The metabolism of 1-14C arachidonic acid in pyridoxine-deficient and pair-fed control rats

The metabolism of 1-¹⁴C arachidonate was studied in pyridoxine-deficient and pair-fed pyridoxine-supplemented control rats. The studies included intestinal absorption, oxidation to¹⁴CO₂, organ uptakes and distribution of¹⁴C in the fatty acids of the various organs. Generally, pyridoxine deficiency resulted in little or no alteration of the metabolism of arachidonic acid 6 and 12 hrs after oral administration. A notable exception occurred in hearts of deficient animals in which the proportion of the incorporated¹⁴C activity found in fatty acids other than 20:4 was larger than that observed in hearts of pyridoxine-supplemented animals. A significant amount of¹⁴C activity in a water-soluble form was observed in hydrolysates of intestinal contents and of intestines of both groups. Pyridoxine-deficient rats had larger quantities than their respective pair-fed pyridoxine-supplemented controls. Most of the¹⁴C activity of fatty acids of various organs was present as arachidonic acid, but significant activity was present both in fatty acids of shorter and of longer retention time than 20:4. In brain about 20% of the¹⁴C activity in fatty acids was in a fraction tentatively identified as an 18:2 isomer. In lungs about 10% of the¹⁴C activity was in a fraction tentatively identified as a 22:2 isomer and a similar quantity was observed in a polyene tentatively identified as a 22:4.     

Modulation of adjuvant-induced arthritis by dietary arachidonic acid in essential fatty acid-deficient rats

Controlled feeding of linoleic acid (LA) or arachidonic acid (AA) to essential fatty acid-deficient (EFAD) rats was used to define the relationship between dietary AA and the inflammatory response evoked during adjuvant-induced arthritis. Based on energy percentage, EFAD rats were fed AA at the human daily equivalent (1×; 5.5 mg/day) or 10 times that amount (10×; 55 mg/day) or, alternatively, 0.5× of LA (273 mg/day). Feeding of 0.5×LA restored the plasma level of AA to that in chow-fed controls. In contrast, feeding of 1×AA only partially restored the plasma level of AA; 10×AA was required to fully replete AA. In parallel to the degree of repletion of AA in plasma, there were accompanying decreases in the levels of palmitoleic acid, oleic acid, and Mead acid. Compared to rats fed the standard laboratory chow diet (Control), edema in the primary hind footpads was decreased by 87% in EFAD, 71% in EFAD+1×AA, 45% in EFAD+10×AA, and 30% in EFAD+0.5×LA. The decrease in edema in the footpads of EFAD rats was nearly identical to the decrease in edema in the footpads of Control rats dosed with indomethacin. Hind footpad edema correlated with the final AA plasma level and eicosanoid levels extracted from hind footpad tissue, but not with neutrophil infiltration. The data showed that 0.5×LA and 10×AA, but not 1×AA, could quickly replete AA, accompanied by the synthesis of AA-derived eicosanoids and restoration of edema. These results suggest that in humans consumption of the average daily amount of AA without concurrent ingestion of LA would not alleviate an EFAD state.     

Dietary arachidonic acid reduces fatty liver,increases diet consumption and weight gain in ethanol-fed rats

We fed young male Sprague-Dawley rats for 4 wk ad libitum liquid diets containing 34% of the calories as ethanol and 35% as fat with (AA+) and without (AA−) arachidonic acid (20∶4). Additional rats in the control groups were fed similar diets made isocaloric with dextrose with (CA+) and without (CA−) 20∶4. The liver triglyceride (TG) content of rats in the AA+ group was reduced ca. 3-fold over that of rats in the AA-group. The diet consumption and body wts of rats in the AA+ group were significantly greater than those of rats fed alcohol without the 20∶4 supplement (AA−). Also livers from rats in the AA+ group were as large as those from rats in control groups (CA+, CA−) and ca. twice as large as those from rats in the AA-group. The fatty acid composition of liver TG in rats fed the alcohol diet was similar to that of dietary fat. Levels of 20∶4 and docosatetraenoic acid (22∶4) in liver TG fatty acids from rats fed diets without arachidonate (AA−, CA−) were low (trace to 1.6%). After ingestion of arachidonic acid, 20∶4 increased to ca. 10% and 22∶4 to ca. 5%. The content of liver phospholipids was higher in livers of rats fed ethanol (AA−) than in those of controls (CA−). Presented at the ISF/AOCS World Congress, April 27-May 1, 1980, New York City.     

