Fish oil supplementation of maternal rats on an n-3 fatty acid-deficient diet prevents depletion of maternal brain regional docosahexaenoic acid levels and has a postpartum anxiolytic effect

Docosahexaenoic acid (DHA) and arachidonic acid (AA) are the major polyunsaturated fatty acids (PUFA) in the neuronal membrane. Most DHA and AA accumulation in the brain occurs during the perinatal period via placenta and milk. This study examined whether maternal brain levels of DHA and AA are depleted during pregnancy and lactation due to meeting the high demand of the developing nervous system in the offspring and evaluated the effects of the reproductive cycle on serotonin metabolism and of fish oil (FO) on postpartum anxiety. Pregnant rats were fed during pregnancy and lactation with a sunflower oil-based n-3 PUFA-deficient diet without or with FO supplementation, which provided 0.37% of the energy source as n-3 PUFA, and the age-matched virgin rats were fed the same diets for 41 days. In both sets of postpartum rats, decreased DHA levels compared to those in virgin females were seen in the hypothalamus, hippocampus, frontal cortex, cerebellum, olfactory bulb and retina, while AA depletion was seen only in the hypothalamus, hippocampus and frontal cortex. Serotonin levels were decreased and turnover increased in the brainstem and frontal cortex in postpartum rats compared to virgin rats. FO supplementation during pregnancy and lactation prevented the decrease in maternal brain regional DHA levels, inhibited monoamine oxidase-A activity in the brainstem and decreased anxiety-like behavior. We propose that the reproductive cycle depletes maternal brain DHA levels and modulates maternal brain serotonin metabolism to cause postpartum anxiety and suggest that FO supplementation may be beneficial for postpartum anxiety in women on an n-3 PUFA-deficient diet.     

Enhanced production of carotenoids using a Thraustochytrid microalgal strain containing high levels of docosahexaenoic acid-rich oil

Bioprocess and Biosystems Engineering - Results to date suggest that microalgal Thraustochytrids family strains can be used to produce high-functional omega-3 rich oil (~ 30–70% of dry...     

Recycling of docosahexaenoic acid in rat retinas during n-3 fatty acid deficiency.

About 50% of the fatty acids in retinal rod outer segments is docosahexaenoic acid [22:6(n-3)], a member of the linolenic acid [18:3(n-3)] family of essential fatty acids. Dietary deprivation of n-3 fatty acids leads to only modest changes in 22:6(n-3) levels in the retina. We investigated the mechanism(s) by which the retina conserves 22:6(n-3) during n-3 fatty acid deficiency. Weanling rats were fed diets containing 10% (wt/wt) hydrogenated coconut oil (no n-3 or n-6 fatty acids), linseed oil (high n-3, low n-6), or safflower oil (high n-6, less than 0.1% n-3) for 15 weeks. The turnover of phospholipid molecular species and the turnover and recycling of 22:6(n-3) in phospholipids of the rod outer segment membranes were examined after the intravitreal injection of [2-3H]glycerol and [4,5-3H]22:6(n-3), respectively. Animals were killed on selected days, and rod outer segment membranes, liver, and plasma were taken for lipid analyses. The half-lives (days) of individual phospholipid molecular species and total phospholipid 22:6(n-3) were calculated from the slopes of the regression lines of log specific activity versus time. There were no differences in the turnover rates of phospholipid molecular species among the three dietary groups, as determined by the disappearance of labeled glycerol. Thus, 22:6(n-3) is not conserved through a reduction in phospholipid turnover in rod outer segments. However, the half-life of [4,5-3H]22:6(n-3) in the linseed oil group (19 days) was significantly less than in the coconut oil (54 days) and safflower oil (not measurable) groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Divergent effects of eicosapentaenoic and docosahexaenoic acid ethyl esters, and fish oil on hepatic fatty acid oxidation in the rat

