Dietary saturated fat level alters the competition between α-linolenic and linoleic acid

Male weanling rats were fed semi-synthetic diets high in saturated fat (beef tallow) vs high in linoleic acid (safflower oil) with or without high levels of α-linolenic acid (linseed oil) for a period of 28 days. The effect of feeding these diets on cholesterol content and fatty acid composition of serum and liver lipids was examined. Feeding linseed oil with beef tallow or safflower oil had no significant effect on serum levels of cholesterol. Serum cholesterol concentration was higher in animals fed the safflower oil diet than in animals fed the beef tallow diet without linseed oil. Feeding linseed oil lowered the cholesterol content in liver tissue for all dietary treatments tested. Consumption of linseed oil reduced the arachidonic acid content with concomitant increase in linoleic acid in serum and liver lipid fractions only when fed in combination with beef tallow, but not when fed with safflower oil. Similarly, ω3 fatty acids (18∶3ω3, 20∶5ω3, 22∶5ω3, 22∶6ω3) replaced ω6 fatty acids (20∶4ω6, 22∶4ω6) in serum and liver lipid fractions to a greater extent when linseed oil was fed with beef tallow than with safflower oil. The results suggest that the dietary ratio of linoleic acid to saturated fatty acids or of 18∶3ω3 to 18∶2ω6 may be important to determine the cholesterol and arachidonic acid lowering effect of dietary α-linolenic acid.     

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.     

Effects of diets high in saturated fat and cholesterol on the lipid composition of canine platelets

The phospholipid composition of platelets from dogs on various experimental diets was determined. Thyroidectomized foxhounds were fed a control diet or the control diet supplemented with (1) beef tallow, (2) beef tallow and cholesterol, or (3) beef tallow, cholesterol, and safflower oil for 23 weeks prior to isolation of platelets. Platelets from animals fed the control diet contained 36.7% phosphatidylcholine (PC), 22.8% phosphatidylethanolamine (PE), 18.4% sphingomyelin (Sph), 11.8% phosphatidylserine (PS), 6.3% phosphatidylinositol (PI), and 2.2% lysophosphatidylcholine. The PE was 77.6% in the plasmalogen form. No highly significant changes in the phospholipid class composition resulted from the experimental diets. Cholesterol supplementation of the diets, however, caused consistent alterations in the fatty acid compositions of the platelet phospholipids including increases in the percentages of 18∶1ω9 (oleic acid), 18∶2ω6 (linoleic acid), and 20∶3ω6 (homo-gamma linolenic acid) and a decrease in the percentage of 20∶4ω6 (arachidonic acid). Addition of safflower oil to the tallow-cholesterol diet partially reversed these effects. These cholesterol-induced alterations in fatty acid composition could be due to exchange with plasma lipids, de novo synthesis, or altered platelet metabolism. The mechanism remains to be determined. Der. Nelson’s current affiliation is the Lipid Metabolism Branch, Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute.     

Effect of dietary fat on diabetes-induced changes in liver microsomal fatty acid composition and glucose-6-phosphatase activity in rats

Experimental diabetes may manifest itself in a defect in liver microsomal fatty acid desaturation and increased activity of glucose-6-phosphatase (G-6-Pase). The present study was designed to determine whether these changes could be normalized by a change in the dietary fat consumed. Control and streptozotocin-induced diabetic rats were fed nutritionally adequate diets which varied in fatty acid composition. Fatty acid analysis of liver microsomal phospholipids revealed that non-diabetic control animals fed saturated fat (beef tallow) or a diet high in ω3 fatty acids (fish oil) exhibited a significantly higher level of 18∶2ω6 and a lower level of 20∶4ω6 in the phosphatidylcholine and phosphatidylethanolamine fractions compared with diabetic animals. Control and diabetic animals fed the high linoleic acid diet had similar levels of 18∶2ω6 in the microsomal phosphatidylcholine and phosphatidylserine fractions. Microsomal G-6-Pase activity was higher in diabetic than in control animals. Activity of G-6-Pase was lower in microsomes of control animals fed the soybean oil or the fish oil diet, but was not significantly reduced in diabetic animals fed high polyunsaturated fats. Blood glucose levels were similar in control groups fed the different diets, but the plasma hemoglobin A1c level was lower in diabetic animals fed the soybean oil diet. Cholesterol and triglyceride levels were lower in diabetic animals fed the fish oil-based diet. The results suggest that dietary fat manipulation has the potential to change at least some of the abnormalities in the microsomal membrane in experimental diabetes.     

