) the proportions of DHA but produced relatively little change in those of eicosapentenoic acid (EPA). In DPG, feeding TFO led to a significant increase in the proportion of AA as well as an increase in DHA. The level of EPA was relatively low in PC, PE and DPG even after TFO feeding and never reached comparable levels with that of either AA or DHA. Nevertheless the n-6/n-3 ratio in all these classes of major cardiac phospholipids was significantly reduced by feeding TFO compared to the SSO diet or the commercial rat chow (CC) reference group. In contrast to the reports of other workers who have studied the fatty-acid composition of platelet membranes after feeding various fish oil supplements, in the rat heart the major effect of tuna fish oil is an increase in the proportion of DHA rather than EPA in the cardiac phospholipids.     

Altered levels of n-6/n-3 fatty acids in rat heart and storage fat following variable dietary intake of linoleic acid

Fat-supplemented dies enriched with linoleic acid by the addition of 12% w/w sunflower seed oil or proportionally reduced in linoleic acid by addition of 12% mutton fat were fed to rats for 18 months before the fatty acid composition of perirenal storage fat and myocardial membranes (phospholipids) was determined. Although the fatty acid composition of perirenal fat generally reflected that of the diet, there was an inverse relationship between the consumption of n-6 and the deposition of n-9 fatty acids. In addition, enhanced deposition of oleic acid (18:1, n-9) appears to be related to the dietary intake of stearic acid (18:0). In contrast, in myocardial membranes the n-3 polyunsaturated fatty acids are found to be increased when the intake of n-6 polyunsaturated fatty acids is reduced. This is particularly evident for docosahexaenoic acid (22:6, n-3) which is significantly increased in phosphatidylcholine, phosphatidylethanolamine, and diphosphatidylglycerol fractions of myocardial membranes, when the mutton fat diet was fed. After feeding the sunflower seed oil diet, the increased consumption of linoleic acid produced only small changes in the 18:2, n-6 content of cardiac phosphatidylcholine and phosphatidylethanolamine. These major classes of membrane phospholipids also showed only small increases in 20:4, n-6. In diphosphatidylglycerol, increased 18:2, n-6 also followed increased dietary intake, but this was not accompanied by increased 20:4, n-6. These changes in myocardial phospholipid fatty acid composition are similar to those observed after short-term feeding reported previously and confirm that changes in dietary n-6/n-3 fatty acid intake affect the fatty acid composition of both myocardial membranes and storage fat. These changes persist for the duration of the feeding period.     

Effects of Prenatal Ethanol and Long-Chain n-3 Fatty Acid Supplementation on Development in Mice. 2. Fatty Acid Composition of Brain Membrane Phospholipids

Pregnant mice were fed equivalent daily amounts of a liquid diet containing 25% (kcal) ethanol, or with maltose dextrin substituted isocalorically for ethanol. The diet also contained 20% oil; this was either of two mixtures, one comprised of predominantly n-6 (18:2n-6) fatty acids, and the other containing an equivalent amount of n-6, but supplemented with a source of long chain n-3 (20:5n-3, 22:6n-3) fatty acids. An additional control group was fed lab chow ad libitum. The treatment was implemented from day 7 to 17 of gestation, whereafter all groups were fed lab chow. Birth occurred on day 19, and the fatty acid composition of the brain membrane phospholipids was determined in the pups 3 days after birth (day 22 postconception) and again, 10 days later (day 32 postconception). On day 22 the polyunsaturated fatty acid (PUFA) composition of the brain phospholipids reflected dietary availability, with the n-3/n-6 ratio higher in the n-3 groups; this was decreased by ethanol in the phosphatidylcholine (PC) fraction. The dietary effect was still apparent on day 32; again ethanol reduced this in both the PC and phosphatidylethanolamine (PE) fractions. The n-3 oil, but not ethanol, increased the 20:3n-6/20:4n-6 ratio, indicative of an inhibition of the activity of delta-5 desaturase. With respect to the 22:C compounds, the n-3 oil decreased the levels of 22:5n-6, while increasing those of 22:6n-3, but generally the sum of these two fatty acids remained unchanged. Ethanol decreased levels of 22:5n-6, and, on day 32, also decreased those of 22:6n-3, resulting in a decrease in the sum of these 22:C PUFA.     

