Depression and adipose polyunsaturated fatty acids in the survivors of the Seven Countries Study population of Crete

The purpose of the present study was to investigate the relation between adipose tissue polyunsaturated fatty acids, an index of long-term or habitual fatty acid dietary intake and depression. The sample consisted of 150 elderly males from the island of Crete. The subjects were survivors of the Greek Seven Countries Study group. The mean age was 84 years. The number of subjects with complete data on all variables studied was 63. Subjects were examined by the Preventive Medicine and Nutrition Clinic of the University of Crete. Depression was assessed through the use of the short form of the Geriatric Depression Scale (GDS-15). Depression correlated negatively with adipose tissue alpha-linolenic acid (C18:3n-3). Depressed subjects had significantly reduced (-10.5%) adipose tissue C18:3n-3 levels than non-depressed subjects. The observed negative relation between adipose tissue C18:3n-3 and depression, in the present study, appears to indicate increasing long-term dietary C18:3n-3 intakes with decreasing depression. This agrees with findings of other studies indicating an inverse relation between depression and consumption of fish and n-3 polyunsaturated fatty acids. This is the first literature report of a relation between adipose tissue C18:3n-3 and depression. Furthermore, this is the first report of a relation between adipose PUFA and depression in an elderly sample. Depression has been reported to be associated with elevated cytokines, such as, IL-1, IL-2, IL-6, INF-gamma and INF-alpha. Fish oil and omega-3 fatty acids, on the other hand, have been reported to inhibit cytokine production. The observed negative relation between adipose C18:3n-3 and depression, therefore, may stem from the inhibiting effect of C18:3n-3 or its long-chain metabolites on cytokine synthesis.     

Depression and adipose essential polyunsaturated fatty acids

The objective of the present study was to investigate the relation between adipose tissue polyunsaturated fatty acids, an index of long-term or habitual fatty acid dietary intake, and depression. The sample consisted of 247 healthy adults (146 males, 101 females) from the island of Crete. The number of subjects with complete data on all variables studied was 139. Subjects were examined at the Preventive Medicine and Nutrition Clinic of the University of Crete. Depression was assessed through the use of the Zung Self-rating Depression Scale. Mildly depressed subjects had significantly reduced (-34.6%) adipose tissue docosahexaenoic acid (DHA) levels than non-depressed subjects. Multiple linear regression analysis indicated that depression related negatively to adipose tissue DHA levels. In line with the findings of other studies, the observed negative relation between adipose tissue DHA and depression, in the present study, appears to indicate increasing long-term dietary DHA intakes with decreasing depression. This is the first literature report of a relation between adipose tissue DHA and depression. Depression has been reported to be associated with increased cytokine production, such as IL-1, IL-2, IL-6, INF-gamma and INF-alpha. On the other hand, fish oil and omega-3 fatty acids have been reported to inhibit cytokine synthesis. The observed negative relation between adipose DHA and depression, therefore, may stem from the inhibiting effect of DHA on cytokine synthesis.     

Omega-3 fatty acids in psychiatry

The brain is one of the organs with the highest level of lipids (fats). Brain lipids, formed of fatty acids, participate in the structure of membranes, for instance 50 % fatty acids are polyunsaturated in the gray matter, 1/3 are of the omega-3 family, and are thus of dietary origin. The omega-3 fatty acids (mainly alpha-linolenic acid, ALA) participated in one of the first experimental demonstration of the effect of dietary substances (nutrients) on the structure and function of the brain. Experiments were first of all carried out on ex vivo cultured brain cells, then on in vivo brain cells (neurons, astrocytes and oligodendrocytes) from animals fed ALA deficient diet, finally on physicochemical (membrane fluidity), biochemical, physiological, neurosensory (vision an auditory responses), and behavioural or learning parameters. These findings indicated that the nature of polyunsaturated fatty acids (in particular omega-3) present in formula milks for human infants determines to a certain extend the visual, neurological, and intellectual abilities. Thus, in view of these results and of the high polyunsaturated fatty acid content of the brain, it is normal to consider that they could be involved in psychiatric diseases and in the cognitive decline of ageing. Omega-3 fatty acids appear effective in the prevention of stress, however their role as regulator of mood is a matter for discussion. Indeed, they play a role in the prevention of some disorders including depression (especially post partum), as well as in dementia, particularly Alzheimer's disease. Their role in major depression and bipolar disorder (manic-depressive disease), only poorly documented, is not clearly demonstrated. The intervention of omega-3 in dyslexia, autism, and schizophrenia has been suggested, but it does not necessarily infer a nutritional problems. The respective importance of the vascular system (where the omega-3 are actually active) and the cerebral parenchyma itself, remain to be resolved. However, the insufficient supply of omega-3 fatty acids in today diet in occidental (less than 50 % of the recommended dietary intakes values for ALA) raises the problem of how to correct inadequate dietary habits, by prescribing mainly rapeseed (canola) and walnut oils on the one hand, fatty fish (wild, or farmed, but the nature of fatty acids present in fish flesh is the direct consequence of the nature of fats with which they have been fed), and eggs from laying hens fed omega-3 fatty acids.     