Influence of dietary fat composition on intestinal absorption in the rat

Omega-3 fatty acids influence the function of the intestinal brush border membrane. For example, the omega-3 fatty acid eicosapentaenoic acid (20∶5ω3) has an antiabsorptive effect on jejunal uptake of glucose. This study was undertaken to determine whether the effect of feeding α-linolenic acid (18∶3ω3) or EPA plus docosahexaenoic acid (22∶6ω3) on intestinal absorption of nutrients was influenced by the major source of dietary lipid, hydrogenated beef tallow or safflower oil. Thein vitro intestinal uptake of glucose, fatty acids and cholesterol was examined in rats fed isocaloric diets for 2 weeks: beef tallow, beef tallow + linolenic acid, beef tallow + eicosapentaenoic acid/docosahexaenoic acid, safflower oil, safflower oil + linolenic acid, or safflower oil + eicosapentaenic acid/docosahexaenoic acid. Eicosapentaenoic acid/docosahexaenoic acid reduced jejunal uptake of 10 and 20 mM glucose only when fed with beef tallow, and not when fed with safflower oil. Linolenic acid had no effect on glucose uptake, regardless of whether it was fed with beef tallow or safflower oil. The jejunal uptake a long-chain fatty acids (18∶0, 18∶2ω6, 18∶3ω3, 20∶4ω6, 20∶5ω3 and 22∶6ω3) and cholesterol was lower in salfflower oil than with beef tallow. When eicosapentaenoic acid/docosahexaenoic acid was given with beef tallow (but not with safflower oil), there was lower uptake of 18∶0, 20∶5ω3 and cholesterol. The demonstration of the inhibitory effect of linolenic acid or eicosapentaenoic acid/docosahexaenoic acid on cholesterol uptake required the feeding of a saturated fatty acid diet (beef tallow). These changes in uptake were not explained by differences in the animals’ food intake, body weight gain or intestinal weight. Feeding safflower oil was associated with an approximately 25% increase in the jejunal and ileal mucosal surface area, but this increase was prevented by combining linolenic acid or eicosapentaenoic acid/docosahexaenoic acid with safflower oil. Different inhibitory patterns were observed when mixtures of fatty acids were present together in the incubation medium, rather than in the diet: for example, when 18∶0 was in the incubation medium with 20∶4ω6, the uptake of 20∶4ω6 was reduced, whereas the uptake was unaffected by 18∶2ω6 or 20∶5ω3. Thus, (1) the inhibitory effect of eicosapentaenoic acid/docosahexaenoic acid on jejunal uptake of glucose, fatty acids and cholesterol was influenced by the major dietary lipid, saturated (beef tallow) or polyunsaturated fatty acid (safflower oil); and (2) different omega-3 fatty acids (linolenic acid versus eicosapentaenoic acid/docosahexaenoic acid) have a variable influence on the intestinal absorption of nutrients.     

The effect of dietary fat level and quality on plasma lipoprotein lipids and plasma fatty acids in normocholesterolemic subjects

