Effect of dietary fat upon aflatoxicosis in rats fed torula yeast containing diet

This study was designed to study the possible interrelationships between Torula yeast, vitamin E, and the dietary fat source on aflatoxin-induced tumors. Rats were fed Torula yeast-containing basal diets which included 1.7 ppm aflatoxin B₁ with either lard, corn oil or no fat, and with or without vitamin E supplements for 3 months. Thereafter, the respective diets without aflatoxin were fed for ca. 9 months. Animals receiving the vitamin E-deficient diets had a high mortality. Although the vitamin E-deficient, aflatoxin-treated rats had lower wt gains than did the vitamin E-deficient controls, they lived twice as long. In addition, regardless of the dietary fat source, the kidneys and adrenals of these vitamin E-deficient, aflatoxin-supplemented rats were found to be significantly heavier than the controls, and plasma cholesterol levels were elevated. Increased amounts of liver lipid were observed in response to aflatoxin in both corn oil-fed and fat-deficient rats. No such differences were observed in the responses of the vitamin E-supplemented groups to aflatoxin. On the corn oil diet, aflatoxin administration resulted in an increased deposition of polyunsaturated fatty acids in cholesteryl ester and phospholipid fractions in livers of vitamin E-deficient rats and the phospholipid fraction of vitamin E-sufficient rats. The vitamin E-deficient rats exhibited necrosis of the liver, which was alleviated when aflatoxin was included in the diet, and calcification of the kidneys, which was potentiated by the dietary aflatoxin. No tumors were observed in these animals. In animals maintained on vitamin E-sufficient diets for 1 year, growth was depressed as a result of aflatoxin administration with the greatest depression occurring in the group fed corn oil. Spleen wt were decreased in all groups given aflatoxin. However, there were no changes in either plasma or liver cholesterol or total liver lipids which could be attributed to aflatoxin administration. When aflatoxin was fed with lard, the cholesteryl ester, triglyceride, and free fatty acid fractions of plasma had decreased amounts of the C20:4 acid. In the cholesteryl ester fraction only, this change was accompanied by increased levels of C16:0, C18:0, and C18:1 acids. In the liver phospholipids, there were increased levels of mono- and polyunsaturated fatty acids and decreases in the saturated fatty acids. All of the animals receiving aflatoxin exhibited severe necrosis and tumor formation in the kidneys; the animals fed lard had the highest level of involvement and those in the fat-free group the least. Liver pathology was the least marked among the rats fed the fat-free diet. Since aflatoxin-induced tumors are rich in lipids, the fat-free diet may be protective to the animal.     

Increased plasma triglyceride secretion in EFA-deficient rats fed diets with or without saturated fat

Metabolic responses to essential fatty acid-deficiency in rats include an increased rate of triglyceride secretion into the plasma, a large reduction in the HDL₁ plasma lipoprotein concentration, and increased concentrations of liver triacylglycerols and cholesteryl esters. Because of differences in the types of EFA-deficient diets used, it is not clear whether these responses were solely due to the absence of EFA from the diet or whether saturated fat, or differences in acyl group chain length in this fat, might be responsible. Therefore, we fed rats diets differing only in amounts and kinds of fat, and measured triacylglycerol secretion rates and liver concentrations of triacylglycerols and cholesteryl esters, for comparison with our earlier measurements of plasma high density lipoprotein subpopulations in rats fed exactly the same diets. The purified diets contained either no fat, 5% by weight hydrogenated coconut oil, 5% hydrogenated cottonseed oil, or each of these three diets supplemented with 1% safflower oil, or 5% corn oil. We also fed some rats a nonpurified stock diet for comparison with literature reports. The present results indicate that the metabolic responses to essential fatty acid deficiency described above are definitely due to essential fatty acid-deficiency and not to the presence or chain length of acyl groups in saturated fat in the diet. Presented in part at the May 1984 meeting of the American Oil Chemists' Society in Dallas, Texas.     

Dihomo-γ-linolenic acid reverses hypertension induced in rats by diets rich in saturated fat

This study has shown that hypertension induced in rats by a diet rich in saturated fat (16% coconut oil, 4% palmitic acid by weight) is reversed by the addition of the essential fatty acid, dihomo-γ-linolenic acid (DHLA), at 5.0% but not at 0.5% of dietary energy. This potent effect of DHLA has been attributed to modulation of prostaglandin biosynthesis.     