Engineering oilseeds to produce nutritional fatty acids

There is a growing body of evidence suggesting that regular consumption of foods rich in omega-3 long chain polyunsaturated fatty acids has multiple positive health benefits. The fats and oils from marine fish contain high contents of these beneficial fatty acids but increased consumer demand has also increased strain on the ability of the world's fisheries to meet demand from wild capture. Many consumers are choosing fish oil supplements or are eating foods that have been complemented with fish oils instead of consuming fish directly. However, removing undesirable odors, flavors and contaminants is expensive. In contrast, oils derived from land plants such as soybean are inexpensive and contaminant free. Recent strides in plant molecular biology now allow the engineering of oilseeds for the production of novel fats and oils, including those synthesized by complex, multigene biosynthetic pathways such as the omega-3 long chain polyunsaturated fatty acids. Given the potential benefits to the environment with regards to overfishing and the health prospects of increased consumption of these healthy fatty acids, producing these fatty acids in oilseeds is a desirable and worthy goal. In this review, we will describe the recent advances in this field along with some of the technical hurdles encountered thus far.     

Enhancement of activity and selectivity of Candida rugosa lipase and Candida antarctica lipase A by bioimprinting and/or immobilization for application in the selective ethanolysis of fish oil

Candida rugosa lipase (CRL) and Candida antarctica lipase A (CALA) with improved activity and selectivity were prepared for use in organic solvent media. CRL bioimprinted with fatty acids exhibited eightfold enhanced transesterification activity in hexane. Combination of bioimprinting and coating with lecithin or with immobilization did not improve the activity further. CALA was immobilized with and without bioimprinting, none of which improved the activity. All modified lipases were tested for selective ethanolysis of fish oil to concentrate omega-3 polyunsaturated fatty acids (PUFA). None of the preparations, except the immobilized ones catalysed ethanolysis. Immobilized CRL-catalyzed ethanolysis giving 27% (v/v) ethyl esters (EE) in 48 h, of which 43 mol% was oleic acid but no PUFA was detected in the EE fraction. Fatty acid selectivity of CALA was significantly improved by immobilization combined with bioimprinting, resulting in 5.5-fold lower omega-3 PUFA in EE.     

No clear evidence of an association between plasma concentrations of n-3 long-chain polyunsaturated fatty acids and depressed mood in a non-clinical population

Previous research suggests that low n-3 long-chain polyunsaturated fatty acid (n-3PUFA) status is associated with higher levels of depression in clinical populations. This analysis aimed to investigate the relationship between depressed mood and n-3PUFA status in a non-clinical population. The analysis was conducted on data collected as part of a large randomized controlled trial investigating the impact of n-3PUFA supplementation on depressed mood in a community-based population. On entry into the trial, data on depressed mood were collected using the Depression, Anxiety and Stress Scales (DASS) and the Beck Depression Inventory (BDI). Plasma concentrations of various n-3PUFAs and n-6 long-chain polyunsaturated fatty acids (n-6PUFAs) were obtained from fasting venous blood samples, and various demographics were also measured. Using regression, there was no evidence of an association between either measure of depressed mood and any of the measures of n-3PUFA status or of n-6PUFA:n-3PUFA ratios. Clear associations were also not found when demographic factors were included in the analyses. These findings suggest that n-3PUFAs may not have a role in the aetiology of minor depression. This is also consistent with the results of other studies that have not demonstrated an association between depressed mood and n-3PUFA status in non-clinical populations and epidemiological studies that have not demonstrated an association between depressed mood and n-3PUFA intake in these populations.     