This study examined the effect on the plasma lipids and plasma phospholipid and cholesteryl ester fatty acids of changing from a typical western diet to a very low fat (VLF) vegetarian diet containing one egg/day. The effect of the addition of saturated, monounsaturated or polyunsaturated fat (PUFA) to the VLF diet was also examined. Three groups of 10 subjects (6 women, 4 men) were fed the VLF diet (10% energy as fat) for two weeks, and then in the next two weeks the dietary fat in each group was increased by 10% energy/week using butter, olive oil or safflower oil. The fat replaced dietary carbohydrate. The VLF diet reduced both the low density lipoprotein (LDL)-and high density lipoprotein (HDL)-cholesterol levels; addition of the monounsaturated fats and PUFA increased the HDL-cholesterol levels, whereas butter increased the cholesterol levels in both the LDL- and HDL-fractions. The VLF diet led to significant reductions in the proportion of linoleic acid (18∶2ω6) and eicosapentaenoic acid (20∶5ω3) and to increases in palmitoleic (16∶1), eicosatrienoic (20∶3ω6) and arachidonic acids (20∶4ω6) in both phospholipids and cholesteryl esters. Addition of butter reversed the changes seen on the VLF diet, with the exception of 16∶1, which remained elevated. Addition of olive oil resulted in a significant rise in the proportion of 18∶1 and significant decreases in all ω3 PUFA except 22∶6 compared with the usual diet. The addition of safflower oil resulted in significant increases in 18∶2 and 20∶4ω6 and significant decreases in 18∶1, 20∶5ω3 and 22∶5ω3. These results indicate that the reduction of saturated fat content of the diet (<6% dietary energy), either by reducing the total fat content of the diet or by exchanging saturated fat with unsaturated fat, reduced the total plasma cholesterol levels by approximately 12% in normocholesterolemic subjects. Although the VLF vegetarian diet reduced both LDL- and HDL-cholesterol levels, the long-term effects of VLF diets are unlikely to be deteterious since populations which habitually consume these diets have low rates of coronary heart disease. The addition of safflower oil or olive oil to a VLF diet produced favorable changes in the lipoprotein lipid profile compared with the addition of butter. The VLF diets and diets rich in butter, olive oil or safflower oil had different effects on the 20 carbon eicosanoid precursor fatty acids in the plasma. This suggests that advice on plasma lipid lowering should also take into account the effect of the diet on the fatty acid profile of the plasma lipids.     

Δ15, 18-tetracosadienoic acid content of sphingolipids from platel and erythrocytes of animals fed diets high in saturated or polyunsaturated fats

The effect of diets high (15%) in saturated (beef tallow) or polyunsaturated (corn or cottonseed oil) fatty acids on the fatty acid composition of sphingomyelin from canine erythrocytes and platelets and sphingomyelin and neutral glycosphingolipids of swine erythrocytes was determined. Sphingolipids of platelets and erythrocytes from animals fed high levels of corn or cottonseed oil exhibited a dramatic alteration in their fatty acid composition, most notable of which was a 50% reduction in nervonic acid (24∶1ω9) as compared to levels observed in control or tallow fed animals. This decrease was compensated for by a quantitatively similar increase in a C₂₄ dienoic acid. The long chain dienoic acid was isolated by silver nitrate thin layer chromatography and determined by analysis of its oxidation products to be Δ15, 18-tetracosadienoic acid (24∶2ω6). When the animals were fed the diets high in polyunsaturates, the 24∶2ω6 represented 13, 20, and 9% of the sphingomyelin fatty acids from canine erythrocytes, platelets, and swine erythrocytes, respectively, and 5% of the neutral glycosphingolipid fatty acids of swine erythrocytes. In contrast, the 24∶2ω6 represented less than 4% of the total cellular sphingolipid fatty acids in animals fed the control or high beef tallow diets. The 24∶1ω9 in the sphingolipids of the animals fed the polyunsaturated diet was roughly equal to that of 24∶2ω6, whereas in the sphingolipids of animals fed the control or saturated fat (beef tallow) diet, the 24∶1ω9 was twice these values. Since sphingomyelin is a membrane component, the increase in unsaturation (24∶2ω6) in its fatty acid moiety induced by dietary polyunsaturates may affect membrane fluidity and may alter membrane properties. Dr. Nelson’s current affiliation is with the Lipid Metabolism Branch, Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute.     

Diets rich in lean beef increase arachidonic acid and long-chain ω3 polyunsaturated fatty acid levels in plasma phospholipids

