The in vivo incorporation of labeled linoleic acid, α-linolenic acid and arachidonic acid into rat liver lipids

The incorporation of 1-¹⁴C-linoleic acid, 1-¹⁴C-α-linolenic acid and 1-¹⁴C-arachidonic acid into rat liver lipids was measured and the per cent distribution of radioactivity into the different lipid fractions determined. Normal rats were injected into the portal vein with the labeled solutions during a one minute period. Livers were quickly frozen, pulverized, and the lipids extracted and fractioned by thin layer chromatography. No significant differences were observed in the amounts of labeled fatty acids incorporated per gram of rat liver. While 1-¹⁴C-linoleic acid and 1-¹⁴C-α-linolenic acid were found in appreciable amounts in the 1,2 diacylglycerol fraction, about one fifth as much 1-¹⁴C-arachidonic acid was esterified in this fraction. 1-¹⁴C-arachidonic acid was the leading acid esterified in the phospholipid fractions.     

Effect of ATP on the microsomal desaturation of unsaturated fatty acids

The effect of ATP on the microsomal desaturation of linoleic acid to γ-linolenic acid was studied in a system in vitro with the following results: (1) preincubation of rat liver microsomes with ATP alone in N₂ or in the presence of CoA and Mg⁺⁺ followed by subsequent incubation with 1-¹⁴C-linoleic acid plus NADH in O₂ resulted in enhancement of 1-¹⁴C-linoleic acid desaturation when compared with control samples in which no preincubation was performed; (2) the preincubation of the microsomes with ATP, Mg⁺⁺ and CoA in the presence of 1-¹⁴C-linoleic acid decreased the desaturation of the labeled acid to γ-linolenic acid upon subsequent incubation with NADH, as a consequence of incorporation of the acid into the microsomal lipids; (3) the increase of linoleic acid desaturation depended on the ATP concentration during preincubation and followed a sigmoidal curve. It was specific for ATP, and neither GTP, CTP, ADP nor AMP produced a similar effec. However, GTP or CTP could replace ATP as a cofactor in the microsomal desaturation of free linoleic acid to γ-linolenic, suggesting that directly or indirectly they may activate conversion of the free acid to linoleyl-CoA; (4) preincubation of microsomes with ATP activated the acylation of CoA. However, this activation showed no quantitative correlation with enhancement of the desaturation reaction; (5) addition of ATP also stimulated conversion of linoleyl-CoA to γ-linolenic acid. This enhancement was not related to inhibition of the linoleyl-CoA hydrolase; (6) however, in spite of these results, preincubation with ATP did not increase the initial velocity of linoleic acid or linoleyl-CoA desaturation; (7) preincubation of microsomes with ATP also increased the 6-desaturation of oleic acid and α-linolenic acid but did not increase the 9-desaturation of plamitic and stearic acid.     

Fats in indian diets and their nutritional and health implications

To arrive at fat requirements for Indians; the contribution of invisible fat should be determined. Total lipids were extracted from common Indian foods, and their fatty acid compositions were determined. This data and information on intake of various foods were used to estimate the contents of “invisible” fat and fatty acids in Indian diets. Taking into account World Health Organization (WHO) guidelines and the invisible-fat intake of Indians, recommendations were made for lower and upper limits of visible fats. In the rural poor, the “visible”-fat intakes are much lower than estimated minimum requirements. Therefore, to meet the energy needs of low-income groups, particularly young children, visible-fat intakes must be increased to recommended levels. The urban high-income group, however, should reduce dietary fat. Data on intake of various fatty acids in total diet shows that even the recommended lower limit of oil can meet linoleic acid requirements. Intake of α-linolenic acid is low, however. Increase in dietary n-3 polyunsaturated fatty acid (PUFA) produces hypolipidemic, anti-inflammatory, and antithrombotic effects. Effects of n-3 PUFA on blood lipids, platelet fatty acid composition, and platelet aggregation were therefore investigated in Indian subjects consuming cereal-based diets. Supplementation of fish oils (long-chain n-3 PUFA) as well as the use of rapeseed oil (α-linolenic acid) produced beneficial effects. Since the requirements of α-linolenic acid and/or long-chain n-3 PUFA are related to linoleic acid intake, use of more than one oil (correct choice) is recommended for providing a balanced intake of various fatty acids. Analysis of Indian food showed that some foods are good sources of α-linolenic acid. Regular consumption of these foods can also improve the quality of fat in Indian diets. Nonvegetarians, however, have the choice of eating fish to accomplish this.     