Omega-3 fatty acids and neuropsychiatric disorders

Epidemiological evidence suggests that dietary consumption of the long chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), commonly found in fish or fish oil, may modify the risk for certain neuropsychiatric disorders. As evidence, decreased blood levels of omega-3 fatty acids have been associated with several neuropsychiatric conditions, including Attention Deficit (Hyperactivity) Disorder, Alzheimer's Disease, Schizophrenia and Depression. Supplementation studies, using individual or combination omega-3 fatty acids, suggest the possibility for decreased symptoms associated with some of these conditions. Thus far, however, the benefits of supplementation, in terms of decreasing disease risk and/or aiding in symptom management, are not clear and more research is needed. The reasons for blood fatty acid alterations in these disorders are not known, nor are the potential mechanisms by which omega-3 fatty acids may function in normal neuronal activity and neuropsychiatric disease prevention and/or treatment. It is clear, however, that DHA is the predominant n-3 fatty acid found in the brain and that EPA plays an important role as an anti-inflammatory precursor. Both DHA and EPA can be linked with many aspects of neural function, including neurotransmission, membrane fluidity, ion channel and enzyme regulation and gene expression. This review summarizes the knowledge in terms of dietary omega-3 fatty acid intake and metabolism, as well as evidence pointing to potential mechanisms of omega-3 fatty acids in normal brain functioning, development of neuropsychiatric disorders and efficacy of omega-3 fatty acid supplementation in terms of symptom management.     

Effect of saturated, omega-3 and omega-6 polyunsaturated fatty acids on myocardial infarction

Dietary fatty acids have cholesterol lowering, antiatherogenic, and antiarrhythmic properties that decrease the risk of myocardial infarction (MI). This study was designed to study the effects of various oils rich in either polyunsaturated (omega-3 or omega-6) fatty acids (PUFA) or saturated fatty acids (SFA) on the severity of experimentally induced MI. Male albino Sprague-Dawley rats (100-150 g; n = 20) were fed diets enriched with fish oil (omega-3 PUFA), peanut oil (omega-6 PUFA), or coconut oil (SFA) for 60 days. Experimental MI was induced with isoproterenol. Mortality rates; serum enzymes aspartate amino transferase; alanine amino transferase; creatine phosphokinase (CPK); lipid profiles in serum, myocardium, and aorta; peroxide levels in heart and aorta; activities of catalase and superoxide dismutase; and levels of glutathione were measured. The results demonstrated that mortality rate, CPK levels, myocardial lipid peroxides, and glutathione levels were decreased in the omega-3 PUFA treated group. Maximum increase in parameters indicative of myocardial damage was seen in the coconut oil group. These findings suggest that dietary omega-3 PUFA offers maximum protection in experimentally induced MI in comparison to omega-6 PUFA and SFA enriched diets. SFA was found to have the least protective effect.     

Omega-3 Fatty Acids for Depression in Multiple Sclerosis: A Randomized Pilot Study

Multiple sclerosis is the most common chronic disabling disease in the central nervous system in young to middle aged adults. Depression is common in multiple sclerosis (MS) affecting between 50–60% of patients. Pilot studies in unipolar depression report an improvement in depression when omega-3 fatty acids are given with antidepressants. The objective of this study was to investigate whether omega-3 fatty acid supplementation, as an augmentation therapy, improves treatment-resistant major depressive disorder (MDD) in people with MS. We performed a randomized, double-blind, placebo-controlled pilot study of omega-3 fatty acids at six grams per day over three months. The primary outcome was a 50% or greater improvement on the Montgomery-Asberg Depression Rating Scale (MADRS). Thirty-nine participants were randomized and thirty-one completed the 3-month intervention. Improvement on MADRS between groups was not significantly different at the 3-month end point with 47.4% in the omega-3 fatty acid group and 45.5% in the placebo group showing 50% or greater improvement (p = 0.30). Omega-3 fatty acids as an augmentation therapy for treatment-resistant depression in MS was not significantly different than placebo in this pilot trial. Omega-3 fatty acid supplementation at the dose given was well-tolerated over 3 months.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00122954","term_id":"NCT00122954"}}NCT00122954     