Dietary factors and aflatoxin toxicity: II. effect of fat source upon aflatoxicosis in rats

Previous studies in this laboratory have indicated that the tumorigenic and biochemical response of rats to aflatoxin may be affected by diet. To clarify the possible importance of the fat component of the diet in altering these biochemical responses a cross-over experiment was devised in which peanut oil and lard were reversed in two diets containing different protein sources and vitamin mixtures. It was found that more concentrated doses of aflatoxin administered for a shorter period of time had a more inhibitory effect upon growth, and liver pathology also appeared to be worse than when smaller doses were given for longer periods of time. There were slight differences in pathology due to the basal diet among peanut oilfed rats, and large differences when the fat component was lard. Plasma cholesterol levels were elevated as a result of the aflatoxin administration, regardless of the diet, and liver cholesterol levels were elevated in response to aflatoxin when diets containing the more varied protein source were fed. In all fractions of plasma fatty acids, fatty acid patterns similar to those observed in marginal essential fatty acid deficiency were seen when lard was fed. The observations that the more restricted protein diet or some component of it, reacts with lard to produce signs similar to those typical of essential fatty acid deficiency and that this regimen produces the most severe liver pathology further establishes the importance of the diet as a means of modifying the response of the organism to aflatoxin.     

Acetoacetate metabolism of rats fed high fat or restricted calorie diets

Ethyl-¹⁴C-acetoacetate was used to trace oxidation and metabolism of acetoacetate when rats were fed a high fat diet (80% of total calories from beef tallow or corn oil, carbohydrate free), a high carbohydrate diet (2% corn oil) or a high carbohydrate diet with restriction of calories to one half of ad lib. consumption for two weeks. The rate of expiration of¹⁴CO₂ in all groups of animals did not differ significantly and was not related to plasma concentration of acetoacetate. The high fat diets slightly enhanced the oxidation of acetoacetate to¹⁴CO₂ over a 3 hr period compared to other diets. Incorporation of acetoacetate into fatty acids did not differ significantly among groups. Rats fed the high carbohydrate diet ad lib. incorporated into liver cholesterol more acetoacetate than did any other group, but dietary unsaturated fat resulted in greater incorporation of acetoacetate into cholesterol than saturated fat. High calorie and high beef tallow groups were ketonemic but the low concentration of plasma acetoacetate in rats fed a high corn oil diet indicates that unsaturated fatty acids are not ketogenic. The data show that utilization of acetoacetate is not significantly reduced in a ketonemic condition and support the premise that overproduction of ketone bodies is the cause of ketonemia. Rats appeared to be normal during the two-week period when no carbohydrate was included in the diet. Presented at the AOCS Meeting, Chicago, October, 1967.     

CLA isomers in milk fat from cows fed diets with high levels of unsaturated fatty acids

The concentrations of CLA isomers were determined by Ag⁺-HPLC in the milk fat of cows fed a control diet consisting of hay ad libitum and 15 kg of fodder beets or this diet supplemented with oilseeds containing either high levels of oleic acid (rapeseed), linoleic acid (sunflower seed), or α-linolenic acid (linseed). Highly significant (P≤0.001) correlations were found between the daily intakes of oleic acid and the concentration of the CLA isomer trans-7,cis-9 in milk fat; of linoleic acid and the CLA isomers trans-10,trans-12, trans-9,trans-11, trans-8,trans-10, trans-7,trans-9, trans-10,cis-12, cis-9,trans-11, trans-8,cis-10, and trans-7,cis-9; and of α-linolenic acid and the CLA isomers trans-12,trans-14, trans-11,trans-13, cis,trans/trans,cis-12,14, trans-11,cis-13, and cis-11,trans-13. CLA concentrations were also determined in the milk fat of cows grazing in the lowlands (600–650 m), the mountains (900–1210 m), and the highlands (1275–2120 m). The concentrations of many isomers were highest in milk fat from the highlands, but only three CLA isomers (cis-9,trans-11, trans-11,cis-13, and trans-8,cis-10) showed a nearly linear increase with elevation. Therefore, these three CLA isomers, and particularly the CLA isomer trans-11,cis-13, the second-most important CLA in milk fat from cows grazing at the three altitudes, could be useful indicators of milk products of Alpine origin.     