The physiological activity of fish oil, and ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) affecting hepatic fatty acid oxidation was compared in rats. Five groups of rats were fed various experimental diets for 15 days. A group fed a diet containing 9.4% palm oil almost devoid of n-3 fatty acids served as a control. The test diets contained 4% n-3 fatty acids mainly as EPA and DHA in the form of triacylglycerol (9.4% fish oil) or ethyl esters (diets containing 4% EPA ethyl ester, 4% DHA ethyl ester, and 1% EPA plus 3% DHA ethyl esters). The lipid content of diets containing EPA and DHA ethyl esters was adjusted to 9.4% by adding palm oil. The fish oil diet and ethyl ester diets, compared to the control diet containing 9.4% palm oil, increased activity and mRNA levels of hepatic mitochondrial and peroxisomal fatty acid oxidation enzymes, though not 3-hydroxyacyl-CoA dehydrogenase activity. The extent of the increase was, however, much greater with the fish oil than with EPA and DHA ethyl esters. EPA and DHA ethyl esters, compared to the control diet, increased 3-hydroxyacyl-CoA dehydrogenase activity, but fish oil strongly reduced it. It is apparent that EPA and DHA in the form of ethyl esters cannot mimic the physiological activity of fish oil at least in affecting hepatic fatty acid oxidation in rat.     

Effect of omega-3 fatty acids, docosahexaenoic and eicosapentaenoic, on norepinephrine-induced contractions.

The relaxant responses of the rat thoracic aorta to omega-3 fatty acids, docosahexaenoic and eicosapentaenoic, on norepinephrine- and potassium-induced contractions were investigated. Relaxation was enhanced in vessels contracted with norepinephrine. Docosahexaenoic acid at concentrations as low as 1, 3, and 10 microM evoked significant relaxant responses (15, 23, 30%) in norepinephrine-contracted vessels as compared with responses (5, 9, 12%) in potassium-contracted vessels. Results for eicosapentaenoic acid under similar conditions were 3, 8, and 19% in norepinephrine-contracted vessels and 3, 3, and 8% in potassium-contracted vessels. Pretreatment with eicosapentaenoic (10 microM) or docosahexaenoic acids (1-10 microM) decreased the contractile response to physiologic concentrations of norepinephrine. In the presence of calcium-free medium, the omega-3 fatty acids (1-30 microM) significantly abolished sustained norepinephrine contractions but did not reduce the phasic contractions when incubated prior to norepinephrine contraction. Comparatively, the effects of docosahexaenoic acid were greater than eicosapentaenoic acid. These findings suggest that the relaxant effects of the omega-3 fatty acids are specific to the mode of contraction, i.e., alpha-adrenoceptor stimuli. This effect may be related to intracellular calcium mechanisms, since both fatty acids reversed norepinephrine-induced sustained contractions in the absence of extracellular calcium.     

Dietary n-6 polyunsaturated fatty acid deprivation increases docosahexaenoic acid metabolism in rat brain

Dietary n-6 polyunsaturated fatty acid (PUFA) deprivation in rodents reduces brain arachidonic acid (20:4n-6) concentration and 20:4n-6-preferring cytosolic phospholipase A(2) (cPLA(2) -IVA) and cyclooxygenase (COX)-2 expression, while increasing brain docosahexaenoic acid (DHA, 22:6n-3) concentration and DHA-selective calcium-independent phospholipase A(2) (iPLA(2) )-VIA expression. We hypothesized that these changes are accompanied by up-regulated brain DHA metabolic rates. Using a fatty acid model, brain DHA concentrations and kinetics were measured in unanesthetized male rats fed, for 15 weeks post-weaning, an n-6 PUFA 'adequate' (31.4 wt% linoleic acid) or 'deficient' (2.7 wt% linoleic acid) diet, each lacking 20:4n-6 and DHA. [1-(14) C]DHA was infused intravenously, arterial blood was sampled, and the brain was microwaved at 5 min and analyzed. Rats fed the n-6 PUFA deficient compared with adequate diet had significantly reduced n-6 PUFA concentrations in brain phospholipids but increased eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acid n-3 (DPAn-3, 22:5n-3), and DHA (by 9.4%) concentrations, particularly in ethanolamine glycerophospholipid (EtnGpl). Incorporation rates of unesterified DHA from plasma, which represent DHA metabolic loss from brain, were increased 45% in brain phospholipids, as was DHA turnover. Increased DHA metabolism following dietary n-6 PUFA deprivation may increase brain concentrations of antiinflammatory DHA metabolites, which with a reduced brain n-6 PUFA content, likely promotes neuroprotection and alters neurotransmission.     

