The effect of a histidine-excess diet on cholesterol synthesis and degradation in rats

Feeding a diet high in excess histidine (5% L-histidine) resulted in hypercholesterolemia and enlargement of the liver in rats. To clarify the mechanism of the hypercho-lesterolemia cholesterol synthesis and degradation were followed. We found that hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in histidine-excess diet rats was significantly higher than in rats fed a basal diet. Incorporation of [³H]water into cholesterol of liver slices from rats fed the histidine-excess diet was higher than incorporation into liver slices from rats fed the basal diet (expressed per liver per 100 g body weight).In vivo incorporation of [³H]water into hepatic cholesterol was also higher, but the incorporation into cholesterol of the small intestine was lower in histidine-fed rats than in rats fed the basal diet (expressed per liver per 100 g body weight). Hepatic cholesterol 7α-hydroxylase activity was similar in both groups. The data suggest that the hypercholester-olemia caused by histidine-excess diet appears to be due to the stimulation of cholesterol synthesis in the liver.     

The effect of dietary supplementation of cholesterol and its subsequent withdrawal on the liver lipids and serum lipoproteins of chickens

Two groups of male chickens were fed either a control diet (group N) containing a standard poultry ration admixed with 10% corn oil or a cholesterol diet (group C) in which the control diet was supplemented with 1% cholesterol. After 6 weeks on the diets, a negligible amount of very low density lipoprotein (VLDL) was found in the serum from control animals. On the other hand, the serum VLDL from the cholesterol-fed birds was the predominant lipoprotein and carried 72% of the total serum lipids. Surprisingly this lipoprotein from cholesterol-fed animals was very low in triglycrides (6%) and high in total cholesterol (77%). While the level of serum low density liporotein was unaffected by the ingestion of cholesterol, the concentration of total lipids and phospholipids in the high density lipoprotein decreased in cholesterol-fed animals. The greatest change in liver lipids from animals fed cholesterol was found in the cholesterol esters, whereas the unesterified cholesterol, triglyceride and phospholipid varied slightly or remained constant. In normal animals the distribution of cholesterol between the liver and the serum was about equal, whereas in the cholesterol-fed birds the liver accounted for 80% of the cholesterol found in the liver-serum pool. In order to determine how the hypercholesterolemic bird responds to the withdrawal of cholesterol from the ration, a diet-exchange experiment was conducted. In this study the birds that were originally fed the cholesterol diets (group C) for 6 weeks were placed on the control diet (group CN) and the birds fed the control diet (group N) for 6 weeks were given the cholesterol diet (group NC). At periodic intervals, 1, 3, 7 and 14 days following the change of diets, 3–5 animals from each group were sacrificed, and analyses performed on their serum lipoproteins and liver lipids. Within one day after the diet substitution, there was a 31-fold increase and a 46% decrease, respectively, in the serum VLDL concentration in groups NC and CN as compared with their corresponding steady state values (groups N and group C, respectively). The liver cholesterol increased 4-fold and decreased 40%, respectively, in the two groups NC and CN as compared with the values obtained before the diet substitution. It is suggested that the concentration of cholesterol in the liver is the principal factor controlling cholesterol metabolism in chickens fed a hypercholesterolemic diet. This represents a portion of a Ph.D. thesis submitted by A.W. Kruski to the University of Illinois in February 1971.     

Vitamin A induced hypertriglyceridemia in cholesterol-fed rats

The effects of level and feeding frequency of retinoic acid (OIC) or retinyl acetate (YL) on the accumulation of lipids in the serum and liver of rats were investigated. Male Sprague-Dawley rats were fed ad libitum 1% cholesterol diets with or without supplemental OIC or YL. Vitamin A-fed groups included (per g of dry diet): 105 μg of OIC or 113 μg YL daily for 28 days, 735 μg OIC or 791 μg YL once each week for 28 days; and 735 or 105 μg OIC on day 1 or 105 μg OIC daily for the week experiment. Daily feeding of OIC or YL increased serum triglyceride concentrations as compared to controls. Several days after removal of OIC or 1 week after removal of supplemental YL from the rat diets, serum triglyceride concentrations returned to basal levels. Cholesterol feeding elevated serum cholesterol as well as hepatic cholesterol, total lipids and vitamin A concentrations. Daily OIC feeding depressed serum and hepatic cholesterol concentrations. These results show that daily supplement of vitamin A increased serum triglycerides and reduced serum and hepatic cholesterol concentrations. Serum and liver alterations were dependent on continued feeding. Presented in part at the Federation of American Society for Experimental Biology, Chicago, 1977 (Abst. No. 4576).     