Influence of different dietary fatty acid sources on erythrocyte lipids and plasma and liver essential fatty acids in hamsters fed ethanol

Hamsters fed ethanol were given three different dietary sources of essential fatty acids; safflower oil, evening primrose oil (both mainly n-6 fatty acids) or linseed oil (mainly n-3 fatty acids). After 7 weeks, plasma, erythrocyte and liver lipids and fatty acids were analyzed. Plasma and liver lipids were not significantly different in the ethanol-fed hamsters compared to the controls. Erythrocyte total phospholipid was increased only in the ethanol-fed groups given n-6 but not n-3 fatty acids. Some fatty acid changes induced by ethanol were predictable, e.g. lower 20:4 n-6 in hamsters fed n-6 fatty acids, but others were not predictable, e.g. higher 22:6 n-3 in all the ethanol-fed groups. The effect of ethanol on hamster lipids and fatty acid composition appears dependent on the predominant class of dietary fatty acids.     

Modification of the fatty acid composition of rat heart sarcolemma with dietary cod liver oil, corn oil or butter

The effect of dietary cod liver oil, corn oil or butter upon the lipid composition of cardiac sarcolemma and the activity of sarcolemmal Na+, K+ ATPase was examined in male Wistar rats. The cod liver oil diet caused significant changes in the fatty acid composition of the major phospholipids of sarcolemma, phosphatidyl choline and phosphatidyl ethanolamine. In both these phospholipids arachidonic acid, 20:4 (n - 6) was reduced by about 50% compared to rats fed butter or corn oil and was replaced by the (n - 3) fatty acids eicosapentaenoic and docosahexaenoic acids. The corn oil diet caused a significant diminution in the oleic acid content of phosphatidyl choline and elevation of linoleic acid in phosphatidyl ethanolamine. The phospholipid class composition, total phospholipid fatty acid content and cholesterol content of sarcolemma were not altered by the diets used. The activity of Na+, K+ ATPase in the cardiac sarcolemma was not significantly changed by the different diets.     

Fish oil fatty acids and experimental arthritis.

Maintenance of mice on dietary regimens containing fish oil decreases severity of collagen-induced arthritis. Macrophages from fish oil fed animals had decreased omega-6 and significant amounts of omega-3 polyunsaturated fatty acids in membrane phospholipids and produced significantly less prostaglandins than macrophages from corn oil fed animals. Gender differences in both prostaglandin production and susceptibility to arthritis were noted.     

Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis

OBJECTIVE: To determine the efficacy of fish oil derived (n-3) fatty acid supplementation (3-6 capsules/day) in subjects with rheumatoid arthritis (RA) whose (n-6) fatty acid intake in the background diet was < 10 g/day, compared to olive/corn oil capsule supplement over a 15 week period. METHODS: A placebo controlled, double blind, randomized 15 week study to determine the effect of supplementation on clinical variables in 50 subjects with RA whose background diet was naturally low in (n-6) fatty acids. Fish oil containing 60% (n-3) fatty acids was supplemented at a rate of 40 mg/kg body weight. RESULTS: Analysis of 9 clinical variables indicated there was a significant difference (p < 0.02) between control and treatment groups. Five subjects in the treatment group and 3 in the control group met the American College of Rheumatology 20% improvement criteria. Dietary supplementation resulted in a significant increase in eicosapentaenoic acid in plasma and monocyte lipids in the supplemented group. CONCLUSION: The findings suggest that fish oil supplementation that delivers (n-3) fatty acids at a dose of 40 mg/kg body weight/day, with dietary (n-6) fatty acid intake < 10 g/day in the background diet, results in substantial cellular incorporation of (n-3) fatty acids and improvements in clinical status in patients with RA.     

Lipid peroxidation in normoxic and ischaemic-reperfused hearts of fish oil and lard fat fed pigs

The in situ and in vitro rate of lipid peroxidation of hearts were determined in two groups of pigs which had been fed diets which differed only in fatty acid composition for 8 weeks. During the dietary period venous plasma levels of malondialdehyde and lipofuscin were not higher in pigs receiving the highly unsaturated fatty acid-containing mackerel oil than those receiving lard fat. Malondialdehyde was produced in the coronary system of the mackerel oil fed animals. After the heart was subjected to a sequence of short periods of ischaemia (5 min) and reperfusion (10 min), myocardial malondialdehyde production in the mackerel oil fed pigs did not increase. Contribution of prostaglandin synthesis products to myocardial malondialdehyde formation is probably of minor importance. Recovery of regional heart function after the ischaemic periods was similar for both dietary groups. In the phospholipids of sarcolemmal preparations isolated from the left ventricle of mackerel oil fed animals 18:2 n-6 and 20:4 n-6 were partially replaced by 20:5 n-3 and 22:6 n-3. Ischaemia-reperfusion did not alter sarcolemmal fatty acid composition and Ca2+ pumping ATPase activity. Sarcolemmal membrane from mackerel oil fed pigs exposed in vitro to a free radical generating system showed a higher malondialdehyde production than that from lard fat fed pigs. Thus, in spite of the increased susceptibility of heart membranes to free radical generated peroxidation in mackerel oil fed animals, recovery of left ventricular function was similar following multiple short-term periods of ischaemia.     

