Eicosapentaenoic acid,but not docosahexaenoic acid,increases mitochondrial fatty acid oxidation and upregulates 2,4-dienoyl-CoA reductase gene expression in rats

The aim of the present study was to investigate whether eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) was responsible for the triglyceride-lowering effect of fish oil. In rats fed a single dose of EPA as ethyl ester (EPA-EE), the plasma concentration of triglycerides was decreased at 8 h after acute administration. This was accompanied by an increased hepatic fatty acid oxidation and mitochondrial 2,4-dienoyl-CoA reductase activity. The steady-state level of 2,4-dienoyl-CoA reductase mRNA increased in parallel with the enzyme activity. An increased hepatic long-chain acyl-CoA content, but a reduced amount of hepatic malonyl-CoA, was obtained at 8 h after acute EPA-EE treatment. On EPA-EE supplementation, both EPA (20:5n-3) and docosapentaenoic acid (DPA, 22:5n-3) increased in the liver, whereas the hepatic DHA (22:6n-3) concentration was unchanged. On DHA-EE supplementation retroconversion to EPA occurred. No statistically significant differences were found, however, for mitochondrial enzyme activities, malonyl-CoA, long-chain acyl-CoA, plasma lipid levels, and the amount of cellular fatty acids between DHA-EE treated rats and their controls at any time point studied. In cultured rat hepatocytes, the oxidation of [1-¹⁴C]palmitic acid was reduced by DHA, whereas it was stimulated by EPA. In thein vivo studies, the activities of phosphatidate phosphohydrolase and acetyl-CoA carboxylase were unaffected after acute EPA-EE and DHA-EE administration, but the fatty acyl-CoA oxidase, the rate-limiting enzyme in peroxisomal fatty acid oxidation, was increased after feeding these n-3 fatty acids. The hypocholesterolemic properties of EPA-EE may be due to decreased 3-hydroxy-3-methylglutaryl-CoA reductase activity. Furthermore, replacement of the ordinary fatty acids, i.e., the monoenes (16:1n-7, 18:1n-7, and 18:1n-9) with EPA and some conversion to DPA concomitant with increased fatty acid oxidation is probably the mechanism leading to changed fatty acid composition. In contrast, DHA does not stimulate fatty acid oxidation and, consequently, no such displacement mechanism operates. In conclusion, we have obtained evidence that EPA, and not DHA, is the fatty acid primarily responsible for the triglyceride-lowering effect of fish oil in rats.     

Effect of dietary docosahexaenoic acid on brain composition and neural function in term infants

There is a need to determine whether there is a dietary requirement for docosahexaenoic acid (DHA, 22:6n-3) by term infants to achieve their full developmental potential. Studies of brain fatty acid composition demonstrated that infants who were breast fed had greater levels of cerebral cortex DHA than did infants who were formula fed, suggesting that DHA in the cerebrum is dependent on a supply in the diet. Some physiological studies reported that electrophysiological and behavioral assessments of visual function were improved in breast-fed infants relative to those fed formula and that this was related to the length of breast feeding. While some randomized studies of DHA supplementation of infant formula to term infants demonstrated that the visual function of formula-fed infants could be improved to breast-fed levels by adding DHA to formula, others failed to demonstrate an effect. Variations in dietary treatments and methods of assessment make comparison of the studies difficult. Further work is necessary to rigorously establish if there are long-term benefits of dietary DHA to the term infant.     

The suppression of eicosanoid synthesis by peritoneal macrophages is influenced by the ratio of dietary docosahexaenoic acid to linoleic acid

The efficacy of docosahexaenoic acid (DHA) in suppressing eicosanoic synthesis by peritoneal macrophagesin vivo was influenced by the relative amount of dietary DHA when linoleic acid (LA) was held constant. Increasing DHA from 0 to 37% of the fatty acids in diets containing 10 weight % fat (of which LA was 40%) caused an eleven-fold increase in the DHA content of macrophages. Limited retroconversion of DHA to eicosapentaenoic acid was observed. Macrophages in animals consuming DHA synthesized significantly lower amounts of leukotriene E₄, prostaglandin E₂ and 6-keto prostaglandin F_1α in vivo upon stimulation with zymosan. The maximum inhibition of eicosanoid synthesis was observed when the dietary DHA/LA ratio was 0.16 and no further inhibition occurred when the ratio was increased up to 0.81.     