Diets rich in meat are claimed to contribute to the high tissue arachidonic acid (20∶4ω6) content in people in Westernized societies, but there are very few direct data to substantiate this assertion. Because meat contains a variety of long-chain polyunsaturated fatty acids (PUFA) that are susceptible to oxidation, we initially examined the effect of cooking on the long-chain PUFA content of beef, and then determined the effect of ingestion of lean beef on the concentration of long-chain PUFA in plasma phospholipids (PL). First, we examined the effect of grilling (5–15 min) and frying (10 min) different cuts of fat-trimmed lean beef on the long-chain PUFA content. Second, we investigated the effect of including 500 g lean beef daily (raw weight) for 4 wk on the fatty acid content and composition of plasma PL in 33 healthy volunteers. This study was part of a larger trial investigating the effect of lean beef on plasma cholesterol levels. In the first two weeks, the subjects ate a very low-fat diet (10% energy) followed by an increase in the dietary fat by 10% each week for the next 2 wk. The added fat consisted of beef fat, or olive oil (as the oil or a margarine) or safflower oil (as the oil or a margarine). This quantity of beef provided 60, 230, 125, 140 and 20 mg/d, respectively, of eicosatrienoic acid (20∶3ω6), 20∶4ω6, eicosapentaenoic acid (20∶5ω3), docosapentaenoic acid (22∶5ω3) and docosahexaenoic acid (22∶6ω3). Grilling for 10–15 min, but not frying, of the fat-trimmed lean beef resulted in 20–30% losses of the 20 and 22 carbon PUFA. The consumption of the lean beef during the first two-week period, when there was a very low level of dietary fat, was associated with significant increases in the proportion and concentration of 20∶3ω6, 20∶4ω6, 20∶5ω3 and 22∶5ω3 in the plasma PL and a significant decrease in the proportion and content of 18∶2ω6. The addition of beef fat or olive oil to the diets containing lean beef did not alter the plasma PL fatty acid profile compared with the very low-fat diet, whereas the addition of safflower oil maintained the significant increases in 20∶4ω6 and 22∶5ω3 but led to decreases in 18∶3ω3 and 20∶5ω3 compared with the very lowfat diet. The results showed that diets rich in lean beef increased the 20∶3ω6, 20∶4ω6 and the long-chain ω3 PUFA levels in the plasma PL. A high level of linoleic acid in diets rich in lean beef prevented the rise in the plasma level of 20∶3ω6 and 20∶5ω3, two fatty acids known to antagonize the effects of 20∶4ω6 on platelet aggregation.     

Response of free and esterified plasma cholesterol levels in the mongolian gerbil to the fatty acid composition of dietary lipid

The present study was undertaken to investigate the potential suitability of the Mongolian gerbil as a useful animal model to study the effects of dietary fats on plasma cholesterol levels. Semipurified diets containing either 20% lard, 20% safflower oil, or 19.5% beef tallow +0.5% safflower oil were equalized to contain 0.01% cholesterol and 0.05% plant sterol and were fed for a four week experimental period. The proportions of total calories contributed by fat, protein and carbohydrate (starch/sucrose ratio of 2∶1) were 40, 14 and 46%, respectively, so as to approach the distribution of calories within the average North American diet. Free, esterified, and total plasma cholesterol levels of male gerbils were determined weekly by gas liquid chromatography after drawing blood via a serial sampling technique. After 1, 2, 3, and 4 weeks of feeding the experimental diets, total cholesterol levels were lowest in the safflower oil fed animals; the corresponding values were 19–64% greater in gerbils fed lard and 68–91% greater in those consuming the beef tallow diet. Cholesterol in the free form generally responded more dramatically to the type of dietary lipid than did cholesterol in the ester form. Irrespective of the type of dietary lipid or the length of the feeding trial, 18–23% of the total plasma cholesterol was in the free form and 77–82% was present as the ester. In view of the similarity to the human of the relative proportions of free versus esterified cholesterol, the type of cholesteryl esters, and their response to dietary manipulation, the gerbil appears to be a useful animal model for studying the regulatory effect of dietary lipid on plasma cholesterol levels. Presented in part at the A.O.C.S. Annual Meeting, San Francisco, CA, May 1979.     