Lung surfactant and fatty acid composition of lung tissue and lavage of rats fed diets containing different lipids

Two nutritional models, essential fatty acid (EFA) deficiency and the feeding of saturated vs unsaturated fats, were used to determine the effects of dietary lipids on the fatty acid composition of rat lung and lavage. Semipurified diets containing 7% corn oil, 7% hydrogenated coconut oil (EFA-deficient), 10% butter or 10% safflower oil were fed to dams during lactation and thereafter to their offspring for a total of 24 weeks. Lipids were extracted from the lung lavage and lung tissue and their fatty acid composition was determined. The content of dipalmitoylphosphatidylcholine (DPPC), the main surfactant in the lungs, was also determined. The results show that the levels of DPPC in the lungs of rats fed 10% butter decreased although the decrease in the EFA-deficient rats was greater. Comparing rats fed butter with those fed corn oil, there were also modifications in the fatty acid composition of the total lipids and phospholipids of lung tissue and lavage as well as in phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol +phosphatidylserine fractions isolated from the lung tissue. The changes in fatty acid composition were somewhat fewer in rats fed butter then in those fed an EFA-deficient diet. The results suggest that a marginal EFA deficiency produced in rats by long-term feeding of 10% butter may account for the reduction in DPPC levels and in the changes in fatty acid composition in the lung tissue and lavage.     

Hematological and lipid changes in newborn piglets fed milk-replacer diets containing erucic acid

Canola oil is not presently permitted in infant formulations in the United States because of lack of information concenring the effects of feeding canola oil to the newborn. We have previously reported a transient decrease in platelet counts and an increase in platelet size in newborn piglets fed canola oil for 4 wk, and have confirmed this in the present study. In canola oil-fed piglets, changes in platelet size and number were overcome by adding either long-chain saturated fatty acids from cocoa butter (16:0 and 18:0), or shorter-chain saturates from coconut oil (12:0 and 14:0). Feeding a high erucic acid rapeseed (HEAR) oil, with 20% 22:1n−9, led to an even greater platelet reduction and increased platelet size throughout the 4-wk trial. Bleeding times were longer in piglets fed canola oil or HEAR oil compared to sow-reared and soybean oil-fed piglets. There were no other diet-related changes. Diet-induced platelet changes were not related to platelet lipid class composition, but there were fatty acid changes. The incorporation of 22:1n−9 into platelet phospholipids of piglets fed canola oil was low (0.2–1.2%), and even for the HEAR oil group ranged from only 0.2% in phosphatidylinositol to 2.4% in phosphatidylserine. A much greater change was observed in the concentration of 24:1n−9 and in the 24:1n−9/24:0 ratio in platelet sphingomyelin (SM). The 24:1n−9 increased to 49% in the HEAR oil group compared to about 12% in animals fed the control diets (sow-reared piglets and soybean oil-fed group), while the 24:1n−9/24:0 ratio increased from about 1 to 12. Even feeding canola oil, prepared to contain 2% 22:1n−9, led to a marked increase in 24:1n−9 to 29% and had a 24:1n−9/24:0 ratio of 5. The canola oil/cocoa butter group, which also contained 2% 22:1n−9, showed a lower level of 24:1n−9 (20%) and the 24:1n−9/24:0 ratio (3) compared to the canola oil group. The results suggest that the diet-related platelet changes in newborn piglets may be related to an increase in 24:1n−9 in platelet SM, resulting from chain elongation of 22:1n−9. The inclusion of canola oil as the sole source of fat in the milk-replacer diets of newborn piglets resulted in significant platelet and lipid changes.     

Response of plasma lipids to dietary cholesterol and wine polyphenols in rats fed polyunsaturated fat diets