Dietary conjugated linoleic acid did not alter immune status in young healthy women

The purpose of this study was to examine whether conjugated linoleic acid (CLA) supplementation in human diets would enhance indices of immune status as reported by others for animal models. Seventeen women, 20–41 yr, participated in a 93-d study conducted in two cohorts of 9 and 8 women at the Metabolic Research Unit of Western Human Nutrition Research Center. Seven subjects were fed the basal diet (19, 30 and 51% energy from protein, fat, and carbohydrate, respectively) throughout the study. The remaining 10 subjects were fed the basal diet for the first 30 d, followed by 3.9 g CLA (Tonalin)/d for the next 63 d. CLA made up 65% of the fatty acids in the Tonalin capsules, with the following isomeric composition: t10, c12, 22.6%; c11, t13, 23.6%; c9, t11, 17.6%; t8, c10, 16.6%; and other isomers 19.6%. Most indices of immune response were tested at weekly intervals, three times at the end of each period (stabilization/intervention); delayed-type hypersensitivity (DTH) to a panel of six recall antigens was tested on study day 30 and 90; all subjects were immunized on study day 65 with an influenza vaccine, and antibody titers were examined in the sera collected on day 65 and 92. None of the indices of immune status tested (number of circulating white blood cells, granulocytes, monocytes, lymphocytes, and their subsets, lymphocytes proliferation in response to phytohemagglutinin, and influenza vaccine, serum influenza antibody titers, and DTH response) were altered during the study in either dietary group. Thus, in contrast to the reports with animal models, CLA feeding to young healthy women did not alter any of the indices of immune status tested. These data suggest that short-term CLA supplementation in healthy volunteers is safe, but it does not have any added benefit to their immune status. Parts of data included here were published as an abstract for the Experimental Biology 2000, meeting.     

Dietary docosahexaenoic acid and immunocompetence in young healthy men

The purpose of this study was to examine the effect of dietary docosahexaenoic acid (DHA), in the absence of eicosapentaenoic acid, on human immune response (IR). A 120-d study with 11 healthy men was conducted at the Metabolic Research Unit of the Western Human Nutrition Research Center. Four subjects (control group) were fed the stabilization or basal diet (15, 30, and 55% energy from protein, fat, and carbohydrate, respectively) throughout the study; the remaining seven subjects (DHA group) were fed the basal diet for the first 30 d, followed by 6 g DHA/d for the next 90 d. DHA replaced an equivalent amount of linoleic acid; the two diets were comparable in their total fat and all other nutrients. Both diets were supplemented with 20 mg d-α-tocopherol acetate per day. Indices of IR were examined on study day 22, 30, 78, 85, 106, and 113. Addition of DHA at moderately high levels did not alter the proliferation of peripheral blood mononuclear cells cultured with phytohemag-glutinin or concanavalin A, or the delayed hypersensitivity skin response. Also, additional DHA did not alter the number of T cells producing interleukin 2 (IL2), the ratio between the helper/suppressor T cells in circulation, or the serum concentrations of immunoglobulin G, C3, and interleukin 2 receptor (IL2R). DHA supplementation, however, caused a significant (P=0.0001) decrease in the number of circulating white blood cells which was mainly due to a decrease in the number of circulating granulocytes. The number of lymphocytes in peripheral circulation was not affected by Dietary DHA enrichment, but the percentage of lymphocytes in white blood cells increased because of a reduction in granulocyte numbers. None of these indices was changed in the control group. Our results show that when total fat intake is low and held constant, DHA consumption does not inhibit many of the lymphocyte functions which have been reported to be inhibited by fish oil consumption.     