The fatty acid composition of chylomicrons influences the rate of their lipolysis in vivo

BACKGROUND AND AIMS: Previous work in our laboratory has shown that chylomicron triacylglycerol is lipolysed in vitro by lipoprotein lipase more rapidly when the particles are enriched with n-6 polyunsaturated as compared to saturated, monounsaturated or n-3 polyunsaturated fatty acids. It is possible, however, that this does not reflect the situation in vivo, where the active enzyme is bound to the vascular endothelium. The aim of the present study is to investigate the effect of the fatty acid composition of chylomicrons on their lipolysis in the rat in vivo. METHODS AND RESULTS: [3H]Oleate-labelled chylomicrons derived from palm, olive, corn or fish oil (enriched in saturated, monounsaturated, n-6 polyunsaturated and n-3 polyunsaturated fatty acids respectively) containing > 90% of the label in triacylglycerol were injected intravenously into functionally hepatectomised rats and blood samples were taken at time intervals up to 40 min. The radioactivity in serum triacylglycerol decreased significantly more rapidly when corn oil as compared to palm, olive or fish oil chylomicrons were used. Conversely, the radioactivity in serum free fatty acid derived from corn oil chylomicrons showed a faster increase than that derived from the other three types of particles. CONCLUSIONS: These results indicate that chylomicrons enriched with n-6 polyunsaturated fatty acids are converted to chylomicron remnants in vivo more rapidly than those enriched with saturated, monounsaturated or n-3 polyunsaturated fatty acids. This provides a partial explanation for the differential rate of removal from the blood of cholesterol carried in chylomicrons of different fatty acid composition demonstrated in previous work from this laboratory.     

Changes in dietary fatty acids modify the decreased lipolytic beta3-adrenergic response to hyperinsulinemia in adipocytes from pregnant and nonpregnant rats

The effect of dietary olive oil and fish oil on the lipolytic dose-response of the beta3-adrenergic agonists, epinephrine, isoproterenol, BRL-37344, and CGP-12177, in adipocytes was studied in pregnant and virgin rats either untreated or under hyperinsulinemic-euglycemic conditions. Rats were fed a semisynthetic diet containing 5% of either olive oil or fish oil and studied at day 20 of treatment and/or gestation. Plasma glucose was lower and plasma insulin, triglycerides, and free fatty acids (FFAs) were higher in pregnant versus virgin rats, and the insulin sensitivity index was lower in the former. Lumbar adipose tissue phospholipid fatty acids showed a significantly higher monounsaturated fatty acid and a lower (n - 3) fatty acid content in rats fed the olive oil diet versus the fish oil diet. The lipolytic dose-response curve of either adrenergic agent was always lower in adipocytes from untreated pregnant rats versus virgin rats, and whereas the hyperinsulinemic-euglycemic clamp decreased these responses in adipocytes from virgin rats fed the olive oil diet only, adipocytes from pregnant rats always showed a decreased dose-response lipolytic curve. Thus, the lipolytic responsiveness of beta3-adrenoceptor (beta3-AR) agonists by adipocytes is impaired in cells from rats made hyperinsulinemic chronically by pregnancy or acutely by the hyperinsulinemic-euglycemic clamp, but such response to the acute condition disappears when the adipocyte phospholipid composition is modified by changes in dietary fatty acids.     

Fatty acid and enzymatic compositional changes in the pancreas of rats fed dietary n-3 and n-6 polyunsaturated fatty acids

The influence of n-3 and n-6 PUFA on the fatty acid composition and the enzyme content of zymogen granules of the normal exocrine pancreas was tested on rats. The animals were fed on different diets comprising 5% fish oil (FO), safflower oil (SFO), and evening primrose oil (EPO) used singly or in combination as dietary fats. The results were compared with those from animals fed 5% hydrogenated beef tallow (HBT). The fatty acid composition and digestive enzyme content were analyzed after a 6-wk feeding period. Differences in the pancreatic fatty acid profiles were related to the fatty acid composition of the ingested fats. Equivalent levels of n-3 fatty acids and 20:3n-6 were obtained with either EPO or FO fed singly or in combination. Similar results were observed with SFO/FO. Higher C20:3n-6/C20:4n-6 ratios were obtained with the oil mixtures. An increase in amylase levels, but a decrease in serine protease (Band 21 kdalton) levels, was associated with EPO. An elevation in procarboxypeptidase levels paralleled an increase in 18:0 levels, whereas the proportion of lipase (Band 49 kdalton) varied inversely with the proportion of C20:3n-6. The SFO/FO mixture elevated the proportions of protease II and proelastase. These results suggest that specific fatty acids influence the proportion of specific digestive enzymes in the zymogen granules.     