Peroxisomal retroconversion of docosahexaenoic acid (22:6(n-3)) to eicosapentaenoic acid (20:5(n-3)) studied in isolated rat liver cells.

Retroconversion of docosahexaenoic acid (DHA, 22:6(n-3)) to eicosapentaenoic acid (EPA, 20:5(n-3)) was studied in isolated rat liver cells. 20% of the substrate was retroconverted to EPA in control cells by one cycle of beta-oxidation probably with delta 4 enoyl CoA reductase and delta 3, delta 2 enoyl CoA isomerase as auxiliary enzymes. This conversion was not stimulated by (-)-carnitine and was not inhibited by the addition of (+)-decanoylcarnitine. In hepatocytes from fasted rats little EPA was formed from DHA. These results strongly suggest that the retroconversion of DHA to EPA is a peroxisomal function. Retroconverted EPA, produced from DHA was rapidly incorporated in triacylglycerol, the phosphatidylcholine and phosphatidyletanolamine fractions. During longer incubation time EPA was partly removed from the phospholipid fractions, chain-elongated to 22:5(n-3) and incorporated in the triacylglycerol fraction.     

Fatty acid alterations and n-3 fatty acid supplementation in cystic fibrosis

Specific fatty acid alterations have been described in the blood and tissues of cystic fibrosis (CF) patients. The two most consistent alterations include decreased levels of linoleic acid (LA) and decreased levels of docosahexaenoic acid (DHA). Increased arachidonic acid (AA) release from membrane phospholipids, as well as changes in levels of AA and other monounsaturated and polyunsaturated fatty acids (PUFAs) have also been described in CF. Although mechanisms of fatty acid alterations have not yet been determined, these alterations may have an important role in the progression of the CF disease. There have been several clinical trials in which CF patients were supplemented with n-3 fatty acids. Most trials resulted in an increase in the levels of the supplemental fatty acids in the blood of CF patients in the absence of significant clinical improvement. It is recommended that future trials include a larger population of CF patients and measure multiple clinical outcomes.     

Dietary supplementation with docosahexaenoic acid, but not eicosapentaenoic acid, dramatically alters cardiac mitochondrial phospholipid fatty acid composition and prevents permeability transition

Treatment with the ω-3 polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) exerts cardioprotective effects, and suppresses Ca²⁺-induced opening of the mitochondrial permeability transition pore (MPTP). These effects are associated with increased DHA and EPA, and lower arachidonic acid (ARA) in cardiac phospholipids. While clinical studies suggest the triglyceride lowering effects of DHA and EPA are equivalent, little is known about the independent effects of DHA and EPA on mitochondria function. We compared the effects of dietary supplementation with the ω-3 PUFAs DHA and EPA on cardiac mitochondrial phospholipid fatty acid composition and Ca²⁺-induced MPTP opening. Rats were fed a standard lab diet with either normal low levels of ω-3 PUFA, or DHA or EPA at 2.5% of energy intake for 8 weeks, and cardiac mitochondria were isolated and analyzed for Ca²⁺-induced MPTP opening and phospholipid fatty acyl composition. DHA supplementation increased both DHA and EPA and decreased ARA in mitochondrial phospholipid, and significantly delayed MPTP opening as assessed by increased Ca²⁺ retention capacity and decreased Ca²⁺-induced mitochondria swelling. EPA supplementation increased EPA in mitochondrial phospholipids, but did not affect DHA, only modestly lowered ARA, and did not affect MPTP opening. In summary, dietary supplementation with DHA but not EPA, profoundly altered mitochondrial phospholipid fatty acid composition and delayed Ca²⁺-induced MPTP opening.     