Influence of dietary linoleic acid andtrans fatty acids on the fatty acid profile of cardiolipins in rats

Cardiolipins (CL) have unique fatty acid profiles with generally high levels of polyunsaturated fatty acids, primarily 18∶2n−6, and low levels of saturated fatty acids. In order to study the effect of dietary fatty acid isomers on the fatty acid composition of cardiolipins, rats were fed partially hydrogenated marine oils (HMO), rich in 16∶1, 18∶1, 20∶1, and 22∶1 isomeric fatty acids, supplemented with linoleic acid at levels ranging from 1.9% to 14.5% of total fat. Although the dietary fats contained 33%trans fatty acids, the levels oftrans fatty acids in CL were below 2.5% in all organs. The fatty acid profiles of cardiolipins of liver, heart, kidney and testes showed different responses to dietary linoleic acid level. In liver, the contents of 18∶2 reflected the dietary levels. In heart and kidney, the levels of 18∶2 also parallelled increasing dietary levels, but in all groups fed HMO, levels of 18∶2 were considerably higher than in the reference group fed palm oil. In testes, the 18∶2 levels were unaffected by the dietary level of 18∶2 and HMO.     

Effects of dietary conjugated linoleic acid on the expression of uncoupling proteins in mice and rats

CLA inhibits mammary cancer and reduces body fat accumulation in rodents. It is not known whether uncoupling proteins (UCP), which are modulators of energy balance and metabolism, play a role in these actions of CLA. To determine the effects of dietary CLA on the expression of UCP in various tissues, 5-wk-old Sprague-Dawley rats and C57BI/6 mice were fed diets containing 1% CLA for 3 wk. CLA treatment reduced adipose depot weights in both rats and mice but had no significant effects on body weight. There was a species-specific effect of CLA on the expression of UCP. Whereas CLA did not affect the expression of UCP in most tissues in rats, mice fed CLA had increased expression of UCP2 in the mammary gland, brown adipose tissue (BAT), and white adipose tissue (WAT). Furthermore, UCP1 and UCP3 mRNA and protein levels in BAT were significantly lower in CLA-fed mice compared to controls. Skeletal muscle UCP3 mRNA was unchanged, but UCP3 protein levels were significantly increased in mice, suggesting translational or posttranslational regulation of this protein. Results from this study suggest that alterations in the expression of UCP in mice may be related to the previously reported effects of dietary CLA in lowering adiposity and increasing FA oxidation. In rats, however, induction of UCP is not likely to be responsible for fat reduction or for the inhibitory action of CLA on mammary carcinogenesis.     

Effect of dietary docosahexaenoic acid on desaturation and uptake in vivo of isotope-labeled oleic, linoleic, and linolenic acids by male subjects

The effect of dietary docosahexaenoic acid (22∶6n−3, DHA) on the metabolism of oleic, linoleic, and linolenic acids was investigated in male subjects (n=6) confined to a metabolic unit and fed diets containing 6.5 or <0.1 g/d of DHA for 90 d. At the end of the diet period, the subjects were fed a mixture of deuterated triglycerides containing 18∶1n−9[d6], 18∶2n−6[d2], and 18∶3n−3[d4]. Blood samples were drawn at 0, 2, 4, 6, 8, 12, 24, 48, and 72 h. Methyl esters of plasma total lipids, triglycerides, phospholipids, and cholesterol esters were analyzed by gas chromatography-mass spectrometry. Chylomicron triglyceride results show that the deuterated fatty acids were equally well absorbed and diet did not influence absorption. Compared to the low-DHA diet (LO-DHA), clearance of the labeled fatty acids from chylomicron triglycerides was modestly higher for subjects fed the high DHA diet (HI-DHA). DHA supplementation significantly reduced the concentrations of most n-6[d2] and n-3[d4] long-chain fatty acid (LCFA) metabolites in plasma lipids. Accumulation of 20∶5n−3[d4] and 22∶6n−3[d4] was depressed by 76 and 88%, respectively. Accumulations of 20∶3n−6[d2] and 20∶4n−6[d2] were both decreased by 72%. No effect of diet was observed on acyltransferase selectivity or on uptake and clearance of 18∶1n−9[d6], 18∶2n−6[d2], and 18∶3n−3[d4]. The results indicate that accumulation of n−3 LCFA metabolites synthesized from 18∶3n−3 in typical U.S. diets would be reduced from about 120 to 30 mg/d by supplementation with 6.5 g/d of DHA. Accumulation of n−6 LCFA metabolites synthesized from 18∶2n−6 in U.S. diets is estimated to be reduced from about 800 to 180 mg/d. This decrease is two to three times the amount of n−6 LCFA in a typical U.S. diet. These results support the hypothesis that health benefits associated with DHA supplementation are the combined result of reduced accretion of n−6 LCFA metabolites and an increase in n−3 LCFA levels in tissue lipids.     