Dietary fatty acids modify insulin secretion of rat pancreatic islet cells in vitro

The type of dietary fat affects the action of insulin by changes induced in the fatty acid composition of cell membranes. Little is known, however, about the effects of dietary fatty acids on insulin secretion or the possible relation between the fatty acid composition of the membrane phospholipids and insulin secretion. We therefore studied the effects of dietary fatty acids on insulin secretion stimulated by glucose, forskolin and arginine, and on the insulin content of isolated pancreatic islets, as well as on the fatty acid composition of muscle phospholipids, which were used as markers of the diet-induced modifications in the cell membranes. Five groups of rats were fed for one month with diets varying only in their fat composition: olive oil, sunflower oil, soybean oil, fish oil and palmitic acid (16:0) + soybean oil (SAT). The SAT group had higher insulin secretion, independently of the secretagogue used. No significant differences were found in insulin content between the groups. The dietary fatty acids modified the fatty acid composition of the muscle phospholipids, both in endogenously synthesized fatty acids and in those which were unable to be synthesized by the organism. No statistically significant relation was found between insulin secretion and the content of certain fatty acids in the muscle phospholipids.     

Enhanced level of n-3 fatty acid in membrane phospholipids induces lipid peroxidation in rats fed dietary docosahexaenoic acid oil

The effect of dietary docosahexaenoic acid (DHA, 22:6n-3) oil with different lipid types on lipid peroxidation was studied in rats. Each group of male Sprague-Dawley rats was pair fed 15% (w/w) of either DHA-triglycerides (DHA-TG), DHA-ethyl esters (DHA-EE) or DHA-phospholipids (DHA-PL) for up to 3 weeks. The palm oil (supplemented with 20% soybean oil) diet without DHA was fed as the control. Dietary DHA oils lowered plasma triglyceride concentrations in rats fed DHA-TG (by 30%), DHA-EE (by 45%) and DHA-PL (by 27%), compared to control. The incorporation of dietary DHA into plasma and liver phospholipids was more pronounced in the DHA-TG and DHA-EE group than in the DHA-PL group. However, DHA oil intake negatively influenced lipid peroxidation in both plasma and liver. Phospholipid peroxidation in plasma and liver was significantly higher than control in rats fed DHA-TG or DHA-EE, but not DHA-PL. These results are consistent with increased thiobarbituric acid reactive substances (TBARS) and decreased alpha-tocopherol levels in plasma and liver. In addition, liver microsomes from rats of each group were exposed to a mixture of chelated iron (Fe(3+)/ADP) and NADPH to determine the rate of peroxidative damage. During NADPH-dependent peroxidation of microsomes, the accumulation of phospholipid hydroperoxides, as well as TBARS, were elevated and alpha-tocopherol levels were significantly exhausted in DHA-TG and DHA-EE groups. During microsomal lipid peroxidation, there was a greater loss of n-3 fatty acids (mainly DHA) than of n-6 fatty acids, including arachidonic acid (20:4n-6). These results indicate that polyunsaturation of n-3 fatty acids is the most important target for lipid peroxidation. This suggests that the ingestion of large amounts of DHA oil enhances lipid peroxidation in the target membranes where greater amounts of n-3 fatty acids are incorporated, thereby increasing the peroxidizability and possibly accelerating the atherosclerotic process.     

Effects of Dietary Supplementation with n-6 and n-3 Long-chain Polyunsaturated Fatty Acids on Serum Lipoproteins and Platelet Function in Hypertriglyceridaemic Patients

ABSTRACT Twenty-seven patients with hypertriglyceridaemia were given dietary supplementation either with evening primrose oil rich in gammalinolenic acid (GLA, 18: 3 n-6) (n=13) or a marine oil concentrate containing n-3 fatty acids (n=14) in a double-blind cross-over design during 8+8 weeks with olive oil as placebo. During GLA supplementation, increases in GLA and dihomogammalinolenic acid (20: 3 n-6) were found in plasma lipid esters and platelet phospholipids, whereas platelet function and serum lipoproteins were unaffected. During supplementation with n-3 fatty acids there was a significant decrease in triglycerides in all lipoprotein fractions with a slight increase in high density lipoprotein and low density lipoprotein cholesterol. A marked increase in the long-chain n-3 fatty acids was found both in plasma and platelets, mainly at the expense of the n-6 fatty acids. No pronounced effects on platelet reactivity could be demonstrated. Our results confirm a triglyceride-lowering effect of n-3 fatty acids, whereas no such effect of GLA could be demonstrated.     