Preferential enrichment of liver phospholipids in docosahexaenoate relative to eicosapentaenoate in omega-3-depleted rats injected with a medium-chain triglyceride: fish oil emulsion

The bolus intravenous injection of a novel medium-chain triglyceride:fish oil (FO) emulsion was recently proposed as a tool to provoke a rapid enrichment of cell phospholipids in long-chain polyunsaturated omega-3 fatty acids. In the present study, the enrichment of liver phospholipids and triglycerides in C20:5omega-3, C22:5omega-3 and C22:6omega-3 was assessed 60min after the intravenous administration of FO (1.0ml) to second-generation omega-3-depleted rats. When compared to uninjected rats, or animals injected with a control omega-3 fatty acid-poor medium-chain triglyceride:olive oil (OO) emulsion, the enrichment of liver phospholipids, and to a lesser extent liver triglycerides, attributable to the injection of the FO emulsion was more pronounced for C22:6omega-3 than C20:5omega-3, despite the presence of equal amounts of these two omega-3 fatty acids in the injected diglycerides and triglycerides. The possible determinants and potential beneficial effects of such a difference are briefly discussed.     

Inhibition of leukocyte-endothelial interactions by oxidized omega-3 fatty acids: a novel mechanism for the anti-inflammatory effects of omega-3 fatty acids in fish oil

Omega-3 fatty acids which are abundant in fish oil improve the prognosis of several chronic inflammatory diseases that are characterized by leukocyte-mediated tissue injury. The omega-3 fatty acids, such as eicosapentaenoic acid (EPA), are highly polyunsaturated and readily undergo oxidation. Our data suggest that the beneficial effects of fish oil may be due to the oxidative modification of omega-3 fatty acids. The oxidized products inhibit leukocyte adhesion receptor expression and leukocyte-endothelial interactions. Oxidized EPA is a potent inhibitor of leukocyte interactions with the endothelium compared to native EPA, both in vitro and in an in vivo context of inflammation. The effects of oxidized EPA are mediated through activation of PPARalpha and subsequent inhibition of NF-kappaB, leading to the down-regulation of leukocyte adhesion receptor expression required for leukocyte-endothelial interactions. We propose that oxidation of EPA and its activation of PPARalpha and subsequent inhibition of NF-kappaB is the underlying mechanism for the beneficial effects of fish oil.     

Effects of dietary polyunsaturated fatty acid on platelet aggregation in rats

In the present study, we changed the fatty acid profile in blood and platelet membranes by dietary manipulation, and examined the effect on platelet aggregation in rats. Fifty-five rats were divided into five groups and fed for 56 days with 1% cholesterol and different types of fatty acid-rich diets: basal, lard, lard + fish oil, soybean oil, and soybean oil + fish oil. a decrease in serum arachidonic acid (20:4, omega-6, AA) and an increase in serum eicosapentaenoic acid (20:5, omega-3, EPA) were found in all experimental dietary groups fed with refined fish oil. Similar changes in the polyunsaturated fatty acids were also found in the platelet membrane phospholipids. Platelet aggregation, quantitated by the slope and height of the aggregation curve induced by different concentrations of ADP in a platelet aggregometer, was inhibited in all groups fed with refined fish oil. This inhibition of platelet aggregation may be related to an increase in the ratio of EPA and AA in the platelet membrane phospholipids after dietary manipulation. The differences in the platelet aggregation and thromboxane B2 (TXB2) concentration between the lard and the lard + fish oil groups were more profound than that between the soybean oil and the soybean oil + fish oil group. However, the malondialdehyde (MDA) concentration revealed no significant differences between the five groups.     

The synthesis and accumulation of stearidonic acid in transgenic plants: a novel source of 'heart-healthy' omega-3 fatty acids