Conjugated linoleic acid isomers reduce blood cholesterol levels but not aortic cholesterol accumulation in hypercholesterolemic hamsters

The aim of the present study was to characterize plasma lipids and lipoprotein cholesterol and glucose concentrations in hamsters fed either cis-9, trans-11 CLA (9c, 11t CLA); trans-10, cis-12 CLA (10t, 12c CLA); or linoleic acid (LA) on the accumulation of aortic cholesterol in hypercholesterolemic hamsters. One hundred male F₁B strain Syrian Golden Hamsters (Mesocricetus auratus) (BioBreeders Inc., Watertown, MA) approximately 9 wk of age were housed in individual stainless stel hanging cages at room temperature with a 12-h light/dark cycle. Hamsters were given food and water ad libitum. Following a 1-wk period of acclimation, the hamsters were fed a chow-based (nonpurified) hypercholesterolemic diet (HCD) contaning 10% coconut oil (92% saturated fat) and 0.1% cholesterol for 2 wk. After an overnight fast, the hamsters were bled and plasma cholesterol concentrations were measured. The hamsters were then divided into 4 groups of 25 based on similar mean plasma VLDL and LDL cholesterol (non HDL-C) concentrations. Group 1 remained on the HCD (control). Group 2 was fed the HCD plus 0.5% 9c, 11t CLA isomer. Group 3 was fed the HCD plus 0.5% 10t, 12c CLA isomer. Group 4 was fed the HCD plus 0.5% LA. Compared with the control, both CLA isomers and LA had significantly lower plasma total cholesterol and HDL cholesterol concentrations (P<0.001) after 12 but not 8 wk of treatment and were not significantly different from each other. Also, both CLA isomers had significantly lower plasma non HDL-C concentrations (P<0.01) compared with the control after 12 but not 8 wk of treatment and were not significantly different from each other or the LA-fed hamsters. Plasma TG concentrations were significantly higher (P<0.004) with the 10t, 12c CLA isomer compared with the other treatments at 8 but not at 12 wk of treatment. Plasma TG concentrations were also significantly lower (P<0.03) with the 9c, 11t CLA isomer compared with the control at 12 wk of treatment. Also, the 10t, 12c CLA isomer and LA had significantly higher plasma glucose concentrations compared with the control and 9c, 11t CLA isomer (P<0.008) at 12 wk of treatment whereas at 8 wk, only the LA treatment had significantly higher plasma glucose concentrations (P<0.001) compared with the 9c, 11t CLA isomer. Although liver weights were significantly higher in 10t, 12c CLA isomer-fed hamsters, liver total cholesterol, free cholesterol, cholesterol ester, and TG concentrations were significantly lower in these hamsters compared with hamsters fed the control, 9c, 11t CLA isomer, and LA diets (P<0.05). The 9c, 11t CLA isomer and LA diets tended to reduce cholesterol accumulation in the aortic arch, whereas the 10t, 12c CLA isomer diet tended to raise cholesterol accumulation compared with the control diet; however, neither was significant. In summary, no differences were observed between the CLA isomers for changes in plasma lipids or lipoprotein cholesterol concentrations. However, the 9c, 11t CLA isomer did appear to lower plasma TG and glucose concentrations compared with the 10t, 12c CLA isomer. Such differences may increase the risk of insulin resistance and type 2 diabetes in humans when the 10t, 12c CLA isomer is fed separately.     