This experiment was designed to evaluate the effects of dietary red wine phenolic compounds (WP) and cholesterol on lipid oxidation and transport in rats. For 5 wk, weanling rats were fed polyunsaturated fat diets (n−6/n−3=6.4) supplemented or not supplemented with either 3 g/kg diet of cholesterol, 5 g/kg diet of WP, or both. The concentrations of triacylglycerols (TAG, P<0.01) and cholesterol (P<0.0002) were reduced in fasting plasma of rats fed cholesterol despite the cholesterol enrichment of very low density lipoprotein + low density lipoprotein (VLDL+LDL). The response was due to the much lower plasma concentration of high density lipoprotein (HDL) (−35%, P<0.0001). In contrast, TAG and cholesteryl ester (CE) accumulated in liver (+120 and +450%, respectively, P<0.0001). However, the cholesterol content of liver microsomes was not affected. Dietary cholesterol altered the distribution of fatty acids mainly by reducing the ratio of arachidonic acid to linoleic acid (P<0.0001) in plasma VLDL+LDL (−35%) and HDL (−42%) and in liver TAG (−42%), CE (−78%), and phospholipids (−28%). Dietary WP had little or no effect on these variables. On the other hand, dietary cholesterol lowered the α-tocopherol concentration in VLDL+LDL (−40%, P<0.003) and in microsomes (−60%, P<0.0001). In contrast, dietary WP increased the concentration in microsomes (+21%, P<0.0001), but had no effect on the concentration in VLDL+LDL. Cholesterol feeding decreased (P<0.006) whereas WP feeding increased (P<0.0001) the resistance of VLDL+LDL to copper-induced oxidation. The production of conjugated dienes after 25 h of oxidation ranged between 650 (WP without cholesterol) and 2,560 (cholesterol without WP) μmol/g VLDL+LDL protein. These findings show that dietary WP were absorbed at sufficient levels to contribute to the protection of polyunsaturated fatty acids in plasma and membranes. They could also reduce the consumption of α-tocopherol and endogenous antioxidants. The responses suggest that, in humans, these substances may be beneficial by reducing the deleterious effects of a dietary overload of cholesterol.     

Short-Term changes in hepatic HMG-CoA reductase in rats fed diets containing cholesterol or oat bran

In vivo regulation of hepatic HMG-CoA reductase (HMGR) (mevalonate: NADP⁺ oxidoreductase [acylating CoA]; EC 1.1.1.34] by phosphorylation/dephosphorylation has not been demonstrated. Rats were meal-fed semipurified diets; effects of inclusion of cholesterol (2%) or oat bran (15%) in a single meal on expressed (phosphorylated) and total (dephosphorylated) activities of HMGR were measured from 15 min to 4 hr after presentation of the meal. Expressed activity was not significantly altered in response to the control diet during the time periods examined, while total HMGR activity declined by 15 min and increased through 4 hr to an activity about 1.5 times control levels. Addition of cholesterol resulted in little change in expressed activity but a greater and more sustained reduction in total activity. Oat bran caused reductions in both total and expressed activities, which were maintained through 4 hr. Total HMGR activity was best correlated with apparent demand for cholesterol synthesis.     

Effects of dietary saturated fat on erucic acid induced myocardial lipidosis in rats

Male Sprague-Dawley rats were fed for one week diets containing 20% by weight fat/oil mixtures with different levels of erucic acid (22∶1n−9) (∼2.5 or 9%) and total saturated fatty acids (∼8 or 35%). Corn oil and high erucic acid rapeseed (HEAR) oil were fed as controls. The same hearts were evaluated histologically using oil red O staining and chemically for cardiac triacylglycerol (TAG) and 22∶1n−9 content in cardiac TAG to compare the three methods for assessing lipid accumulation in rat hearts. Rats fed corn oil showed trace myocardial lipidosis by staining, and a cardiac TAG content of 3.6 mg/g wet weight in the absence of dietary 22∶1n−9. An increase in dietary 22∶1n−9 resulted in significantly increased myocardial lipidosis as assessed histologically and by an accumulation of 22∶1n−9 in heart lipids; there was no increase in cardiac TAG except when HEAR oil was fed. An increase in saturated fatty acids showed no changes in myocardial lipid content assessed histologically, the content of cardiac TAG or the 22∶1n−9 content of TAG at either 2.5 or 9% dietary 22∶1n−9. The histological staining method was more significantly correlated to 22∶1n−9 in cardiac TAG (r=0.49;P<0.001) than to total cardiac TAG (r=0.40;P<0.05). The 22∶1n−9 content was highest in cardiac TAG and free fatty acids. Among the cardiac phospholipids, the highest incorporation was observed into phosphatidylserine, followed by sphingomyelin. With the addition of saturated fat, the fatty acid composition showed decreased accumulation of 22∶1n−9 and increased levels of arachidonic and docosahexaenoic acids in most cardiac phospholipids, despite decreased dietary concentrations of their precursor fatty acids, linoleic and linolenic acids.     