The effect of dietary arachidonic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans

Arachidonic acid (AA) is the precursor of thromboxane and prostacyclin, two of the most active compounds related to platelet function. The effect of dietary AA on platelet function in humans is not understood although a previous study suggested dietary AA might have adverse physiological consequences on platelet function. Here normal healthy male volunteers (n=10) were fed diets containing 1.7 g/d of AA for 50 d. The control diet contained 210 mg/d of AA. Platelet aggregation in the platelet-rich plasma was determined using ADP, collagen, and AA. No statistical differences could be detected between the aggregation before and after consuming the high-AA diet. The prothrombin time, partial thromboplastin time, and the antithrombin III levels in the subjects were determined also. There were no statistically significant differences in these three parameters when the values were compared before and after they consumed the high-AA diet. The in vivo bleeding times also did not show a significant difference before and after the subjects consumed the high-AA diet. Platelets exhibited only small changes in their AA content during the AA feeding period. The results from this study on blood clotting parameters and in vitro platelet aggregation suggest that adding 1.5 g/d of dietary AA for 50 d to a typical Western diet containing about 200 mg of AA produces no observable physiological changes in blood coagulation and thrombotic tendencies in healthy, adult males compared to the unsupplemented diet. Thus, moderate intakes of foods high in AA have few effects on blood coagulation, platelet function, or platelet fatty acid composition.     

Effect of dietary fatty acids on Δ5 desaturase activity and biosynthesis of arachidonic acid in rat liver microsomes

The effect of different fatty acids supplemented to a fat-free diet on the activity of Δ5 desaturase was studied. Fat-free diet produces a reduction in the conversion of eicosa-8,11,14-trienoic acid to arachidonic acid. The addition of thecis-ω6 acids, linoleic, γ-linolenic or arachidonic to the diet produces an increase of eicosatrienoic acid desaturation, shifting Δ5 desaturase activity towards the controls on a balanced diet. This reactivation is apparently produced by induction of enzyme biosynthesis since linoleate effect was suppressed by simultaneous cycloheximide injection. On the contrary, no changes in Δ5 desaturation activity were found when the diet was supplemented with palmitic or 9-trans,12-trans-linoleic acid. The changes on the activity of Δ5 desaturase were compared with the fatty acid composition of plasma and liver microsomes.     

The effect of dietary arachidonic acid on plasma lipoprotein distributions, apoproteins, blood lipid levels, and tissue fatty acid composition in humans

Normal healthy male volunteers (n=10) were fed diets (high-AA) containing 1.7 g/d of arachidonic acid (AA) for 50 d. The control (low-AA) diet contained 210 mg/d of AA. Dietary AA had no statistically significant effect on the blood cholesterol levels, lipoprotein distribution, or apoprotein levels. Adipose tissue fatty acid composition was not influenced by AA feeding. The plasma total fatty acid composition was markedly enriched in AA after 50 d (P<0.005). The fatty acid composition of plasma lipid fractions, cholesterol esters, triglycerides, free fatty acids, and phospholipid (PL) showed marked differences in the degree of enrichment in AA. The PL plasma fraction from the subjects consuming the low-AA diet contained 10.3% AA while the subjects who consumed the high-AA diet had plasma PL fractions containing 19.0% AA. The level of 22:4n-6 also was different (0.67 to 1.06%) in the plasma PL fraction after 50 d of AA feeding. After consuming the high-AA diet, the total red blood cell fatty acid composition was significantly enriched in AA which mainly replaced linoleic acid. These results indicate that dietary AA is incorporated into tissue lipids, but selectively into different tissues and lipid classes. Perhaps more importantly, the results demonstrate that dietary AA does not alter blood lipids or lipoprotein levels or have obvious adverse health effects at this level and duration of feeding.     