Dietary docosahexaenoic acid affects stearic acid desaturation in spontaneously hypertensive rats

Docosahexaenoic acid (DHA, 22∶6n−3) is an n−3 polyunsaturated fatty acid which attenuates the development of hypertension in spontaneously hypertensive rats (SHR). The effects of DHA on delta-9-desaturase activity in hepatic microsomes and fatty acid composition were examined in young SHR. Two groups of SHR were fed either a DHA-enriched diet or a control diet for 6 wk. Desaturase activity and fatty acid composition were determined in hepatic microsomes following the dietary treatments. Delta-9-desaturase activity was decreased by 53% in DHA-fed SHR and was accompanied by an increase in 16∶0 and a reduction in 16∶1n−7 content in hepatic microsomes. The DHA diet also increased the levels of eicosapentaenoic acid (20∶5n−3) and DHA. The n−6 fatty acid content was also affected in DHA-fed SHR as reflected by a decrease in gamma-linolenic acid (18∶3n−6), arachidonic acid (20∶5n−6), adrenic acid (22∶4n−6), and docosapentaenoic acid (22∶5n−6). A higher proportion of dihomo-gamma-linolenic acid (20∶3n−6) and a lower proportion of 20∶4n−6 is indicative of impaired delta-5-desaturase activity. The alterations in fatty acid composition and metabolism may contribute to the antihypertensive effect of DHA previously reported.     

Natural and accelerated docosahexaenoic acid accumulation in the prenatal rat brain

The quantity and distribution of docosahexaenoic acid (DHA) in major brain phospholipids (PL) was examined in the fetal rat brain before birth, using thin-layer and capillary column gas chromatography. A rapid increment of DHA content of about 187 μg/g brain/day was observed between 17 to 20 days gestation, as opposed to 39.3±2.9 μg/g brain/day prior to that. Single intraamniotic injections of 5 μL ethyl-docosahexaenoate (Et-DHA) 12 μM, 4.25 mg) administered to 17-day-old fetuses were used to examine the uptake of DHA into brain PL. Three days following injection, the amount of n-3 polyunsaturated fatty acids increased by 28% compared to ethyl-oleate (Et-Ole) injected fetuses. Compared to the n-6 fatty acid family, the relative amount of DHA increased in the phosphoatidylserine (PS), phosphatidylethanolamine and phosphatidylcholine (PC) lipids by 15 (P=0.02), 13 and 14%, respectively. A major increase in the pool size of phosphatidylinositol and PS (110 and 50.3%, respectively), and a decrease in PC (8.2%) were observed 3 d after Et-DHA as compared to Et-Ole administration. The data suggest that a single intraamniotic administration of Et-DHA can modulate membrane PL content and alter PUFA composition.     

Dietary linoleic acid and polyunsaturated fatty acids in rat brain and other organs. Minimal requirements of linoleic acid

Starting three weeks before mating, 12 groups of female rats were fed different amounts of linoleic acid (18∶2n−6). Their male pups were killed when 21-days-old. Varying the dietary 18∶2n−6 content between 150 and 6200 mg/100 g food intake had the following results. Linoleic acid levels remained very low in brain, myelin, synaptosomes, and retina. In contrast, 18∶2n−6 levels increased in sciatic nerve. In heart, linoleic acid levels were high, but were not related to dietary linoleic acid intake. Levels of 18∶2n−6 were significantly increased in liver, lung, kidney, and testicle and were even higher in muscle and adipose tissue. On the other hand, in heart a constant amount of 18∶2n−6 was found at a low level of dietary 18∶2n−6. Constant levels of arachidonic acid (20∶4n−6) were reached at 150 mg/100 g diet in all nerve structures, and at 300 mg/100g diet in testicle and muscle, at 800 mg/100 g diet in kidney, and at 1200 mg/100 g diet in liver, lung, and heart. Constant adrenic acid (22∶4n−6) levels were obtained at 150, 900, and 1200 mg/100 g diet in myelin, sciatic nerve, and brain, respectively. Minimal levels were difficult to determine. In all fractions examined accumulation of docosapentaenoic acid (22∶5n−6) was the most direct and specific consequence of increasing amounts of dietary 18∶2n−6. Tissue eicosapentaenoic acid (20∶5n−3) and 22∶5n−3 levels were relatively independent of dietary 18∶2n−6 intake, except in lung, liver, and kidney. In several organs (muscle, lung, kidney, liver, heart) as well as in myelin, very low levels of dietary linoleic acid led to an increase in 20∶5n−3. Dietary requirements for 18∶2n−6 varied from 150 to 1200 mg/100 g food intake, depending on the organ and the nature of the tissue fatty acid. Therefore, the minimum dietary requirement is estimated to be about 1200 mg/100 g (i.e., the level that ensures stable and constant amounts of arachidonic acid).     