Trans n-3 eicosapentaenoic and docosahexaenoic acid isomers exhibit different inhibitory effects on arachidonic acid metabolism in human platelets compared to the respective cis fatty acids

N-3 trans geometrical isomers of 20:5 n-3 and 22:6 n-3 were isolated from rats fed heated linseed oil. The ability of these acids to inhibit 20:4 n-6 metabolism by human platelets was examined. The concentrations required to inhibit 50% of platelet aggregation (IC50) induced by 2.5 microM 20:4 n-6 were higher for the 20:5 delta 17t isomer compared to all cis 20:5 n-3; means 29.2 and 7.6 microM, respectively (P less than 0.05). There were no significant differences in IC50 between 22:6 delta 19t and all cis 22:6 n-3; means 4.3 and 5.6 microM, respectively (P greater than 0.05). Inhibition of action of cyclooxygenase on 20:4 n-6 was similar for 20:5 delta 17t and 20:5 n-3 when examined at their IC50s, but comparison at equal concentrations indicated that 20:5 n-3 was a significantly better inhibitor (P less than 0.05). The ability to inhibit platelet aggregation was paralleled by cyclooxygenase inhibition as determined by thromboxane B2 and 12-hydroxyheptadecatrienoic acid formation. 22:6 delta 19t appeared to inhibit cyclooxygenase more completely than 22:6 n-3, examined at their IC50s or at similar concentrations (P less than 0.05). Isomers of 20:5 n-3 and 22:6 n-3 having an n-3 cis or trans bond appear to have similar modes of action, although levels required for effectiveness are different for the C20 acids.     

Assessment of blood measures of n-3 polyunsaturated fatty acids with acute fish oil supplementation and washout in men and women

Changes in n-3 highly unsaturated fatty acids (HUFA, ≥20 carbons and ≥3 carbon–carbon double bonds) at baseline, during fish oil supplementation (4 weeks) and during washout (8 weeks) were compared in venous plasma, erythrocytes, whole blood and fingertip prick blood (weeks 0, 4, 8 and 12) with additional weekly fingertip prick samples. Correlations between the various blood fractions were slightly stronger when n-3 HUFA status was expressed as the percentage of n-3 HUFA in total HUFA as compared with the sum of EPA and DHA. Increases and decreases in n-3 HUFA were more dramatic in plasma, and EPA responded rapidly (within 1 week) with fish oil supplementation and cessation. Sex differences in the proportions of n-3 HUFA in blood were also apparent at baseline with females (n=7) having a tendency for higher docosahexaenoic acid (DHA, 22:6n-3) relative to eicosapentaenoic acid (EPA, 20:5n-3) and n-3 docosapentaenoic acid (DPAn-3, 22:5n-3) as compared with males (n=9). Further n-3 biomarker research in larger populations is required.     

Half-lives of docosahexaenoic acid in rat brain phospholipids are prolonged by 15 weeks of nutritional deprivation of n-3 polyunsaturated fatty acids

Male rat pups (21 days old) were placed on a diet deficient in n-3 polyunsaturated fatty acids (PUFAs) or on an n-3 PUFA adequate diet containing alpha-linolenic acid (alpha-LNA; 18 : 3n-3). After 15 weeks on a diet, [4,5-3H]docosahexaenoic acid (DHA; 22 : 6n-3) was injected into the right lateral cerebral ventricle, and the rats were killed at fixed times over a period of 60 days. Compared with the adequate diet, 15 weeks of n-3 PUFA deprivation reduced plasma DHA by 89% and brain DHA by 37%; these DHA concentrations did not change thereafter. In the n-3 PUFA adequate rats, DHA loss half-lives, calculated by plotting log10 (DHA radioactivity) against time after tracer injection, equaled 33 days in total brain phospholipid, 23 days in phosphatidylcholine, 32 days in phosphatidylethanolamine, 24 days in phosphatidylinositol and 58 days in phosphatidylserine; all had a decay slope significantly greater than 0 (p < 0.05). In the n-3 PUFA deprived rats, these half-lives were prolonged twofold or greater, and calculated rates of DHA loss from brain, Jout, were reduced. Mechanisms must exist in the adult rat brain to minimize DHA metabolic loss, and to do so even more effectively in the face of reduced n-3 PUFA availability for only 15 weeks.     