Dietary α-linolenic acid lowers postprandial lipid levels with increase of eicosapentaenoic and docosahexaenoic acid contents in rat hepatic membrane

This study was designed to examine the effects of dietary n−3 and n−6 polyunsaturated fatty acids (PUFA) on postprandial lipid levels and fatty acid composition of hepatic membranes. Male Sprague-Dawley rats were trained for a 3−h feeding protocol and fed one of five semipurified diets: one fat-free diet or one of four diets supplemented with 10% (by weight) each of corn oil, beef tallow, perilla oil, and fish oil. Two separate experiments were performed, 4-wk long-term and 4-d short-term feeding models, to compare the effects of feeding periods. Postprandial plasma lipid was affected by dietary fats. Triacylglycerol (TG) and total cholesterol levels were decreased in rats fed perilla oil and fish oil diets compared with corn oil and beef tallow diets. Hepatic TG and total cholesterol levels were also reduced by fish oil and perilla oil diets. Fatty acid composition of hepatic microsomal fraction reflected dietary fatty acids and their metabolic conversion. The major fatty acids of rats fed the beef tallow diet were palmitic, stearic, and oleic. Similarly, linoleic acid (LA) and arachidonic acid in the corn oil group, α-linolenic acid (ALA) and eicosapentaenoic acid (EPA) in the perilla oil group, and palmitic acid and docosahexaenoic acid (DHA) in the fish oil group were detected in high proportions. Both long- and short-term feeding experiments showed similar results. In addition, microsomal DHA content was negatively correlated with plasma lipid levels. Hepatic lipid levels were also negatively correlated with EPA and DHA contents. These results suggest that n−3 ALA has more of a hypolipidemic effect than n−6 LA and that the hypolipidemic effect of n−3 PUFA may be partly related to the increase of EPA and DHA in hepatic membrane.     

Incorporation of n−3 fatty acids into plasma and liver lipids of rats: Importance of background dietary fat

The health benefits of long-chain n−3 PUFA (20∶5n−3 and 22∶6n−3) depend on the extent of incorporation of these FA into plasma and tissue lipids. This study aimed to investigate the effect of the background dietary fat (saturated, monounsaturated, or n−6 polyunsaturated) on the quantitative incorporation of dietary 18∶3n−3 and its elongated and desaturated products into the plasma and the liver lipids of rats. Female weanling Wistar rats (n=54) were randomly assigned to six diet groups (n=9). The fat added to the semipurified diets was tallow (SFA), tallow plus linseed oil (SFA-LNA), sunola oil (MUFA), sunola oil plus linseed oil (MUFA-LNA), sunflower oil (PUFA), or sunflower oil plus linseed oil (PUFA-LNA). At the completion of the 4-wk feeding period, quantitative FA analysis of the liver and plasma was undertaken by GC. The inclusion of linseed oil in the rat diets increased the level of 18∶3n−3, 20∶5n−3, and, to a smaller degree, 22∶6n−3 in plasma and liver lipids regardless of the background dietary fat. The extent of incorporation of 18∶3n−3, 20∶5n−3, and 22∶5n−3 followed the order SFA-LNA>MUFA-LNA>PUFA-LNA. Levels of 22∶6n−3 were increased to a similar extent regardless of the type of major fat in the rat diets. This indicates that the background diet affects the incorporation in liver and plasma FA pools of the n−3 PUFA with the exception of 22∶6n−3 and therefore the background diet has the potential to influence the already established health benefits of long-chain n−3 fatty acids.     

Modulation of tissue prostaglandin synthesizing capacity by increased ratios of dietary alpha-linolenic acid to linoleic acid

Semipurified diets containing ratios of α-linolenic acid (18∶3ω3) to linoleic acid (18∶2ω6) of 1/32, 1/7, 1/1, and 3.5/1 in the form of corn oil, soybean oil, soybean/linseed oil mix and linseed oil were fed to rats for 2 months. The first 3 diets were fed to another group of rats for 4 months and to a group through the second generation. Fatty acid analysis of liver and spleen ethanolamine glycerophosphatide revealed that, as the level of 18∶3ω3 in the diet increased, the elongated, desaturated metabolites of the ω6 series decreased and the ω3 series increased. Noteworthy was the depression in the amount of the precursor of the 2-series prostaglandins (PG) as the ω3 levels increased. Synthesis of PG by liver of rats fed 2 or 4 months markedly decreased, but at 2 months in thymus and spleen, it showed a trend toward decreasing only. Brain slices showed no decrease in PGF_2α synthesis after 4 months, but did decrease significantly after feeding the diets to the second generation. Synthesis of PGE₂ by spleen homogenate from the second generation also significantly decreased. The replacement of ω6 series fatty acids by ω3 series is explained by the effective competition of 18∶3ω3 over 18∶2ω6 for the Δ6 desaturase. Depressions in PG synthesis by high dietary 18∶3ω3 is explained by the competitive inhibition of the PG synthetase complex by 20∶5ω3 as well as by the decreased levels of 20∶4ω6. Part of a dissertation submitted by Lisa A. Marshall in partial fulfillment of requirements for the Ph.D. degree in Nutritional Sciences. Presented in part at the 72nd AOCS annual meeting, New Orleans, May 1981.     