Dietary fatty acid supplementation alters stress reactivity and performance in man

Certain dietary polyunsaturated fatty acids, gamma linolenic (18:3n-6) and eicosapentaenoic (20:5n-3) acid, attenuate cardiovascular reactivity to stress in rats. To study their effects on cardiovascular reactivity to acute stress in man, 30 men were randomly assigned to one of three groups and given 28 day supplements of borage oil (containing 18:3n-6), fish oil (containing 20:5n-3), or olive oil (placebo). Reactivity to the Stroop colour-word conflict test was assessed prior to and following treatment. Borage oil alone attenuated blood pressure and heart rate responses to stress, increased skin temperature, and improved task performance. These data suggest that diet may be used to alter stress reactivity in man.     

Influence of dietary fat on the lipid composition of perirenal adipose tissue in rats

The influence of dietary fat on the composition of perirenal adipose tissue was studied in Wistar rats fed three experimental semisynthetic, isocaloric diets containing different qualities of fat (olive oil, butter and medium chain triglycerides + corn oil). Under these experimental conditions, the saturation index reflects the percentage of fatty acids supplied by each diet; this index was highest in animals fed the diet containing butter and lowest in the group in which olive oil was the dietary fat source. The amount of linoleic acid (the major component of the diunsaturation index) supplied by the diet is directly paralleled by levels of this fatty acid in perirenal adipose tissue, whereas the monounsaturation index in adipose tissues, considered an indicator of the dietary supply of monounsaturated fatty acids in the rat, failed to show a clearly proportional relationship between intake and perirenal adipose tissue levels.     

Alterations in the lipids and prostaglandins in mouse spleen following the ingestion of menhaden oil

Two groups of male mice were fed for 2 weeks with a semisynthetic diet supplemented with either 10% hydrogenated coconut oil or 10% menhaden oil. The spleen from animals fed with menhaden oil contained significantly higher amounts of polyunsaturated n-3 fatty acids. The n-3 fatty acids reciprocally replaced arachidonic acid in the phospholipids. The synthesis of 6-keto prostaglandin F1 alpha and prostaglandin E2 by spleen tissues were significantly depressed (70-80%) in mice consuming menhaden oil. These studies indicated that n-3 fatty acids can effectively displace arachidonic acid from spleen lipids and thereby affect the synthesis of prostaglandins. The implications of these observations are discussed.     

The role of n-3 polyunsaturated fatty acids in brain: modulation of rat brain gene expression by dietary n-3 fatty acids

Rats were fed either a high linolenic acid (perilla oil) or high eicosapentaenoic + docosahexaenoic acid (fish oil) diet (8%), and the fatty acid and molecular species composition of ethanolamine phosphoglycerides was determined. Gene expression pattern resulting from the feeding of n-3 fatty acids also was studied. Perilla oil feeding, in contrast to fish oil feeding, was not reflected in total fatty acid composition of ethanolamine phosphoglycerides. Levels of the alkenylacyl subclass of ethanolamine phosphoglycerides increased in response to feeding. Similarly, levels of diacyl phosphatidylethanolamine molecular species containing docosahexaenoic acid (18:0/22:6) were higher in perilla-fed or fish oil-fed rat brains whereas those in ethanolamine plasmalogens remained unchanged. Because plasmalogen levels in the brains of rats fed a n-3 fatty acid-enriched diet increased, it is plausible, however, that docosahexaenoic acid taken up from the food or formed from linolenic acid was deposited in this phospholipid subclass. Using cDNA microarrays, 55 genes were found to be overexpressed and 47 were suppressed relative to controls by both dietary regimens. The altered genes included those controlling synaptic plasticity, cytosceleton and membrane association, signal transduction, ion channel formation, energy metabolism, and regulatory proteins. This effect seems to be independent of the chain length of fatty acids, but the n-3 structure appears to be important. Because n-3 polyunsaturated fatty acids have been shown to play an important role in maintaining normal mental functions and docosahexaenoic acid-containing ethanolamine phosphoglyceride (18:0/22:6) molecular species accumulated in response to n-3 fatty acid feeding, a casual relationship between the two events can be surmised.