Effects of polyphenolic natural products on the lipid profiles of rats fed high fat diets

Male Wistar rats were fed a high fat diet (HFD) containing 2.5% cholesterol and 16% lard supplemented with polyphenolic natural products namely quercetin, morin or tannic acid (100 mg/rat/day) for 4, 7 and 10 wk. Rats fed HFD without the supplements served as control. The effects of these compounds on blood lipid profiles, enzymes, liver fat and aorta of the rat were studied. In rats fed HFD containing tannic acid, plasma total cholesterol (TC), low density lipoprotein cholesterol (LDLC) and triglyceride (TG) were reduced by 33.3%, 29.6% and 65.1%, respectively, at week 10. High density lipoprotein cholesterol (HDLC) concentration was not altered. Fat deposition was also decreased in the liver of these rats. Morin significantly reduced plasma TG (65.1%) and liver fat only at week 7 while at week 10 it reduced plasma TC and LDLC by 30.9% and 29.3% respectively. The plasma HDLC concentration was increased by 47.3% at week 4 but no effect was seen at weeks 7 and 10. In the rats fed HFD containing quercetin, plasma HDLC was increased by 28.6% at week 7 but at week 10, plasma LDLC was increased by 21.2%. Quercetin did not cause any significant changes on the plasma TC, TG and liver fat at weeks 4, 7 and 10. Plasma alanine aminotransferase, alkaline phosphatase and bilirubin in control and treated groups were not significantly different. However, hepatic lipase activity in rats fed tannic acid was significantly lower. Aortae of all groups of rats showed no abnormalities. The present report indicates that tannic acid and morin are effective in reducing plasma and liver lipids when supplemented with a high fat diet in rats.     

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.     

Liver subcellular fatty acid profiles of chicks fed diets containing hydrogenated fats and varying linoleate levels

Day-old male broiler chickens were fed semipurified diets containing 5% lipid from one of four different lipid sources: corn oil (CO), partially hydrogenated soybean oil (HSBO), a spent restaurant grease (SRG) and a purified mixture of triolein, tripalmitin and tristearin (OPS). Diets CO and HSBO contained adequate amounts of linoleic acid, but diets SRG and OPS were deficient in linoleate. In addition, SRG and HSBO containedtrans isomers of 16∶1 and 18∶1. The diets were fed for 3 wk to determine the effects of low linoleate levels andtrans isomers on fatty acid profiles in liver microsomes, mitochondria and cytosol. Chicks fed HSBO had the highest body weights, while those fed SRG and OPS had the lowest. The incidence and severity of dermatitis were similar for all treatments. The proportions of linoleate and arachidonate in lipids from liver subcecullar fractions were reduced significantly in chicks fed OPS and SRG; however levels of 20∶3ω9 were not increased. Feeding HSBO, which is high in both linoleate and linolenate, resulted in higher levels of 18∶3ω3 and 20∶5ω3 in liver subcellular fractions and lower levels of 20∶4ω6 than those seen in chicks fed CO. The isomeric forms of 18∶1 present in the partially hydrogenated fats (HSBO and SRG) appeared to be incorporated into the lipids of liver fractions. The results of this study show that dietary lipids influence fatty acid, profiles of chick liver microsomes, mitochondria and cytosol. Decreases in linoleate and arachidonate in these organelles occur before overt essential fatty acid (EFA) deficiency signs in chicks fed EFA-deficient diets. Published as Scientific Paper No. 7512, College of Agriculture and Home Economics Research Center, Project No. 4723, Washington State University, Pullman, WA.     

Hypercholesterolemia in rats fed cholesterol in agar gel diets

Female (Exp. I) or male (Exp. II) weanling rats were fed diets containing either 2% Solka-Floc or 2% agar for 28-day periods. Some groups received 1% cholesterol, either added in crystalline form or first dispersed in the oil portion of the diet, and some agar groups received their diet in a gelled form. Feces were collected for a 3-day period after 2 weeks (Exp. II) or during the fourth week (Exp. I) of experimentation. Serum and liver cholesterol, total liver lipids, fecal lipids, and fecal sterols were determined. The results indicated that cholesterol feeding increased serum cholesterol, total liver, and fecal lipids, liver cholesterol, and fecal sterols. Substitution of agar for Solka-Floc in dry (nongelled) diets further increased total liver lipids (Exp. I), but had no significant effect upon any other measured parameter. Gelling of 1% cholesterol agar diets, in contrast to the 1% cholesterol dry agar diet, resulted in reduced liver cholesterol in both experiments. Gelling significantly increased fecal sterols after 2 weeks feeding (Exp. II), but no significant differences were observed after 4 weeks feeding (Exp. I) when compared to 1% cholesterol-fed groups. Small, nonsignificant increases of liver cholesterol and total liver lipids with similar reduction of fecal sterols resulted from dispersing the cholesterol in the oil portion of the diet prior to mixing. The results indicate that (a) inclusion of 2% agar in rat diets and (b) dispersing cholesterol in oil had little effect upon serum, liver, or fecal lipids in cholesterol-fed rats. However, gelling the agar diets reduced liver cholesterol, possibly by initial reduction of dietary cholesterol absorption.     