The effect of dietary docosahexaenoic acid on plasma lipoproteins and tissue fatty acid composition in humans

Normal, healthy male volunteers (n=6) were fed diets [high docosahexaenoic acid-DHA] containing 6 g/d of DHA for 90 d. The stabilization (low-DHA) diet contained less than 50 mg/d of DHA. A control group (n=4) remained on the low-DHA diet for the duration of the study (120 d). Blood samples were drawn on study days 30 (end of the stabilization period), 75 (midpoint of the intervention period), and 120 (end of the intervention period). Adipose tissue (AT) samples were taken on days 30 and 120. The plasma cholesterol (C), low density lipoprotein (LDL)-C and apolipoproteins (apo) [Al, B, and lipoprotein (a)] were unchanged after 90 d, but the triglycerides (TAG) were reduced from a mean value of 76.67±24.32 to 63.83±16.99 mg/dL (n=6, P<0.007 using a paired t-test) and the high density lipoprotein (HDL)-C increased from 34.83±4.38 mg/dL to 37.83±3.32 mg/dL (n=6, P<0.017 using a paired t-test). The control group showed no significant reduction in plasma TAG levels. Apo-E, however, showed a marked increase in the volunteers’ plasma after 90 d on the high-DHA diet, from 7.06±4.47 mg/dL on study day 30 to 12.01±4.96 mg/dL on study day 120 (P<0.002 using a paired t-test). The control subjects showed no significant change in the apo-E in their plasma (8.46±2.90 on day 30 vs. 8.59±2.97 on day 120). The weight percentage of plasma DHA rose from 1.83±0.22 to 8.12±0.76 after 90 d on the high-DHA diet. Although these volunteers were eating a diet free of eicosapentaenoic acid (EPA), plasma EPA levels rose from 0.38±0.05 to 3.39±0.52 (wt%) after consuming the high-DHA diet. The fatty acid composition of plasma lipid fractions—cholesterol esters, TAG, and phospholipid—showed marked similarity in the enrichment of DHA, about 10%, after the subjects consumed the high-DHA diet. The DHA content of these plasma lipid fractions varied from less than 1% (TAG) to 3.5% (phospholipids) at baseline, study day 30. EPA also increased in all plasma lipid fractions after the subjects consumed the high-DHA diet. There were no changes in the plasma DHA or EPA levels in the control group. Consumption of DHA also caused an increase in AT levels of DHA, from 0.10±0.02 to 0.31±0.07 (wt%) (n=6, P<0.001 using a paired t-test), but the amount of EPA in their AT did not change. Thus, dietary DHA will lower plasma TAG without EPA, and DHA is retroconverted to EPA in significant amounts. Dietary DHA appears to enhance apo-E synthesis in the liver. It appears that DHA can be a safe and perhaps beneficial supplement to human diets.     

Early dietary intervention with structured triacylglycerols containing docosahexaenoic acid. Effect on brain, liver, and adipose tissue lipids

Newborn rats were fed liquid diets containing 7 wt% fat in which 3.8% of the total fatty acids were 22:6n-3. The fats were either a specific structured oil with 22:6n-3 mostly located in the sn-2 position or a randomized oil with 22:6n-3 equally distributed in the triacylglycerol (TAG) molecules. The oils were manufactured by interesterification of fish oil TAG with free fatty acids from butterfat. The pups were tube-fed three times a day and stayed with their dams during the night. After 14 d they were fed solid diets containing the same oils for the next 7 d. A reference group stayed with the dams and received ordinary rat chow at weaning. In general no significant differences between the two dietary treatments were observed in the tissues examined except for adipose tissue. The levels of 22:6n-3 were significantly increased in brain phosphatidylcholines (PC) and phosphatidylserines (PS) of both experimental groups compared with the reference group after three weeks, whereas no differences were found in brain phosphatidylethanolamines (PE) and phosphatidylinositols (PI). In all groups and all phospholipids examined, the levels of 20:4n-6 generally decreased from 1 to 3 wk and were significantly lower in the experimental groups compared with the reference group at 3 wk except for PI. In liver, PC and PE 22:6n-3 remained constant in the experimental groups but decreased significantly in the reference group, whereas in liver PS 22:6n-3 increased in all groups, but reached significantly higher levels in the experimental groups than in the reference group. In adipose tissue, 22:6n-3 increased in the experimental groups during the study period, but decreased in the reference group, suggesting that a surplus of dietary 22:6n-3 was stored.     