Dietary omega-3 polyunsaturated fatty acids have a proven role in reducing the risk of cardiovascular disease and precursor disease states such as metabolic syndrome. Although most studies have focussed on the predominant omega-3 fatty acids found in fish oils (eicosapentaenoic acid and docosahexaenoic acid), recent evidence suggests similar health benefits from their common precursor, stearidonic acid. Stearidonic acid is a Δ6-unsaturated C18 omega-3 fatty acid present in a few plant species (mainly the Boraginaceae and Primulaceae ) reflecting the general absence of Δ6-desaturation from higher plants. Using a Δ6-desaturase from Primula vialii , we generated transgenic Arabidopsis and linseed lines accumulating stearidonic acid in their seed lipids. Significantly, the P. vialii Δ6-desaturase specifically only utilises α-linolenic acid as a substrate, resulting in the accumulation of stearidonic acid but not omega-6 γ-linolenic acid. Detailed lipid analysis revealed the accumulation of stearidonic acid in neutral lipids such as triacylglycerol but an absence from the acyl-CoA pool. In the case of linseed, the achieved levels of stearidonic acid (13.4% of triacylglycerols) are very similar to those found in the sole natural commercial plant source ( Echium spp.) or transgenic soybean oil. However, both those latter oils contain γ-linolenic acid, which is not normally present in fish oils and considered undesirable for heart-healthy applications. By contrast, the stearidonic acid-enriched linseed oil is essentially devoid of this fatty acid. Moreover, the overall omega-3/omega-6 ratio for this modified linseed oil is also significantly higher. Thus, this nutritionally enhanced linseed oil may have superior health-beneficial properties.     

Stimulation of anaphylaxis in the mouse footpad by dietary fish oil fatty acids

The effect of fish oil-derived omega-3 (omega-3) fatty acids on anaphylaxis, Arthus and delayed type hypersensitivity reactions in mice has been investigated. Mice on a normal chow diet were fed eicosapentaenoic acid and docosahexaenoic acid at a dose of 500 and 333 mg/kg/day, respectively, by a gastric tube over a period of 61 days. Control groups were given water, safflower oil or oleic acid. Anaphylactic and Arthus type reactions were induced in the mouse footpad using bovine serum albumin as an antigen. Carrageenin was utilized to produce a delayed type hypersensitivity reaction. The animals fed omega-3 fatty acids induced a more anaphylactic foodpad reaction. There was no significant effect of the diet on Arthus and delayed type hypersensitivity responses. There was no effect of the fish oil-supplemented diet on production of antibodies to bovine serum albumin. Synthesis of prostaglandin E2 by peritoneal macrophages was significantly inhibited in the animals fed omega-3 fatty acid-enriched fish oil, while leukotriene B4 production was not affected. These results suggest that a diet enriched in omega-3 fatty acids modulates production of arachidonic acid metabolites and this may influence anaphylaxis, but not Arthus and cellular mediated hypersensitivity responses.     

Biomechanical bone strength and bone mass in young male and female rats fed a fish oil diet

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.     

Enzyme catalysed production of vegetable oils containing omega-3 polyunsaturated fatty acid

Summary The application of enzymatic interesterification for production of vegetable oils containing omega-3 polyunsaturated fatty acids was investigated. Six veteable oils were used as substrates, together with omega-3 polyunsaturated fatty acid, and reactions were catalysed by immobilized Mucor miehei lipase in organic solvent. The degree of incorporation of eicosapentaenoic acid and docosahexaenoic acid into corn oil, sunflower oil, peanut oil, olive oil and soybean oil were 17.71, 17.59, 16.79, 14.89, 13.91 and 10.48%, respectively, after a 12 h incubation period.     

Inhibition of leukocyte–endothelial interactions by oxidized omega-3 fatty acids: a novel mechanism for the anti-inflammatory effects of omega-3 fatty acids in fish oil

Abstract

Omega-3 fatty acids which are abundant in fish oil improve the prognosis of several chronic inflammatory diseases that are characterized by leukocyte-mediated tissue injury. The omega-3 fatty acids, such as eicosapentaenoic acid (EPA), are highly polyunsaturated and readily undergo oxidation. Our data suggest that the beneficial effects of fish oil may be due to the oxidative modification of omega-3 fatty acids. The oxidized products inhibit leukocyte adhesion receptor expression and leukocyte-endothelial interactions. Oxidized EPA is a potent inhibitor of leukocyte interactions with the endothelium compared to native EPA, both in vitro and in an in vivo context of inflammation. The effects of oxidized EPA are mediated through activation of PPARα and subsequent inhibition of NF-κB, leading to the down-regulation of leukocyte adhesion receptor expression required for leukocyte-endothelial interactions. We propose that oxidation of EPA and its activation of PPARα and subsequent inhibition of NF-κB is the underlying mechanism for the beneficial effects of fish oil.     