Global survey of the omega-3 fatty acids,docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults

Studies reporting blood levels of the omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were systematically identified in order to create a global map identifying countries and regions with different blood levels. Included studies were those of healthy adults, published in 1980 or later. A total of 298 studies met all inclusion criteria. Studies reported fatty acids in various blood fractions including plasma total lipids (33%), plasma phospholipid (32%), erythrocytes (32%) and whole blood (3.0%). Fatty acid data from each blood fraction were converted to relative weight percentages (wt.%) and then assigned to one of four discrete ranges (high, moderate, low, very low) corresponding to wt.% EPA + DHA in erythrocyte equivalents. Regions with high EPA + DHA blood levels (> 8%) included the Sea of Japan, Scandinavia, and areas with indigenous populations or populations not fully adapted to Westernized food habits. Very low blood levels (≤ 4%) were observed in North America, Central and South America, Europe, the Middle East, Southeast Asia, and Africa. The present review reveals considerable variability in blood levels of EPA + DHA and the very low to low range of blood EPA + DHA for most of the world may increase global risk for chronic disease.     

Reduction of hyperlipidemia in the LA/N-corpulent rat by dietary fish oil containing n-3 fatty acids

The LA/N rat, when homozygous for the corpulent gene (cp/cp), is obese, hyperphageous, hyperinsulinemic, hypertriglyceridemic and prone to the development of vascular and myocardial lesions. The hypertriglyceridemia, which in 3-month-old cp/cp males is 282 +/- 42 mg/dl and in females, 512 +/- 83 mg/dl, results from the presence of a large triacylglycerol-rich VLDL. The moderate hypercholesterolemia in these animals is largely due to markedly elevated HDL levels, which reach 172 +/- 21 mg total lipid/dl in males and 154 +/- 22 mg total lipid/dl in females. The LA/N-cp rat is thus an interesting animal model of endogenous hypertriglyceridemia in which to examine the hypolipidemic effects of pharmacological agents and also dietary oil supplements containing the n-3 fatty acids. In this study, 1-month-old male and female cp/cp rats were fed a normal low fat laboratory chow supplemented with either 10% olive oil or 10% redfish (Sebastes marinus) oil ad libitum for a period of 2 months. The redfish oil contained 4.9 +/- 0.1% of its total fatty acids as eicosapentaenoic (20:5(n-3)) and 2.3 +/- 0.5% as docosahexaenoic acid (22:6(n-3)), the predominant fatty acids being gondoic (20:1(n-3)), 21.9 +/- 0.9% and cetoleic acid (22:1(n-11)), 21.7 +/- 1.7%, which are of dietary origin. Daily caloric intake was similar to the oil-fed versus control rats. However, the oil-fed animals weighed significantly more than the controls after 2 months of oil supplementation. Redfish oil reduced serum triacylglycerols by 54% in males and 45% in females after 2 months. VLDL levels, after the same time period, were reduced by 44% in males and 39% in females. HDL lipid mass was significantly reduced in both sexes (by 27% in males and 49% in females). However, the levels remained above those of male LA/N +/+ rats of the same age and Long-Evens rats. Olive oil feeding significantly reduced serum cholesterol, triacyglycerols and phospholipids in male but only cholesterol and phospholipids in female animals. This oil had no significant effect upon VLDL total lipid levels in either sex, but significantly increased the particle diameter with a concomitant reduction in the cholesterol and phospholipid content. HDL total lipid levels were unaffected: However, HDL total cholesterol increased significantly in males only. Both oils markedly reduced serum LDL levels in both sexes.(ABSTRACT TRUNCATED AT 400 WORDS)     

Selective incorporation of n-3 and n-6 fatty acids in essential fatty acid deficient rats in response to short-term oil feeding

Essential fatty acid deficient male Sprague Dawley rats were fed for 7 days a fat-free semi-synthetic diet supplemented with 10% by weight of different oil supplements. The oil supplement was a mixture of olive, safflower and linseed oils prepared at different proportions so the dietary n-9/n-6/n-3 ratios were approximate 2/1/1, 1/2/1, 1/1/2, and 1/1/1. The fatty acid compositions of plasma and liver lipids were then examined. Our results show polyunsaturated n-6 and n-3 fatty acids were selectively incorporated into plasma and liver phospholipids, and also into plasma cholesteryl esters. A preferential incorporation of n-6 over n-3 fatty acids into plasma cholesteryl esters and phospholipids was also observed.     