Effects of dietary linolenate on the fatty acid composition of brain lipids in rats

Weanling male rats were fed hydrogenated coconut oil to induce essential fatty acid (EFA) deficiency. After 15 weeks, the rats were divided into six groups. Five groups were fed graded amounts of purified linolenate (18∶3ω3) with a constant amount of linoleate (18∶2ω6) for six weeks. Fatty acid composition was determined in brain lipids. Increasing dietary 18∶3ω3 resulted in a decrease in arachidonic acid (20∶4ω6), docosatetraenoic acid (22∶4ω6) and docosapentaenoic acid (22∶5ω6), whereas 18∶2ω6 and eicosatrienoic acid (20∶3ω6) were increased both in total lipids and phospholipids. These results suggest that dietary 18∶3ω3 exerts its inhibitory effect mainly on the desaturation of 20∶ω6 to 20∶4ω6 in brain lipids. Linolenate was undetectable in brain lipids from any dietary treatments. The levels of eicosapentaenoic acid (20∶5ω3) in groups receiving dietary 18∶3ω3 were not different from that of the group receiving no 18∶3ω3. These results indicate that, in the brain, 18∶3ω3 is rapidly converted mainly to 22∶6ω3 without being accumulated and imply that dietary 18∶3ω3 can modulate the level of precursor of diene prostaglandins (PG) but not that of triene PG in the rat brain.     

Dietary conjugated linoleic acid increases endurance capacity and fat oxidation in mice during exercise

Ingestion of CLA activates β-oxidation and causes loss of body fat in rodents. We investigated the effects of dietary CLA on endurance capacity and energy metabolism during exercis in mice. Five-week-old male BALB/c mice were fed a control diet containing 1.0% linoleic acid or a diet containing 0.5% CLA that replaced an equivalent amount of linoleic acid for 1 wk. The maximum swimming time until fatigue was significantly higher in the CLA-fed group than in the control group. During treadmill running, the respiratory exchange ratio was significantly lower in the CLA-fed group, but oxygen consumption did not differ significantly between groups, suggesting that FA contributed more as an energy substrate in the CLA-fed mice. The muscle lipoprotein lipase activity was significantly higher in the CLA-fed group than in the control group. These results suggest that CLA ingestion increases endurance exercise capacity by promoting fat oxidation during exercise.     

The incorporation of orally fed radioactive γ-linolenic acid and linoleic acid into the liver and brain lipids of suckling rats

The incorporation of radioactivity from orally administered gamma-linolenic acid-1--14C and linoleic acid--3H into the liver, plasma, and brain lipids of suckling rats was studied. Significantly more radioactivity from the former compound was incorporated into the liver and brain lipids 22 hr after dosing. The distribution of the radioactivity in the fatty acids of the liver and brain lipids was different for each isotope. Most of the -3H was still associated with linoeic acid, whereas most of the -14C was in the 20:3 and 20:4omega6 fractions. These results suggest that the desaturation of linoleic to gamma-linolenic acid in vivo is a rate-limiting step in the conversion of linoleic to arachidonic acid.     