Effect of dietary fish oil (active EPA-30) on liver phospholipids in young and aged rats.

We explored the uses of fish oil (active EPA-30) as a source of eicosapentaenate (EPA; 20:5 n-3), to young and old rats. We treated three subgroups of rats each comprising 20 young or old rats, respectively. The first group was kept on the basal ration (lab-pellet) as control diet, the second group was fed semi-purified diets contained 5% pig-fat (n-3 fatty acids deficient diet). The third group was fed a modified diet in which 50% of pig-fat was replaced by active EPA-30. Livers of young rats fed pig-fat had a drastic decrease in the amount of phosphatidylethanolamine (PE) and omega-3 polyunsaturated fatty acids (EPA, 20:5 n-3 and docosahexaenoic, DHA, 22:6 n-3) and compensatory increase of phosphatidylcholine, saturated fatty acids and n-6 polyunsaturated fatty acids in the liver phospholipids. In contrast, the liver of young rats fed active EPA-30 had large amounts of PE and concomitant enrichment in polyunsaturated fatty acids. The liver of old rats, fed on active EPA-30 supplemented diet had lower amounts of PE and there were no significant changes in the phospholipid fatty acid composition.     

Modulation of enzymatic activities by n-3 polyunsaturated fatty acids to support cardiovascular health

Epidemiological evidence from Greenland Eskimos and Japanese fishing villages suggests that eating fish oil and marine animals can prevent coronary heart disease. Dietary studies from various laboratories have similarly indicated that regular fish oil intake affects several humoral and cellular factors involved in atherogenesis and may prevent atherosclerosis, arrhythmia, thrombosis, cardiac hypertrophy and sudden cardiac death. The beneficial effects of fish oil are attributed to their n-3 polyunsaturated fatty acid (PUFA; also known as omega-3 fatty acids) content, particularly eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Dietary supplementation of DHA and EPA influences the fatty acid composition of plasma phospholipids that, in turn, may affect cardiac cell functions in vivo. Recent studies have demonstrated that long-chain omega-3 fatty acids may exert beneficial effects by affecting a wide variety of cellular signaling mechanisms. Pathways involved in calcium homeostasis in the heart may be of particular importance. L-type calcium channels, the Na+-Ca2+ exchanger and mobilization of calcium from intracellular stores are the most obvious key signaling pathways affecting the cardiovascular system; however, recent studies now suggest that other signaling pathways involving activation of phospholipases, synthesis of eicosanoids, regulation of receptor-associated enzymes and protein kinases also play very important roles in mediating n-3 PUFA effects on cardiovascular health. This review is therefore focused on the molecular targets and signaling pathways that are regulated by n-3 PUFAs in relation to their cardioprotective effects.     

Effects of dietary fish oil on plasma high density lipoprotein. Electron spin resonance and fluorescence polarization studies of lipid ordering and dynamics.

Dietary fish oils are implicated in reducing the incidence of coronary heart disease, perhaps by altering the properties of plasma lipoproteins. The hypothesis that omega-3 polyunsaturated fatty acids (PUFA) in fish oils produce changes in lipid ordering and dynamics within high density lipoprotein (HDL), thereby potentially modifying cholesterol transport, is investigated here. Rabbits were fed a diet supplemented with either 10% (by weight) menhaden oil (MO), a fish oil rich in omega-3 PUFAs, or hydrogenated cottonseed oil for a period of 12 weeks. HDL was isolated by sequential flotation ultracentrifugation from plasma drawn every 2 weeks. Gas chromatography confirmed that the predominant omega-3 PUFAs of fish oils, eicosapentaenoic 20:5 and docosahexaenoic 22:6 acids, were only incorporated into the triglyceride, phospholipid, and cholesteryl ester constituents of lipoproteins from rabbits on the MO diet. ESR of 5- and 16-doxyl stearic acids demonstrates that molecular order and dynamics within the outer monolayer of HDL is virtually unaffected. In contrast, ESR of cholesteryl 12-doxyl stearate indicates order is less within the inner apolar core of the lipoprotein for the MO diet than for the hydrogenated cottonseed oil diet. Fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene supports this finding. The greater disorder detected within HDL from rabbits fed fish oil may result in an enhancement of cholesterol exchange between lipoproteins and between lipoproteins and cells, which may have anti-atherogenic ramifications.