Chronic administration of eicosapentaenoic acid and docosahexaenoic acid as ethyl esters reduced plasma cholesterol and changed the fatty acid composition in rat blood and organs

Fish oils rich in n-3 fatty acids have been shown to decrease plasma lipid levels, but the underlying mechanism has not yet been elucidated. This investigation was performed in order to further clarify the effects of purified ethyl esters of eicosapentaenoic acid (EPA-EE) and docosahexaenoic acid (DHA-EE) on lipid metabolism in rats. The animals were fed EPA-EE, DHA-EE, palmitic acid, or corn oil (1 g/kg/d) by orogastric intubation along with a chow background diet for three months. At the end the animals were sacrificed. Plasma and liver lipids were measured, as well as lipid-related enzyme activities and mRNA levels. The fatty acid composition of plasma and different tissues was also determined. This study shows that, compared to the corn oil control, EPA-EE and DHA-EE lowered plasma cholesterol level, whereas only EPA-EE lowered the amount of plasma triacylglycerol. In liver peroxisomes, both EE preparations increased fatty acyl-CoA oxidase FAO activities, and neither altered 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activities. In liver microsomes, EPA-EE raised HMG-CoA reductase and acyl-CoAicholesterol acyltransferase activities, whereas DHA-EE lowered the former and did not affect the latter. Neither product altered mRNA levels for HMG-CoA reductase, low density lipoprotein-receptor, or low density lipoprotein-receptor related protein. EPA-EE lowered plasma triacylglycerol, reflecting lowered very low density lipoprotein secretion, thus the cholesterol lowering effect in EPA-EE-treated rats may be secondary to the hypotriacylglycerolemic effect. An inhibition of HMG-CoA reductase activity in DHA-EE treated rats may contribute to the hypocholesterolemic effect. The present study reports that 20∶5n-3, and not 22∶6n-3, is the fatty acid primarily responsible for the triacylglycerol lowering effect of fish oil. Finally, 20∶5n-3 was not converted to 22∶6n-3, whereas retroconversion of 22∶6n-3 to 20∶5n-3 was observed.     

Effect of dietary linolenic acid and docosahexaenoic acid on growth and fatty acid composition of rainbow trout (Salmo gairdneri)

Methyl linolenate 18∶3ω3 and docosahexaenoate 22∶6ω3 were incorporated in semipurified diets at several levels and fed to trout previously maintained on a fat-free diet. After 14 weeks, the weight gain and feed conversion of the fish on each diet were determined. The fatty acid composition of the lipid from each group of fish was analyzed by gas liquid chromatography. Both 18∶3ω3 and 22∶6ω3 fed at the 1% level supported maximum growth of the fish. The control group, which were fed no ω3 fatty acids, exhibited a shock syndrome, poor appetite and a very slow growth rate. Tissue fatty acid analysis revealed eicosatrienoic acid 20∶3ω9 accumulated in the phospholipid fraction of this group. The 20∶3ω9 level was lowered when either 18∶3ω3 or 22∶6ω3 was included in the diet. Analysis showed that the dietary 18∶3ω3 was rapidly converted by the fish into 22∶6ω3 with a high concentration in the phospholipid. However 22∶6ω3 fed to the fish remained unchanged and little or no retroconversion of this fatty acid was observed. Presented in part at the AOCS Meeting, Atlantic City, October 1971. Technical paper no. 3247, Oregon Agricultural Experiment Station.     