Severe fatty liver in rats fed a fat-free ethanol diet,and its prevention by small amounts of dietary arachidonate

Rats were fed ethanol and a fat-free diet for 30 days to determine whether dietary fat is needed for the development of fatty liver. The severity of fatty liver was similar to that of rats fed an isocaloric diet with 35% fat. Small amounts (29 mg/day) of dietary arachidonic acid prevented alcoholic fatty liver. Rats fed either the alcohol (AF) or control (CF) fat-free diets developed essential fatty acid deficiency (EFAD) as measured by the triene/tetraene ratio of liver and plasma lipids. Rats fed arachidonic acid (AA, alcohol and CA, control diets) did not develop EFAD. Although EFAD alone did not cause the development of fatty liver, the combination of dietary ethanol and EFAD did. The ratios of 16∶1/16∶0 and 18∶1/18∶0 in liver lipids indicated that desaturase enzymes were less active and lipogenesis was reduced in rats fed the AA diet compared to those fed the AF diet. In contrast, stimulated lipogenesis appears to have been the cause of fatty liver in rats fed the AF diet. Presented at the XII International Congress of Nutrition, San Diego, CA, August 1981. Abbreviations: Diets are indicated as fat-free with ethanol (AF), fat-free without ethanol (CF), or similar diets with 0.9% of the calories as arachidonic acid with (AA) or without (CA) ethanol. The composition of these diets is discribed in the text and Table 1.     

Dietary arachidonic acid and hepatic desaturation of fatty acids in obese zucker rats

The effect of low levels of dietary arachidonic acid (20:4n-6) on Δ6 desaturation of linoleic acid (18:2n-6) and α-linolenic acid (18:3n-3), and on Δ5 desaturation of dihomo-γ-linolenic acid (20:3n-6) were studied in liver microsomes of obese Zucker rats, in comparison with their lean littermates. Fatty acid composition of serum total lipids and of phospholipids from liver microsomes and from total heart and kidney was determined to see whether modifications of desaturation rate, if any, were reflected in the tissue fatty acid profiles. Animals fed for 12 wk on a balanced diet, containing 20:4n-6 and 18:2n-6, were compared to those fed 18:2n-6 only. The low amount of dietary 20:4n-6 greatly inhibited Δ6 desaturation of 18:2n-6 and Δ5 desaturation of 20:3n-6, whereas Δ6 desaturation of 18:3n-3 was slightly increased in obese rats. Inhibition of the biosynthesis of long-chain n-6 fatty acids by dietary arachidonic acid was only slightly reflected in the 20:4n-6 content of liver microsome phospholipids. On the contrary, the enrichment of serum total lipids and heart and kidney phospholipids in this fatty acid was pronounced, more in obese than in lean animals. Our results show that, although the desaturation rate of the n-6 fatty acids in liver microsomes was greatly decreased by the presence of arachidonic acid in the diet, the tissue phospholipid content in arachidonic acid was not depressed. The potentiality of synthesis of eicosanoids of the 2 family from this fatty acid is consequently not lower, especially in obese rats, in which certain tissues are deficient in arachidonic acid, in comparison with their lean littermates.     