Biochemical effects of dietary linoleic/α-linolenic acid ratio in term infants

Recent statements concerning linoleic (LA) and α-linolenic acid (LNA) intakes for infants include a desirable range of LA/LNA ratios. To evaluate several dietary LA/LNA ratios, the fatty acid patterns of plasma and erythrocyte phospholipid fractions, as well as plasma total lipid fractions, were determined shortly after birth and at 21, 60, and 120 d of age in term infants fed formula with 16% of fat as LA and either 0.4, 0.95, 1.7, or 3.2% as LNA (LA/LNA ratios of approximately 44, 18, 10, and 5). The content of all n-3 fatty acids in both plasma fractions was higher at all times in infants who received the highest LNA intake; however, the docosahexaenoic acid (DHA) content was only half that shortly after birth or reported in breast-fed infants of comparable ages. The LA content of plasma lipids of all groups was higher at all times than shortly after birth but did not differ among groups. The arachidonic acid (AA) content was higher in infants who received the lowest LNA intake, but only half that at birth or reported in breast-fed infants. In contrast, the DHA content of the erythrocyte phospholipid fraction did not differ among groups until 120 d of age when it was higher in those who received the highest LNA intake and the AA content of this fraction did not differ among groups at any time. These data demonstrate that dietary LA/LNA ratios between 5 and 44 do not result in plasma or erythrocyte lipid levels of DHA or plasma lipid levels of AA similar to those at birth or reported by others in breast-fed infants. However, the data indicate that the LA/LNA ratio of the formula is an important determinant of the amounts of DHA and AA required to achieve plasma and erythrocyte levels of these fatty acids similar to those of breast-fed infants. Based on a presentation at the AOCS Annual Meeting & Expo in San Antonio, Texas, May 7–11, 1995.     

Increased hepatic β-oxidation of docosahexaenoic acid, elongation of eicosapentaenoic acid, and acylation of lysophosphatidate in rats fed a docosahexaenoic acid-enriched diet

Rats were fed a diet supplemented with corn oil (n-3 deficient), soy oil, or a mixture containing 8% 22∶6n-3 ethyl ester for 6 wk. The hepatic capacities for the β-oxidation and synthesis of 22∶6n-3, in addition to the acylation of lysophosphatidate, were tested in vitro. In rats that were fed a 22∶6n-3-enriched diet, both the β-oxidation of 22∶6n-3 and elongation of 20∶5n-3 were enhanced compared to those in rats fed the other diets. Acylation of lysophosphatidate was also enhanced in rats fed a 22∶6n-3-enriched diet, while the rate of dephosphorylation of phosphatidate was not changed. The amount of 22∶6n-3 in the liver was much less than that consumed in a docosahexaenoic acid-enriched diet. These results suggest that a significant amount of dietary 22∶6n-3 was degraded via β-oxidation, and that a portion of the retroconverted 20∶5n-3 was recycled for the synthesis of 22∶6n-3. The recycling of 20∶5n-3 might contribute to the low level of 22∶6n-3 in rats fed an n-3-deficient diet.     

Differential effects of dietary linoleic and α-linolenic acid on lipid metabolism in rat tissues

Comparative effects of feeding dietary linoleic (safflower oil) and α-linolenic (linseed oil) acids on the cholesterol content and fatty acid composition of plasma, liver, heart and epididymal fat pads of rats were examined. Animals fed hydrogenated beef tallow were used as isocaloric controls. Plasma cholesterol concentration was lower and the cholesterol level in liver increased in animals fed the safflower oil diet. Feeding the linseed oil diet was more effective in lowering plasma cholesterol content and did not result in cholesterol accumulation in the liver. The cholesterol concentration in heart and the epididymal fat pad was not affected by the type of dietary fatty acid fed. Arachidonic acid content of plasma lipids was significantly elevated in animals fed the safflower oil diet and remained unchanged by feeding the linseed oil diet, when compared with the isocaloric control animals fed hydrogenated beef tallow. Arachidonic acid content of liver and heart lipids was lower in animals fed diets containing safflower oil or linseed oil. Replacement of 50% of the safflower oil in the diet with linseed oil increased α-linolenic, docosapentaenoic and docosahexaenoic acids in plasma, liver, heart and epididymal fat pad lipids. These results suggest that dietary 18∶2ω6 shifts cholesterol from plasma to liver pools followed by redistribution of 20∶4ω6 from tissue to plasma pools. This redistribution pattern was not apparent when 18∶3ω3 was included in the diet.