Lipid metabolism and FA composition in tissues of Eurasian perch Perca fluviatilis as influenced by dietary fats

Eurasian perch, Perca fluviatilis, were fed a semipurified fat-free diet for 4 wk, followed by a 16% feeding supplementation of either olive oil (OO), safflower oil (SO), linseed oil (LO), or cod liver oil (CLO) as the only lipid source in each diet for 10 wk. Significant reductions in total lipid of tissues were observed (31.4% in viscera, 66.7% in muscle, and 74.1% in liver) after feeding the fat-free diet. The SO-, LO-, and CLO-fed fish significantly increased lipid deposition in liver and viscera compared to fish fed the OO diet; however, muscle lipid levels were not significantly affected. Large amounts of dietary 18∶1n−9 were incorporated directly into tissue lipids when fish were fed the OO diet. The LO diet significantly elevated 18∶4n−3, 20∶5n−3, 22∶5n−3, and 22∶6n−3 in the liver compared to fish fed OO or SO diets, and the n−3/n−6 ratio was 16 times that of the SO group, with significantly high desaturation and elongation products of 18∶3n−3. These results suggest that Δ6 and Δ5 desaturases are highly active in Eurasian perch, and that the enzymes at this dietary n−3/n−6 ratio favor 18∶3n−3 over 18∶2n−6 as substrate. The SO diet significantly increased 18∶3n−6, 20∶3n−6, and 22∶5n−6 in the liver and significantly decreased EPA and DHA. This indicates that desaturation enzymes were not specifically favoring n−3 over n−6 acids in perch lipid metabolism, and that these elongation and desaturation enzymes were influenced by n−3 and n−6 FA content in the diet. The present study indicates that high tissue content of DHA in the muscle of Eurasian perch was attributable to the greater ability for n−3 acid bioconversion.     

Dietary oxidized cholesterol modulates cholesterol metabolism and linoleic acid desaturation in rats fed high-cholesterol diets

The interactive effect of high dietary levels of oxidized cholesterol on exogenous cholerterol and linoleic acid metabolism was examined in male 4-wk-old Sprague-Dawley rats given high-cholesterol diets. The rats were pair-fed purified diets free of or containing either 0.5% cholesterol alone or both 0.5% cholesterol and 0.5% oxidized cholesterol mixture (containing 93% oxidized cholesterol) for 3 wk. Hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity was reduced in rats given cholesterol alone or both cholesterol and oxidized cholesterol. However, hepatic cholesterol 7α-hydroxylase activity was lowered only when rats were given both cholesterol and oxidized cholesterol, although dietary cholesterol increased this activity. Reflecting this effect, acidic steroid excretion was lowest among the groups of rats given cholesterol and oxidized cholesterol. On the other hand, the activity of hepatic Δ6 desaturase, a key enzyme in the metabolism of linoleic acid to arachidonic acid, was increased in rats given both cholesterol and oxidized cholesterol, although dietary cholesterol alone lowered its activity. As a result, the Δ6 desaturation index, 20∶3n-6+20∶4n-6/18∶2n-6, in liver and serum phosphlipids tended to be higher in the group fed both cholesterol and oxidized cholesterol than in the one fed cholesterol alone. Thus, dietary oxidized cholesterol significantly modulated exogenous cholesterol metabolism and promoted linoleic acid desaturation even when it was given at high levels together with a high cholesterol diet.     

Dietary α-linolenic acid increases brain but not heart and liver docosahexaenoic acid levels

Fish oil-enriched diets increase n−3 FA in tissue phospholipids; however, a similar effect by plant-derived n−3 FA is poorly defined. To address this question, we determined mass changes in phospholipid FA, individual phospholipid classes, and cholesterol in the liver, heart, and brain of rats fed diets enriched in flax oil (rich in 18∶3n−3), fish oil (rich in 22∶6n−3 and 20∶5n−3), or safflower oil (rich in 18∶2n−6) for 8 wk. In the heart and liver phospholipids, 22∶6n−3 levels increased only in the fish oil group, although rats fed flax oil accumulated 20∶5n−3 and 22∶5n−3. However, in the brain, the flax and fish oil diets increased the phospholipid 22∶6n−3 mass. In all tissues, these diets decreased the 20∶4n−6 mass, although the effect was more marked in the fish oil than in the flax oil group. Although these data do not provide direct evidence for 18∶3n−3 elongation and desaturation by the brain, they demonstrate that 18∶3n−3-enriched diets reduced tissue 20∶4n−6 levels and increased cellular n−3 levels in a tissuedependent manner. We hypothesize, based on the lack of increased 22∶6n−3 but increased 18∶3n−3 in the liver and heart, that the flax oil diet increased circulating 18∶3n−3, thereby presenting tissue with this EFA for further elongation and desaturation.     