The effect of dietary erucic acid on cardiac triglycerides and free fatty acid levels in rats

Male Sprague-Dawley rats, 3 weeks of age, were fed semisynthetic diets containing test oils at 20% by weight for 3 days, 1 week, and 16 weeks. The test oils contained up to 22.3% erucic acid. Growth retardation was evident in rats fed rapeseed oil high in erucic acid, and soybean oil and Tower rapeseed oil diets containing about 5% erucic acid. Cardiac triglyceride accumulation was found in rats fed diets containing about 5% erucic acid but not in rats fed Tower rapeseed oil which contains 0.2% of this acid. The cardiac free fatty acid levels were low, 50–100 μg/g of wet heart tissue, and were not affected by feeding diets containing about 5% erucic acid. Feeding a diet containing a high erucic acid rapeseed oil did result in higher free fatty acid levels but only at 3 days and 1 week; the level at 16 weeks was similar to the other oils. The fatty acid analysis of cardiac triglycerides and free fatty acids showed high percentages of erucic acid at 3 days and 1 week; at 16 weeks these levels had declined significantly. The results indicate that the accumulated erucic and eicosenoic acids, at 3 days and 1 week, accounted for the increase in cardiac free fatty acids when rats were fed the high erucic acid rapeseed oil. There appears to be no evidence that the early cardiac triglyceride or free fatty acid accumulation is related to the formation of the long term myocardial lesions. Contribution No. 739 Animal Research Institute.     

In vivo incorporation of3H arachidonic acid and14C linoleic acid into liver lipids from essential fatty acid-deficient rats

Essential fatty acid (EFA)-deficient rats were injected intraportally with a labeled solution containing³H arachidonic acid and¹⁴C-linoleic acid during a 1 min period. Livers were quickly frozen, pulverized, and the lipids extracted and fractioned by thin layer chromatography. The incorporation of³H and¹⁴C into liver lipids was measured, and the per cent distribution of radioactivity into the different lipid fractions determined and compared with those previously obtained from normal rats. In contrast with normal rats, ca. 70% of the³H arachidonic acid and¹⁴C-linoleic acid incorporated into total lipids from EFA-deficient rats was recovered in the phospholipid fraction. From the results of this experiment, it is suggested that a more active deacylation-reacylation cycle in EFA-deficiency could be responsible for this increase.     

High levels of dietary arachidonic acid triglyceride exhibit no subchronic toxicity in rats

Arachidonic acid (AA), an n?6 long-chain polyunsaturated fatty acid (LC-PUFA), serves an important role in the body as a structural fatty acid of many tissues including neurological tissues. It is also a precursor of the n?6 class of eicosanoids and is the most abundant n?6 LC-PUFA found in human breast milk. We have optimized the production of a microfungal source of a triglyceride oil (ARASCO^®) which is enriched in AA to about 40% by weight. To establish the safety of this oil as a food, we evaluated the effect of ARASCO^® in Sprague-Dawley rats (20/sex/group) gavaged at dose levels of 1.0 and 2.5 g/kg/d for a period of 90 d, paying special attention to any potential neurotoxicity of the oil. Two groups of control animals received either untreated standard laboratory diet (untreated control) or the same diet and vehicle oil at the same dose volume administered to the treated animals (vehicle control). Physical observations, ophthalmoscopic examinations, body weight, food consumption, clinical chemistry, hematology parameters, neurobehavioral assessments, and macroscopic as well as microscopic postmortem evaluations were performed. Tissue fatty acid analyses indicated that the AA levels in the brain, heart, and liver of the high-dose ARASCO^®-fed animals increased by 8, 59, and 76%, respectively, indicating that the AA in the oil was readily incorporated into tissue lipids. In spite of this high elevation in tissue AA levels, no developmental, histopathological, or neuropathological differences were seen in the animals administered ARASCO^® compared with the vehicle control animals. Being highly enriched in AA, ARASCO^® offers the means to study the effect of this fatty acid in experimental settings and in human metabolic studies.     