Urinary excretion of diols derived from eicosapentaenoic acid during n-3 fatty acid ingestion by man.

Epoxides and fatty acid diols derived from arachidonate by the action of cytochrome P-450 appear in human urine and have biological activities. Dietary eicosapentaenoic acid gives rise to prostaglandins in vivo, but vascular effects of n-3 supplements do not all correlate with altered types or amounts of in vivo cyclooxygenase products. We investigated whether dietary eicosapentaenoic acid could also be metabolized by cytochrome P-450, by assessing the excretion of its vicinal diols. Utilizing gas chromatography/negative chemical ionization mass spectrometry, we have found that humans ingesting n-3 fatty acids excrete vicinal diols of eicosapentaenoic acid in substantial quantities.     

Effects of essential fatty acid deficiency and supplementation with docosahexaenoic acid (DHA; 22:6n-3) on cellular fatty acid compositions and fatty acyl desaturation in a cell culture model

The desaturation of [1-(14)C] 18:3n-3 to docosahexaenoic acid (DHA; 22:6n-3) is enhanced in an essential fatty acid deficient cell line (EPC-EFAD) in comparison with the parent cell line (EPC) from carp. In the present study, the effects of DHA on lipid and fatty acid compositions, and the metabolism of [1-(14)C]18:3n-3 were investigated in EPC-EFAD cells in comparison with EPC cells. DHA supplementation had only relatively minor effects on lipid content and lipid class compositions in both EPC and EPC-EFAD cells, but significantly increased the amount of DHA, 22:5n-3, eicosapentaenoic acid (EPA; 20:5n-3), total n-3 polyunsaturated fatty acids (PUFA), total PUFA and saturated fatty acids in total lipid and total polar lipid in both cell lines. Retroconversion of supplemental DHA to EPA was significantly greater in EPC cells. Monounsaturated fatty acids, n-9 and n-6PUFA were all decreased in total lipid and total polar lipid in both cell lines by DHA supplementation. The incorporation of [1-(14)C]18:3n-3 was greater into EPC-EFAD compared to EPC cells but DHA had no effect on the incorporation of [1-(14)C]18:3n-3 in either cell line. In contrast, the conversion of [1-(14)C]18:3n-3 to tetraenes, pentaenes and total desaturation products was similar in the two cell lines and was significantly reduced by DHA supplementation in both cell lines. However, the production of DHA from [1-(14)C]18:3n-3 was significantly greater in EPC-EFAD cells compared to EPC cells and, whereas DHA supplementation had no effect on the production of DHA from [1-(14)C]18:3n-3 in EPC cells, DHA supplementation significantly reduced the production of DHA from [1-(14)C] 18:3n-3 in EPC-EFAD cells. Greater production of DHA in EPC-EFAD cells could be a direct result of significantly lower levels of end-product DHA in these cells' lipids compared to EPC cells. Consistent with this, the suppression of DHA production upon DHA supplementation was associated with increased cellular and membrane DHA concentrations in EPC-EFAD cells. However, an increase in cellular DHA content to similar levels failed to suppress DHA production in DHA-supplemented EPC cells. A possible explanation is that greatly increased levels of EPA, derived from retroconversion of the added DHA, acts to offset the suppression of the pathway by DHA by stimulating conversion of EPA to DHA in DHA-supplemented EPC cells.     