Composition and biosynthesis of fatty acids inPyramimonas grossii

The green algaPyramimonas grossii orginating in the coastal waters of the Atlantic Ocean Argentina was subcultured until a monoalgal culture was obtained. The fatty acid composition of the alga grown in a mineral medium at 12 C was determined by gas liquid chromatography (GLC) on 2 columns. The major fatty acids were oleic, linoleic, palmitic and α-linolenic acids, but the 20-carbon polyunsaturated acids, 20∶4ω6 and 20∶5ω3, respectively, belonging to the linoleic and α-linolenic series, were also found. Incubation with [¹⁴C] oleate, [¹⁴C] acetate, [¹⁴C] linoleate and [¹⁴C] α-linolenate suggests that linoleate is not directly converted to α-linolenate. [¹⁴C] Acetate was easily converted to palmitic, palmitoleic and oleic acids. However, after 48 hr of incubation, only traces of radioactivity were detected in linoleic acid and no label was found in α-linolenic acid.     

Metabolic transformation of intracraneally injected [1-14C]linoleic and [1-14C]α-linolenic acids in malnourished developing rats

The effect of a low protein diet during pregnancy and lactation on the fatty acid composition of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) from brains of ten-day-old rats was studied. The results indicated that partial deprivation of protein during early development was associated with an increase in the fatty acids of the n−9 family in PC. The fatty acids of the linoleic acid series decreased in PE but were not modified in PC. These minor changes did not affect the double bond index values either in PC or in PE. The effect of protein depletion on thein vivo metabolic transformation of intracraneally injected [1-¹⁴C]linoleic and [1-¹⁴C]α-linolenic acids was also studied. The percentage distribution of the labeled precursors and their derivatives among PC and PE differed from that of mass distribution. These results indicate that the direct uptake of polyunsaturated fatty acids from the blood and/or the low turnover rate of these acids incorporated into PC and PE might be involved in maintaining the fatty acid pattern of these brain lipids.     

Acyl group distributions in tissue lipids of rats fed evening primrose oil (λ-linolenic plus linoleic acid) or soybean oil (α-linolenic plus linoleic acid)

Three groups of rats were fed diets with either 10 weight percent (wt%) of evening primrose oil, safflower oil or soybean oil for 11 weeks. Diets contained 7.1 wt% linoleic acid +0.8 wt% γ-linolenic acid, 7.6 wt% linoleic acid, or 5.3 wt% linoleic acid +0.7 wt% α-linolenic acid, respectively. In liver mitochondria as well as in heart, dietary γ-linolenic acid did not affect the fatty acid profiles of phosphatidylcholnes (PC), phosphatidylethanolamines (PE) or cardiolipins (CL), whereas dietary α-linolenic acid caused an increased formation of (n−3) polyunsaturated fatty acids (PUFA). The liver Δ6− and Δ5-desaturase activities determined in vitro were not affected by the dietary fats. In brain PE, which are rich in C22− and C20-(n−3) PUFA, as well as in testes PC and PE, which are rich in (n−6) PUFA, no effects were found from a partial replacement of dietary linoleic acid with γ-linolenic acid or α-linolenic acid. In kidney PC, PE, phosphatidylinositol (PI) and CL, 20∶3(n−6) was moderately elevated to ca. 1% following intake of γ-linolenic acid, whereas partial replacement of linoleic acid with α-linolenic acid was followed by increased deposition of 22∶6(n−3) in PC and PE of testes and kidney. Thus, no general effect of evening primrose oil on the content of (n−6) PUFA in rat tissue phospholipids was observed, wheras a significant incorporation of γ-linolenic acid into liver and adipose tissue triglycerides was found.     