Modulation of prostaglandin synthesis in rat peritoneal macrophages with ω-3 fatty acids

In view of the findings that ω3 fatty acids inhibit the synthesis of prostaglandins (PG) from arachidonic acid (20∶4ω6) and that among immunologically active cells, the macrophage, is a major producer of PG, we undertook a study of the effect of dietary α-linolenic acid (18∶3ω3) on PG synthesis in the macrophage. Rats were fed purified diets containing either 10% corn oil (CO) or linseed oil (LO), providing either a low (1/32) or high (3.5/1) ratio of 18∶3ω3 to 18∶2ω6, respectively, for 6 weeks. Fatty acid analysis of macrophage phospholipids showed that there was an appreciable increase in the percentage of ω3 fatty acids and a decrease in the ω6 fatty acids in macrophages from rats fed the LO diet. The changes in fatty acid composition were associated with a significant decrease in the synthesis of prostaglandin E (PGE) by macrophages from rats fed the LO diet. Macrophages from rats fed the 2 dietary, oils did not differ in their ability to degrade PG, thus the difference in PG production appeared to be a consequence of decreased synthesis only. The dietarily induced changes in PGE synthesis were readily overcome in vitro by culturing macrophages with complexes of fat-free bovine serum albumin and either 20∶4ω6 or 20∶5ω3. Part of a dissertation submitted by Linda J. Magrum in partial fulfillment of the requirements for the Ph.D. degree in Nutritional Sciences. Honored Student Presentation at the AOCS 74th Annual Meeting, Chicago, 1983.     

Effect of dietary fat on the lipid composition and utilization of short-chain fatty acids by rat colonocytes

The objective of the present studies was to examine the effect of dietary fat on the lipid composition of rat colonocytes and their utilization of short-chain fatty acids (SCFA). Rats were fed 14% beef fat, fish oil or safflower oil plus 2% corn oil in a semi-synthetic base diet for 4 wk. Colonocytes were isolated and their lipid composition was examined. Feeding beef fat and fish oil resulted in an increase in monounsaturated fatty acids and a reduction in ω-6 fatty acids. Feeding fish oil resulted in an enrichment with ω-3 fatty acids. These was no dietary influence on the amount of either cholesterol or phospholipids of colonocytes. Fish oil feeding resulted in significant increase in colonocyte free fatty acids (FFA) as compared to other diets. Dietary fat was found to have no effect on SCFA utilization by colonocytes. Colonocytes were found to utilize SCFA in the order of butyrate ≥acetate ≥propionate. The presence of acetate and propionate in the medium had no effect on the rate of butyrate utilization.     

A diet containing n−3 and n−6 fatty acids favorably alters the renal phospholipids,eicosanoid synthesis and plasma lipids in nephrotic rats

The nephrotic syndrome was induced in rats by intravenous adriamycin (3 mg/kg). The rats were then divided into four groups which, for six weeks, were pair-fed diets containing beef tallow (BT), fish oil (FO), a source of n−3 fatty acids, evening primrose oil (EPO), a source of n−6 fatty acids, or a combination of evening primrose oil and fish oil, 75∶25 (EPO:FO). The fat content of the diets was 15%. Significant incorporation of the fatty acids into kidney phospholipids was demonstrated. Diets containing FO, EPO and EPO:FO lowered plasma triglycerides and total cholesterol levels as compared with diets containing BT. Only EPO:FO raised high density lipoprotein (HDL) cholesterol levels, as compared with BT. The combination EPO:FO prevented the tenfold suppression of aortic 6-keto-PGF_1α caused by FO. These changes in plasma lipids and eicosanoid production are potentially antiatherogenic and may prevent glomerular sclerosis. The combination of EPO and FO, containing n−6 and n−3 fatty acids may offer advantages over either family of fatty acids in this model of nephrotic syndrome.