The influence of dietary nucleotides and long-chain polyunsaturated fatty acids on the incorporation of [3H] arachidonic acid on experimental liver cirrhosis

The purposes of this study were to determine: a) the incorporation of labeled [3H] arachidonic acid on the intestinal mucosa, the liver and plasma, after 1,3 and 5 hours of administration, b) preferential incorporation by different tissues, c) and the effects on experimental rats with thioacetamide-induced cirrhosis, after four weeks of a dietary supplementation with nucleotides and long-chain polyunsaturated fatty acids. 209 female Wistar rats were divided into two groups (control and TAA group). The TAA group was given 300 mg of thioacetamide/L, in their drinking water for four months. After this period, a sample of 6 rats were taken from each group and examined, to evaluate the biochemical and histological changes of the experimental model, and 36 rats were taken to determine the incorporation of radioactivity by the groups. The rest of the animals were divided into four subgroups. Each group, receiving a supplementary diet with only long-chain polyunsaturated fatty acids and/or nucleotides or neither, for 4 weeks. After four months of thioacetamide, the incorporation of the [3H] arachidonic acid showed: a) an increased within 3 h in the intestinal mucosa, b) a decreased in the liver after 3 to 5 h c) and a drastic decrease in the plasma after 3 to 5 h. With a dietary supplementation of long-chain polyunsaturated fatty acids and nucleotides combined, there was a decrease of accumulate [3H] arachidonic acid in the intestine and a increase in the liver and plasma. The simultaneous supply of dietary polyunsaturated fatty acids and nucleotides was beneficial in the reversal of abnormalities of the lipid metabolism, in this experimental model of liver cirrhosis.     

The effect of dietary fatty acid balance on myocardial lesions in male rats

Three hundred (experiment I) and 350 (experiment II) weanling, 3-week-old male Sprague-Dawley rats weighing between 40–50 g were randomly assigned two per cage and 50 per dietary treatment to study the effect of dietary fatty acid balance on myocardial lesions. The following oils were tested: Experiment I.Brassica napus var. Tower rapeseed oil [Tower RSO, 1974 cultivar and 1975 cultivar, each containing 0.3% erucic (22∶1) acid];B. napus var. Zephyr RSO containing 0.9% 22∶1; corn oil; olive oil; and soybean oil. Experiment II.B. napus var. Tower RSO (1974 cultivar), olive oil, soybean oil, and the following oils to which was added the indicated level of free 22∶1; Tower +0.5% 22∶1; Tower +5.6% 22∶1; olive oil +4.4% 22∶1; soybean oil +5.7% 22∶1. In each case the oils were incorporated in a semisynthetic diet at a level of 20% by weight. Heart and heart lipid weights of rats fed the different oils did not differ statistically from each other. Fatty acid analyses of heart lipids revealed that the fatty acid composition of the cardiac lipids reflected that of the diet fed. In experiment I, there was a definite but significantly lower incidence (P<0.01) and severity (P<0.01) of heart lesions in rats fed control oils (corn, olive, soybean) than in rats fed rapeseed oils. Also, in experiment II, a definite but lower incidence and severity of heart lesions occurred in rats fed control oils (soybean, olive) compared to rats fed Tower RSO or this oil with added free 22∶1. Adding 22∶1 to an oil naturally high in 18∶3 (soybean) did not alter the incidence of heart lesions, whereas adding 22∶1 to an oil naturally high in 18∶1 (olive) increased significantly (P<0.01) both the incidence and severity of heart lesions. Thus, it appears that the background incidence of heart lesions that are found in the rat in any case, and which are increased by rapeseed oil feeding, is caused by the imbalanced fatty acid composition of the oil for the growing rat, i.e. high monoenes (18∶1, 20∶1, and 22∶1) and high 18∶3 and is not only due to the presence of excess 18∶3. Contribution No. 706, Animal Research Institute.     