Dietary manipulation of long-chain polyunsaturated fatty acids in the retina and brain of guinea pigs

High levels of n−6 docosapentaenoic acid (22∶5n−6) have been reported in the retina of guinea pigs fed commercially-prepared grain-based rations (commercial diet). In rats and monkeys, high levels of 22∶5n−6 are an indicator of n−3 polyunsaturated fatty acid (PUFA) deficiency. We have examined the fatty acid composition of the retina and brain in guinea pigs fed a commercial diet or one of three semi-purified diets containing three different levels of n−3 PUFA. The diets comprised a diet deficient in n−3 PUFA (semi-purified diet containing safflower oil), two diets containing α-linolenic acid (standard commercial laboratory diet and semi-purified diet containing canola oil), and a diet containing α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid (DHA) (semi-purified diet containing canola oil, safflower oil, and fish oil). Two groups of guinea pigs were given the diets from day 1 to 4 wk or day 1 to 8 wk, when they were sacrificed and the retinal tissues were extracted and analyzed for PUFA content by gas-liquid chromatography. Fatty acid analyses of the retinal phospholipids of the four-week-old animals revealed that the group fed DHA (from the fish oil) had the highest level of DHA (32%), compared with values of 19 and 13% for the groups fed canola oil diet and commercial diet, respectively, and 2% for the group fed the diet deficient in n−3 PUFA. The levels of 22∶5n−6 in the retinal lipids were inversely related to the DHA values, being 0.6, 6.6, 11.4, and 20.6 for the fish oil, canola oil, commercial diet, and safflower oil diet groups, respectively. The long-chain PUFA profiles in the brain phospholipids of the four-week-old group were similar to those from the retina. The retinal PUFA values for the eight-week-old animals were similar to the four-week-old group. The safflower oil diet induced a greater deficit of DHA in retinal lipids than has been reported in rats and monkeys fed similar diets. The guinea pigs fed the commercial diet had retinal and brain PUFA patterns similar to that produced by n−3 PUFA-deficient diets in rats and monkeys. Guinea pigs fed the canola oil diet had significantly greater retinal DHA levels than those fed the commercial diet, but lower than those fed fish oil. The data suggest that the guinea pig has a reduced capacity for DHA synthesis from α-linolenic acid as compared with other mammals. Supplementation of guinea pig diets with fish oil produced high retinal and brain DHA levels and prevented the accumulation of 22∶5n−6.     

Dietary linoleic, α-linolenic and oleic acids are oxidized at similar rates in rats fed a diet containing these acids in equal proportions

The objective of this study was to examine whether whole body oxidation rates of dietary linoleic, α-linolenic and oleic acids differ when the acids are provided in identical quantities. Male rats were fed for 10 wk a 15% fat (w/w) diet containing equal amounts of linoleic, α-linolenic and oleic acids (22.7, 23.0 and 23.2% of total fatty acids, respectively). At week 10, after overnight fasting, rats were intragastrically administered 20 μCi of either [1-¹⁴C]-labelled linoleic, α-linolenic or oleic acid in a 200-μL bolus of oil containing equal quantities of each fatty acid. The appearance of¹⁴CO₂ in expired air was then monitored hourly for 12h for each animal. A preliminary study had shown that growth and food consumption patterns in animals consuming the oil containing equal quantities of each of the fatty acids paralleled the patterns of animals that were self-selecting among separate diets, each of which contained one of the component oils. The appearance of¹⁴C, expressed as percent dose administered, peaked at 2–3 h post-dose for¹⁴C-labelled linoleic (5.28±0.37%/h), α-linolenic (6.92±0.51%/h) and oleic (5.98±0.44%/h) acids. Statistically these values were not significantly different. Cumulative¹⁴CO₂ excretion rates over 12 h were also similar for linoleic (27.2±0.9%), α-linolenic (26.8±1.2%) and oleic (25.9±1.2%) acids. The results suggest that the rat's capacity to oxidize 18-carbon unsaturated fatty acids is not affected by fatty acid unsaturation when these fatty acids are provided at equal dietary levels.     

Inhibition of desaturation of stearic acid in livers of rats fed ethionine

The effect of ethionine on the conversion of stearic acid to oleic acid was studied. Rats were fed essential fatty acid (EFA) deficient diet for three weeks, after which time half the animals were fed 0.25% DL-ethionine for nine additional days. Seventeen hours prior to killing, they were fed a slurry of the diet containing 18-¹⁴C-stearic acid. Liver triglycerides and phospholipids were extracted and separated and their fatty acid composition and the distribution of radioactivity between stearic and oleic acid was determined. In the tissues studied, oleic acid was maintained at control levels in ethionine-fed rats, but eicosatrienoic acid was significantly depressed. Distribution of radioactivity and specific activity of oleic acid in the triglycerides and phospholipids were significantly reduced by the analogue. In vitro studies of desaturation and chain elongation reactions, with liver microsomes, using 18-¹⁴C-stearic and 1-¹⁴C-linoleic acids as substrates, showed that ethionine depressed the synthesis of oleic acid from stearic and γ-linolenic from linoleic acid. Elongation of linoleic adie to a 20∶2 fatty acid was unaffected by ethionine. Therefore, the results showed that ethionine inhibited desaturation of stearic to oleic acid in vivo and in vitro and probably also impaired the desaturation of oleic to octadeca-6, 9-dienoic acid. Maintenance of control levels of oleic acid in the tissues of ethionine-fed, EFA deficient rats suggested the presence of synthetic pathways for oleic acid other than via desaturation of stearic acid. Presented in part at the AOCS Meeting, San Francisco, April 1969.     