Dietary supplementation with docosahexaenoic acid,but not with eicosapentaenoic acid,reduces host resistance to fungal infection in mice

The effect of dietary docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on host resistance to Paracoccidioides brasiliensis infection was investigated. Mice fed palm oil supplemented with DHA showed reduced antifungal activity in the spleen and liver, as compared with mice fed palm oil or soybean oil without supplementation with DHA. Mice fed DHA-supplemented soybean oil also showed reduced antifungal activity in the liver, but the extent of reduction was less profound. This reduction in antifungal activity was not observed with EPA-supplemented palm or EPA-supplemented soybean oil. These results suggest that two factors, DHA and palm oil in combination, are involved in reducing the host resistance. DHA-enriched palm oil was also responsible for an increase in DHA concentration and a marked decrease in arachidonic acid content in the spleen and liver. However, this group did not show elevated spleen and liver phospholipid hydroperoxide levels compared with the other groups, excluding the possibility that the reduction in antifungal activity observed with DHA-enriched palm oil is due to acceleration of in vivo lipid peroxidation. Greater infection-induced increases in spleen and serum interferon-gamma concentrations were observed in mice fed DHA-enriched palm oil compared with the other groups.     

Altered physiological responsiveness and decreased cyclic AMP levels in rat atria after dietary cod liver oil supplementation and its possible association with an increased membrane phospholipid n-3/n-6 fatty acid ratio

Rats were given a cod liver oil supplemented diet and a standard diet for 4 months. The cod liver oil supplementation resulted in a marked increase in the 20:5(n-3) and 22:6(n-3) fatty acids and a marked decrease in the 20:4(n-6) fatty acid in phosphatidylcholine and ethanolamine of the atrial membrane. Atria from the cod liver oil treated rats showed a marked decrease in contractile force, heart rate and cyclic AMP (cAMP) levels under basal conditions. Stimulation with noradrenaline (1 X 10(-6) M) during high oxygen saturation and reoxygenation resulted in an equal increase in the mechanical responses of the two groups in spite of the significantly different levels of cAMP, whereas in hypoxia, both the cAMP level and the contractile force were significantly lower in the cod liver oil treated group. These results indicate that changes in the fatty acid composition of heart membrane phospholipids is associated with changes in adenylate cyclase activity and physiological function of the rat heart and that an increase in the n-3/n-6 fatty acid ratio in membrane phospholipids of the heart results, when oxygen is abundant in enhanced cAMP-independent contractile activity.     

The effects of dietary (n-3) fatty acid supplementation on lipid dynamics and composition in rat lymphocytes and liver microsomes

Rats were fed diets devoid of (n-3) fatty acids (olive oil supplementation) or high in (n-3) fatty acids (fish oil supplementation) for a period of 10 days. In spleen lymphocytes and liver microsomes derived from animals fed fish oil diets, relatively high levels of (n-3) eicosapentaenoic (20:5), docosapentaenoic (22:5) and docosahexaenoic acids (22:6) were obtained compared to minimal levels when fed the olive oil diet. When the average lipid motional properties were examined by measuring the fluorescence anisotropy of diphenylhexatriene, no significant different was found between intact liver microsomes from animals fed the two diets. However, when lipid motion was examined in vesicles of phosphatidylcholine, isolated from the microsomes from fish oil fed animals (21.4% (n-3) fatty acids), the fluorescence anisotropy was significantly less than the corresponding phosphatidylcholine from olive oil fed animals (5.6% (n-3) fatty acids), indicating a more disordered or fluid bilayer in the presence of higher levels of (n-3) fatty acids. Phosphatidylethanolamine (n-3) fatty acids were also elevated after fish oil supplementation (41.3% of total fatty acids), compared to the level after olive oil supplementation (21.4%). The major effect of the fish oil supplementation was a replacement of (n-6) arachidonic acid by the (n-3) fatty acids and when this was 'modeled', using liposomes of synthetic lipids, 1-palmitoyl-2-arachidonyl(n-6) or docosahexaenoyl(n-3)-phosphatidylcholine, significant differences in lipid motional properties were found, with the docosahexaenoate conferring a more disordered or fluid lipid environment. Thus it appears that although lipid order/fluidity can be significantly decreased by increases in the highly unsaturated (n-3) fatty acid levels, alterations in membrane domain organization and/or phospholipid molecular species composition effectively compensated for the changes, at least as far as average lipid motional properties in the intact membranes was concerned.