The effects of dietary cholesterol on blood and liver polyunsaturated fatty acids and on plasma cholesterol in rats fed various types of fatty acid diet

Male rats were fed on a fat-free diet for 8 weeks and then switched to diets containing 10% hydrogenated coconut oil (HCO), safflower oil (SFO) or evening primrose oil (EPO). Half of each group was also given 1% of cholesterol in the diet. After 5 further weeks, plama, red cell and liver fatty acids were measured in the various lipid fractions. Plasma and liver cholesterol also were estimated. In almost all fractions and on all three diets, feeding cholesterol led to accumulation of the substrates of desaturation reactions and to deficits of the products of these reactions. The results were consistent with inhibition of Δ-6, Δ-5 and Δ-4 desaturation of n−6 essential fatty acids. Since the diets were deficient in n−3 fatty acids, levels were very low but were also consistent with inhibition of desaturation. In contrast, cholesterol had relatively less consistent effects on 20∶3n−9, suggesting that desaturation of n−9 fatty acids was less inhibited. Plasma cholesterol levels rose sharply in the HCO and SFO groups but not at all in the EPO group. EPO contains the product of Δ-6 desaturation, 18∶3n−6, suggesting that conversion of linoleic acid to 18∶3n−6 and possibly to further metabolites may be important for the cholesterol-lowering effect of polyunsaturates.     

Effects of dietary vegetable oil on atlantic salmon hepatocyte fatty acid desaturation and liver fatty acid compositions

Fatty acyl desaturase activities, involved in the conversion of the C₁₈ EFA 18∶2n−6 and 18∶3n−3 to the highly unsaturated fatty acids (HUFA) 20∶4n−6, 20∶5n−3, and 22∶6n−3, are known to be under nutritional regulation. Specifically, the activity of the desaturation/elongation pathway is depressed when animals, including fish, are fed fish oils rich in n−3 HUFA compared to animals fed, vegetable oils rich in C₁₈ FFA. The primary aims of the present study were (i) to establish the relative importance of product inhibition (n−3 HUFA) vs. increased substrate concentration (C₁₈ EFA) and (ii) to determine whether 18∶2n−6 and 18∶3n−3 differ in their effects on the hepatic fatty acyl desaturation/elongation pathway in Atlantic salmon (Salmo salar). Smolts were fed 10 experimental diets containing blends of two vegetable oils, linseed (IO), and rapeseed oil (RO), and fish oil (FO) in a triangular mixture design for 50 wk. Fish were sampled after 32 and 50 wk, lipid and FA composition of liver determined, fatty acyl desaturation/elongation activity estimated in hepatocytes using [1-¹⁴C]18∶3n−3 as substrate, and the data subjected to regression analyses. Dietary 18∶2n−6 was positively correlated, and n−3 HUFA negatively correlated, with lipid content of liver. Dietary 20∶5n−3 and 22∶6n−3 were positively correlated with liver FA with a slope greater than unity suggesting relative retention and deposition of these HUFA. In contrast, dietary 18∶2n−6 and 18∶3n−3 were positively correlated with liver FA with a slope of less than unity suggesting metabolism via β-oxidation and/or desaturation/elongation. Consistent with this, fatty acyl desaturation/elongation in hepatocytes was significantly increased by feeding diets containing vegetable oils. Dietary 20∶5n−3 and 22∶6n−3 levels were negatively correlated with hepatocyte fatty acyl desaturation. At 32 wk, 18∶2n−6 but not 18∶3n−3 was positively correlated with hepatocyte fatty acyl desaturation, wheres the reverse was true at 50 wk. The data indicate that both feedback inhibition through increased n−3 HUFA and decreased C₁₈ fatty acyl substrate concentration are probably important in determining the level of hepatocyte fatty acyl desaturation and that 18∶2n−6 and 18∶3n−3 may differ in their effects on this pathway.     