The ratio of n-6 to n-3 polyunsaturated fatty acids in the rat diet alters serum lipid levels and lymphocyte functions

Previous studies have reported that feeding rats diets rich in fish oils, which contain high proportions of the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic and docosahexaenoic acids, results in lowering of blood lipid levels and suppression of lymphocyte functions testedex vivo andin vivo. The effects of other n-3 PUFA, such as α-linolenic acid, which is found in high proportions in linseed oil, are not as well documented. Therefore, in the present study, weanling male rats were fed for six weeks on one of five high-fat (20% by weight) diets made by mixing together sunflower and linseed oils; the resulting blends had n-6/n-3 PUFA ratios of 112.5:1 (pure sunflower oil), 14.8:1, 6.5:1, 0.8:1, and 0.33:1 (pure linseed oil); the levels of all other components in the diet were identical. The final body weight and total dissectable fat were lowest in rats fed the pure linseed oil diet. Serum cholesterol, triacylglycerol and nonesterified fatty acid concentrations decreased as the n-6/n-3 PUFA ratio of the diet decreased. The fatty acid composition of the serum and of spleen lymphocytes was influenced by the diet fed-there was a progressive decrease in the proportions of linoleic and arachidonic acids and a progressive increase in the proportion of α-linolenic acid as the n-6/n-3 PUFA ratio of the diet decreased. Eicosapentaenoic and docosahexaenoic acids were detected in the serum but not in spleen lymphocytes. Inclusion of α-linolenic acid in the diet resulted in significant suppression of spleen lymphocyte proliferation in response to the T-cell mitogen concanavalin A and in spleen lymphocyte natural killer cell activity, both measuredex vivo. The localized graft vs. host response, a measure of cellmediated immunityin vivo, progressively decreased as the n-6/n-3 PUFA ratio of the diet decreased. Thus, this study shows that dietary α-linolenic acid results in lowered blood lipid levels and suppressed lymphocyte functionsex vivo andin vivo. With respect to these effects, α-linolenic acid is as potent as dietary fish oil.     

Levels of polyunsaturated fatty acids in tissues from zinc-deficient rats fed a linseed oil diet

The effect of zinc deficiency on the levels of n−6 and n−3 polyunsaturated fatty acids (PUFA) in lipids from tissues of rats fed a diet containing linseed oil was investigated. Rats were fed either a control diet (25 mg Zn/kg) or a zinc-deficient diet (0.8 mg Zn/kg) for 10 d. To avoid energy and nutrient deficiency, 11.6 g of diet per day was administered by gastric tube. At the end of the experiment, rats fed the zinc-deficient diet had drastically reduced plasma zinc concentration and alkaline phosphatase activity consistent with severe zinc deficiency in these rats. Zinc-deficient rats had higher levels of n−3 PUFA, in particular eicosapentaenoic acid (EPA), and lower levels of n−6 PUFA, in particular linoleic acid, in liver and plasma phosphatidylcholine (PC) and in erythrocyte membrane total lipids than did control rats. By contrast, the levels of n−3 PUFA in PC from testes and heart, and in phosphatidylethanolamine (PE) from liver, testes and heart, were only slightly different between zinc-deficient and control rats. The study suggests that desaturation of α-linolenic acid is not inhibited by zinc deficiency, and that in zinc-deficient rats, n−3 PUFA preferentially incorporated into phospholipids at the expense of n−6 PUFA, especially EPA into PC. The study also shows that the effect of zinc deficiency on PUFA levels is different for PC and PE in rat tissues.     