Mammary tumorigenesis in rats fed diets high in lard

Studies were performed to examine the effect of a lard diet on tumorigenesis by 7,12-dimethylbenzanthracene (DMBA), given parenterally rather than by gavage, to eliminate any effect of the high lard diet on carcinogen absorption. In addition, the effect of low dietary levels of the antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) in the tumor model was evaluated. The lards fed were analyzed for fatty acid composition and content of certain potential contaminants. DMBA induced tumors when given by intravenous or subcutaneous injection. The high lard diet appeared to enhance tumorigenesis in rats given a dose of 0.25 mg (10% of the gavage dose) by injection into the mammary gland, although the effect was not statistically significant. In other experiments using lard from different sources and DMBA given by gavage, significant enhancement of tumorigenesis was limited to groups fed the high lard diets throughout the experiment or beginning after DMBA exposure. In contrast to earlier results, there was no demonstrable effect of feeding the high lard diets before DMBA administration. Addition of BHA and BHT to the lard at the concentration assayed in commercial lard samples or at the maximum concentration permitted did not influence the tumorigenesis. In groups in which tumorigenesis was enhanced by the high lard diet, the incidence of malignant, invasive tumors was higher than in other groups.     

Liver lipid alterations in rats fed arginine deficient diets

Arginine deficiency is associated with a marked increase in liver lipids in the rat. Triglyceride accumulation accounts for most of the fatty infiltration. Cholesterol concentration per gram of liver increased approximately 280% above control rats receiving dietary arginine. The percentage of phospholipids was significantly decreased in the arginine-deficient rat liver compared to controls. The fatty acid composition revealed a significant reduction in the percentage of palmitic, palmitoleic, oleic, and linoleic acids. However, both stearic and arachidonic acids were increased approximately 250 and 160%, respectively, in arginine-deficient livers compared to controls. Arginine deficiency in the rat causes a marked alteration in lipid metabolism similar to that observed with orotic acid feeding. The similarities of arginine deficiency and orotic acid feeding are discussed.     

Platelet and aorta arachidonic and eicosapentaenoic acid levels andin vitro eicosanoid production in rats fed high-fat diets

There is a significant interest in the interrelationship between long-chain n-3, and n-6 fatty acids due to their ability to modulate eicosanoid production. In general, the intake of arachidonic acid (AA) results in enhanced eicosanoid production, whereas n-3 polyunsaturated fatty acids (PUFA) decrease the production of eicosanoids from AA. The purpose of this study was to investigate whether the effects of dietary AA on eicosanoid production in the rat were correlated with the AA and EPA levels in platelets and aorta (eicosanoid-producing tissues). Four groups of male Sprague-Dawley rats were fed a highfat diet enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (approximately 100 mg/day of EPA+DHA) for 24 d. During the last 10 d, the four groups were orally supplemented with 0,30,60, and 90 mg/day of ethyl arachidonate. A further group of rats was fed a control diet (without longchain n-3 PUFA) for 24 d.In vitro aorta prostacyclin (PGI₂) production, serum thromboxane A₂ (TxA₂) production and plasma, and platelet and aorta phospholipid (PL) fatty acids were measured. Enriching the diet with n-3 PUFA resulted in significant reductions in tissue AA levels and an increase in the n-3 PUFA, particularly EPA. On this diet, the AA to EPA ratio was 1:1 in platelet PL, and it was 2:1 in the aorta PL. There were significant decreases in thein vitro PGI₂ and TxA₂ production compared with the control animals. The inclusion of AA in the diet resulted in marked increases in AA levels in the platelet and aorta PL with corresponding decreases in EPA. The lowest dose of AA (30 mg/rat) reversed the effects of 100 mg/day of n-3 PUFA on AA levels in platelet and aortic PL and onin vitro aorta PGI₂ and serum TxA₂ production. The dietary AA caused a differential (twofold) increase in TxA₂ relative to PGI₂ for all three levels of AA supplementation. There were greater changes in the levels of AA and/or EPA in platelet PL compared with the aorta PL, which might have accounted for the differential effects of these PUFA on thromboxane production compared with PGI₂ production in this study.