Effect of degree of unsaturation in dietary fatty acids on arachidonic acid mobilization by peritoneal macrophages

Cells from rats fed with a tripalmitin diet showed a depletion of phospholipid arachidonate and n-3 fatty acids such as eicosapentaenoic and docosahexaenoic acids (EPA and DHA). In rats fed fish oil diet, a significant reduction in archidonic acid (AA) content was observed whereas EPA and DHA were incorporated into membranes lipids. These changes in lipid composition of membranes did not affect cellular adherence, phagocytic capability, or [³H]AA incorporation. However, both tripalmitin and fish oil diets induced a decrease in [³H]AA mobilization stimulated by 4β-phorbol-12-myristate 13-acetate, A23187, or opsonized-zymosan in rat peritoneal macrophages. These results demonstrate that the antiinflammatory effects of essential fatty acids deficiency or n-3 enrichment diets may be associated with a decreased AA mobilization in resident rat peritoneal macrophages treated with proinflammatory agents.     

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.     

Specific inhibition of hepatic fatty acid synthesis exerted by dietary linoleate and linolenate in essential fatty acid adequate rats

Dietary linoleate and linolenate were investigated for their ability to specifically inhibit liver and adipose tissue lipogenesis in meal-fed (access to food 900-1,200 hr), essential fatty acid (EFA) adequate rats. Supplementing a high carbohydrate diet containing 2.5% safflower oil with 3% palmitate 16∶0, oleate 18∶1, or linoleate 18∶2 did not affect in vivo liver or adipose tissue fatty acid synthesis. However, 18∶2 addition to the basal diet did result in a significant (P<0.05) decline of liver fatty acid synthetase (FAS) and glucose-6-phosphate dehydrogenase (G6PD) activities. When the safflower oil content of the basal diet was reduced to 1%, the addition of 3% 18∶2 or linolenate 18∶3 significantly (P<0.05) depressed hepatic FAS, G6PD, and in vivo fatty acid synthesis by 50%. Addition of 18∶1 caused no depression in hepatic FAS activity but did result in a significant (P<0.05) decline in liver G6PD activity and fatty acid synthesis which was intermediate between basal and basal +18∶2-or+18∶3-fed animals. Adipose tissue rates of lipogenesis were completely unaffected by dietary fatty acid supplementation. Similarly, the addition of 3 or 5% 18∶3 to a basal diet for only one meal resulted in no change in lipogenesis relative to that in animals fed the basal diet. The data indicate that, like rats fed EFA-deficient diets, dietary 18∶2 and 18∶3 exert a specific capacity to depress rat liver FAS and G6PD activities and rate of fatty acid synthesis. Michigan Agricultural Experiment station Journal Article No. 7581. D.R. Romsos is the recipient of Career Development Award K04 AM 00112     

Effects of age and dietary essential fatty acids on desaturase activities and on fatty acid composition of liver microsomal phospholipids of adult rats

The combined effects of age and dietary n−6 and n−3 fatty acids were studied in 3-, 6- and 9-month-old rats. At each age, two groups were fed diets containing 5% (w/w) of vegetable oils rich in either 18∶3n−6 (borage group) or 18∶3n−6 plus 18∶4n−3 (black currant group), for a period increasing with age. A control group was fed the essential fatty acids 18∶2n−6 and 18∶3n−3 only. For each group, Δ6, Δ5 and δ9 desaturase activities were measured in liver microsomes, and fatty acid composition was determined in microsomal phospholipids. Desaturase activity varied as a function of age and dietary lipids. Δ6 Desaturation of 18∶3n−3 was more sensitive to these factors while Δ6 desaturation of 18∶2n−6 and Δ9 desaturation were more dependent on season than the other two. Desaturase activity was influenced more by the black currant than by the borage diet, especially at 6 and 9 months of age. A large proportion of arachidonic acid was maintained in the microsomes independent of the diet. Changes in the fatty acid composition did not strictly reflect the differences in desaturase activities. The effects of the two factors (age and diet) on the activities of the desaturases are complex, suggesting that the enzymes are susceptible to other factors as well.