Increased α-linolenic acid intake increases tissue α-linolenic acid content and apparent oxidation with little effect on tissue docosahexaenoic acid in the guinea pig

The essential fatty acids do not have identical roles in nutrition. Linoleic acid (LA) accumulates throughout the body of most mammals, whereas α-linolenic acid (ALA) is rarely found in tissue lipids to the same extent as LA. It has been argued that this is the result of metabolism of ALA to docosahexaenoic acid (DHA) or that ALA is rapidly β-oxidized to acetyl CoA and CO₂. In this study, we consider the effect of high and low ALA levels on the tissue distribution of ALA and other n-3 polyunsaturated fatty acids (PUFA) in all tissues. Guinea pigs were fed one of two defined diets for 3 wk from wearning with both diets containing 1.8% (by weight) of LA and either 1.7% ALA or 0.03% ALA. The high ALA diet was associated with significantly increased ALA levels in all tissues except the brain and significantly increased levels of long-chain n-3 PUFA in all tissues except intestines, brain, carcass, and skin. The long-chain n-3 PUFA content of the whole body was less than 5% of that of the ALA content in both diet groups, and the major long-chain n-3 PUFA (>66% of total) in the body was 22∶5n−3. The brain was the only tissue where the DHA content exceeded that of 22∶5n−3. On the low ALA diet, there appeared to be conservation of ALA based on a comparison of the ratio of LA to ALA in the tissues compared with that in the diet. On the high ALA diet there was a loss of ALA relative to LA in the tissues compared with the diet. These studies suggest that the low levels of tissue ALA in the guinea pig are likely the result of β-oxidation or excretion via the skin and fur rather than metabolism to DHA.     

Comparative study of the blood pressure effects of four different vegetable fats on young,spontaneously hypertensive rats

Following the suckling period, four groups of male four-week-old spontaneously hypertensive rats (SHR) were fed semisynthetic diets with 14% (by weight) of either sunflower seed oil [46% 18∶2(n−6); linoleic acid (LA)-rich], linseed oil [62.5% 18∶3(n−3)+12.9% 18∶2(n−6); α-linolenic acid (LNA)-rich], evening primrose oil [9.2% 18∶3(n−6)+71% 18∶2(n−6); γ-linolenic acid (LNA)-rich] or hydrogenated palm kernel fat [1.5% 18∶2(n−6); polyunsaturated fatty acid (PUFA)-deficient], respectively, up to an age of 18 wk. All diets enriched with PUFA provoked an attenuation of hypertension development. The effect was lowest in the LA-rich group and highest in the γ-LNA-rich group. Differences in fatty acid composition of renal phospholipids between groups reflect the fatty acids present in the respective dietary fats. Renomedullary production of PGF_2α was significantly reduced in α-LNA-rich and slightly diminished in γ-LNA-rich fed rats. Aortic formation of 6-keto-PGF_1α and TXB₂ was increased in animals fed the γ-LNA-rich diet. Thus, the attenuation of hypertension development cannot be explained only by changes in prostanoid formation. Other mechanisms possibly involved should be pursued.     

Biosynthesis of unsaturated fatty acids in the diatomPhaeodactylum tricornutum

The biosynthesis of fatty acids in the diatomPhaeodactylum tricornutum was studied. The diatom was incubated with sodium [1¹⁴C] acetate and the acids [1-¹⁴C] palmitic, [1-¹⁴C] stearic, [1-¹⁴C] linoleic and [1-¹⁴C] α-linolenic. The distribution of radioactivity in the products was determined by gas liquid radiochromatography. The diatom synthesized “de novo” not only saturated and monounsaturated fatty acids, but also linoleic, α-linolenic and other fatty acids including the highly polyunsaturated 20∶5ω3 and 22∶6ω3. When labeled acetate, stearic, α-linolenic or even linoleic acid were incubated with the diatom, the polyunsaturated C₂₀ fatty acids synthesized belonged predominantly to the ω 3 family. The existence of Δ9, Δ6, Δ5, Δ4, ω6 and possibly ω3 desaturases inP. tricornutum is suggested. Member of the Carrera del Investigador Científico of the Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Member of the Carrera del Investigador Cientifico of the Consejo Nacional de Investigaciones Cientificas y Técnicas.     

Age-related changes in Δ6 and Δ5 desaturase activities in rat liver microsomes

Age-related changes in Δ6 desaturation of [1-¹⁴C]α-linolenic acid and [1-¹⁴C]linoleic acid and in Δ5 desaturation of [2-¹⁴C]dihomo-γ-linolenic acid were studied in liver microsomes from Wistar male rats at various ages ranging from 1.5 to 24 mon. Desaturase activities were expressed both as specific activity of liver microsomes and as the capacity of whole liver to desaturate by taking into account the total amount of liver microsomal protein. Δ6 Desaturation of α-linolenic acid increased from 1.5 to 3 mon and then decreased linearly up to 24 mon to reach the same desaturation capacity of liver measured at 1.5 mon. The capacity of liver to desaturate linoleic acid increased up to 6 mon and then remained constant, whereas microsomal specific activity was equal at 1.5 and 24 mon of age. The capacity of liver to convert dihomo-γ-linolenic acid to arachidonic acid by Δ5 desaturation decreased markedly from 1.5 to 3 mon. It then increased to reach, at 24 mon, the same level as that observed at 1.5 mon. Age-related changes in the fatty acid composition of liver microsomal phospholipids at the seven time points studied and of erythrocyte lipids at 1.5 and 24 mon were consistent with the variations in desaturation capacity of liver. In particular, arachidonic acid content in old rats was slightly higher than in young rats whereas contents in linoleic and docosahexaenoic acids varied little throughout the life span. The results suggest that, in liver, the activity of desaturases may be regulated in the course of aging to maintain a constant level of polyunsaturated fatty acids in cellular membranes.     

Linoleic acid uptake by isolated enterocytes: Influence of α-linolenic acid on absorption

In a previous study we showed that intestinal uptake of α-linolenic acid (18∶3n−3) was carrier-mediated and we suggested that a plasma membrane fatty acid protein was involved in the transport of long-chain fatty acids. To further test this hypothesis, the mechanism of linoleic acid (18∶2n−6) uptake by isolated intestinal cells was examined using a rapid filtration method and 20 mM sodium taurocholate as solubilizing agent. Under these experimental conditions transport of [1-¹⁴C]linoleic acid monomers in the concentration range of 2 to 2220 nM was saturable with a V_m of 5.1±0.6 nmol/mg protein/min and a K_m of 183±7 nM. Experiments carried out in the presence of metabolic inhibitors, such as 2,4-dinitrophenol and antimycin A, suggested that an active, carriermediated mechanism was involved in the intestinal uptake of this essential fatty acid. The addition of excess unlabeled linoleic acid to the incubation medium led to a 89% decrease in the uptake of [1-¹⁴C]linoleic acid, whiled-glucose did not compete for transport into the cell. Other long-chain polyunsaturated fatty acids added to the incubation mixture inhibited linoleic acid uptake by more than 80%. The presence of α-linolenic acid (18∶3n−3) in the incubation medium caused the competitive inhibition (K_i=353 nM) of linoleic acid uptake. The data are compatible with the hypothesis that intestinal uptake of both linoleic, and α-linolenic acid is mediated by a membrane carrier common to long-chain fatty acids.     

The Production of Conjugated α-Linolenic, γ-Linolenic and Stearidonic Acids by Strains of Bifidobacteria and Propionibacteria

Conjugated fatty acids are regularly found in nature and have a history of biogenic activity in animals and humans. A number of these conjugated fatty acids are microbially produced and have been associated with potent anti-carcinogenic, anti-adipogenic, anti-atherosclerotic and anti-diabetogenic activities. Therefore, the identification of novel conjugated fatty acids is highly desirable. In this study, strains of bifidobacteria and propionibacteria previously shown by us and others to display linoleic acid isomerase activity were assessed for their ability to conjugate a range of other unsaturated fatty acids during fermentation. Only four, linoleic, α-linolenic, γ-linolenic and stearidonic acids, were converted to their respective conjugated isomers, conjugated linoleic acid (CLA), conjugated α-linolenic acid (CLNA), conjugated γ-linolenic acid (CGLA) and conjugated stearidonic acid (CSA), each of which contained a conjugated double bond at the 9,11 position. Of the strains assayed, Bifidobacterium breve DPC6330 proved the most effective conjugated fatty acid producer, bio-converting 70% of the linoleic acid to CLA, 90% of the α-linolenic acid to CLNA, 17% of the γ-linolenic acid to CGLA, and 28% of the stearidonic acid to CSA at a substrate concentration of 0.3 mg mL⁻¹. In conclusion, strains of bifidobacteria and propionibacteria can bio-convert linoleic, α-linolenic, γ-linolenic and stearidonic acids to their conjugated isomers via the activity of the enzyme linoleic acid isomerase. These conjugated fatty acids may offer the combined health promoting properties of conjugated fatty acids such as CLA and CLNA, along with those of the unsaturated fatty acids from which they are formed.     

Effects of dietary polyunsaturated fatty acids on neuronal function

Diets deficient in linoleic acid (18∶2n−6), or that have unusual ratios of linoleic acid to α-linolenic acid (18∶3n−3) induce changes in the polyunsaturated fatty acid (PUFA) composition of neuronal and glial membranes. Such changes have been linked to alterations in retina and brain function. These functional effects are presumed to follow from the biochemical consequences of modifying membrane PUFA content; known effects include modifications in membrane fludity, in the activities of membrane-associated, functional proteins (transporters, receptors, enzymes), and in the production of important signaling molecules from oxygenated linoleic and α-linolenic acid derivatives. However, despite the demonstration that central nervous system function changes when dietary PUFA intake is altered, and that in general, membrane PUFA content influences membrane functions, little work has focused specifically on brain and retina to reveal the underlying biochemical bases for such effects. This review examines this issue, looking at known effects of dietary PUFA on neurons in both the central and peripheral nervous systems, and attempts to identify some approaches that might promote productive investigation into the underlying mechanisms relating changes in dietary PUFA intake to alterations in neuronal and overall nervous system functioning.     

Dietary fish oil inhibits Δ6-desaturase activity in vivo

Liver Δ6-desaturase activity was determined in mice which were made deficient in (i) n-6 and n-3 polyunsaturated fatty acids (PUFA), (ii) n-6 PUFA, or (iii) arachidonic acid (AA). Initially, the mice were subjected to two cycles of a fasting (1 d)/refeeding (2–3 d) protocol in which they were refed an essential fatty acid-deficient (EFAD) diet during the refeeding period. This 1-wk fasting/refeeding protocol, referred to as F/R EFAD, produced a rapid and substantial decline in tissue n-3 and n-6 PUFA and a corresponding increase in n-9 fatty acids, notably oleic acid and Mead acid (20:3n-9). Combined liver Δ6-desaturase/elongase/Δ5-desaturase activities in vivo were quantified by measuring the conversion of ¹⁴C-linoleic acid (LA) to ¹⁴C-AA in mouse liver. Although F/R EFAD caused, as expected, a substantial decline in liver AA and LA content, the conversion of ¹⁴C-LA to ¹⁴C-AA was the same in these mice as in chow-fed controls (approximately 33–34%). Subsequent refeeding of F/R EFAD mice with an EFAD diet, supplemented with corn oil, restored tissue n-6 PUFA levels without altering the conversion of ¹⁴C-LA to ¹⁴C-AA. In contrast, refeeding with an EFAD diet, supplemented with fish oil, inhibited ¹⁴C-LA to ¹⁴C-AA conversion by 78%. Significantly, inhibition of conversion of ¹⁴C-LA to ¹⁴C-AA was maintained in F/R EFAD mice that were subsequently fed an EFAD diet supplemented with a 1:1 mixture of fish oil/corn oil. This latter protocol yielded a unique liver fatty acid composition in which AA was selectively depleted, whereas LA and the n-3 PUFA were increased. The data suggest that dietary n-3 C_20–22 PUFA negatively regulate the in vivo synthesis of n-6 PUFA at the level of the Δ6-desaturase.     

Effect of epinephrine on the oxidative desaturation of fatty acids in the rat adrenal gland

Delta-6 and Δ5 desaturation activity of rat adrenal gland microsomes was studied to determine the effect of microsomal protein and the substrate saturation curves. This tissue has a very active Δ6 desaturase for linoleic and α-linoleic acids and a Δ5 desaturase for eicosa-8,11,14-trienoic acid. The administration of epinephrine (1 mg/kg body weight) 12 hr before killing, produced approximately a 50% decrease in desaturation of [1-¹⁴C]linoleic acid to γ-linolenic acid, [1-¹⁴C]α-linolenic acid to octadeca-6,9,12,15-tetraenoic acid and [1-¹⁴C]eicosa-8,11,14-trienoic acid to arachidonic acid. A 30% decrease in Δ5 desaturation activity was also shown after 7 hr of epinephrine treatment. The changes on the oxidative desaturation of the same fatty acids in liver microsomes were similar. No changes were observed in the total fatty acid composition of adrenal microsomes 12 hr after epinephrine treatment. Mechanisms of action of the hormone on the biosynthesis of polyunsaturated fatty acids in the adrenal gland are discussed.