Sources of triacylglycerol accumulation in livers of rats fed a cholesterol-supplemented diet

The source of free fatty acids (FFA) and the pathways contributing to the accumulation of neutral fats in livers of rats fed a cholesterol-enriched diet were investigated in this report. Supplementation with 1% cholesterol in the diet for four weeks resulted in hepatomegaly in the rats. The contents of cholesterol and triacylglycerols (TG) per gram liver measured in rats fasted overnight increased by 48 mg (∼tenfold) and 66 mg (∼fourfold), respectively. The activities of glycerophosphate acyltransferase and diacylglycerol acyltransferase, the two key enzymes for TG synthesis in liver microsomes, were found to increase by 23 and 19%, respectively, in the cholesterol-fed rats. The secretion of plasma TG present predominantly in very low density lipoprotein was found to decrease by ∼30%. The incorporation of tritium from tritiated water in liver FFA increased by twofold in rats fed the cholesterol-supplemented diet, whereas the activity of CPT I in liver mitochondria decreased by 23%. The uptake of plasma FFAin vivo in livers of fasted rats maintained on the cholesterol-supplemented diet decreased by 60%. Our data thus indicate that the excess TG accumulated in livers of rats fed the cholesterol-enriched diet resulted from increased synthesis and decreased secretion of TG. To meet the demand of fatty acids for this purpose,de novo lipogenesis increased, whereas β-oxidation decreased. Although difference in the uptake of extrahepatic FFA may be discounted, a difference in the uptake of chylomicron remnants between the control and cholesterol-fed rats may not be ruled out.     

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.     

The effect of prolonged fasting and of glucose refeeding on rat serum and liver lipid levels

The effects upon serum lipids of prolonged fasting of rats followed by refeeding with glucose or chow was studied. Fasting caused a decrease in the levels of serum triglyceride, phospholipid and cholesterol ester, while the level of total cholesterol remained unchanged. Refeeding 20% glucose in water for one day after three days of fasting caused a significantly greater decrease in serum lipid levels than did an additional day of fasting, while refeeding chow for one day restored the serum lipid levels to normal. Seven days of fasting or one day of glucose refeeding following three days of starvation resulted in almost complete disappearance of all serum lipoprotein bands on paper electrophoresis. After four days of refeeding glucose to rats previously fasted for three days the serum lipid levels and lipoprotein patterns approached those seen in fed animals. Serum free fatty acids increased upon fasting, but after seven days of starvation their concentration dropped to that observed in the fed rats. Refeeding for one day with glucose or chow reduced the serum free fatty acid concentration to less than half of the starvation levels. Four days of starvation caused a great decrease in liver weight without causing very pronounced changes in the content of phospholipid and triglyceride in the whole liver; the cholesterol content, notably esterified cholesterol, decreased. Glucose feeding for one day after three days of starvation, while increasing liver weight, did not cause any appreciable change in the hepatic lipid content. Following the three days of starvation lipogenesis from glucose by liver slices is restored to the same extent by refeeding glucose or chow for one day. The role of liver, adipose tissue and diet in supplying fatty acids for serum lipids following fasting is discussed.     

Liver and serum lipids and lipoproteins of rats fed 5% L-lysine

Soybean protein and casein supplemented with 1% Arg were compared for their ability to prevent fatty livers caused by excess dietary Lys. The concentrations of serum lipids and lipoproteins of rats fed 5% Lys and having vatty livers were also compared with those of rats fed the identical diet but lacking fatty livers when killed. The total liver lipids, triglycerides and cholesterol of rats fed 15% casein +5% Lys were 3.9, 12.4 and 2 times control values, respectively. Rats fed 5% Lys +1% Arg or 5% Lys with 15% soybean protein had liver lipid concentrations similar to controls fed no supplemental Lys. Serum total lipids, triglycerides, cholesterol, phospholipids and free fatty acids also did not change, and serum ketone bodies were slightly elevated with Lys feeding whether the rats had fatty livers or not. The concentrations of circulating HDL were slightly depressed in all rats fed 5% Lys while LDL were significantly elevated, particularly in rats without fatty livers. Serum VLDL did not change with 5% dietary Lys. Overall, excessive dietary Lys caused fatty livers which were prevented by varying the diet or length of feeding. Excess Lys feeding altered lipoprotein metabolism shown by decreased serum HDL and a substantial elevation in LDL. The latter was more apparent when the fat accumulation in liver was less severe or absent. The data suggest that the fatty liver from Lys excess is probably unrelated to increased fat mobilization from storage, decreased fat oxidation or to a major block in the transport of triglycerides from the liver to the circulation.     

Dietary fat effect on incorporation and release of lipids and cholesterol by rat intestinal slices

The effect of saturated and unsaturated fats on in vitro formation and release of lipids and cholesterol from¹⁴C acetate by rat intestinal tissue was investigated. The rats were fed a basal diet enriched with either 25% corn oil or lard and then sacrificed after a 10- or 25-day feeding period. It was observed that a similar¹⁴C lipid content but a greater¹⁴C cholesterol content was found in the intestinal tissue of rats fed corn oil than in rats fed lard for 10 days. After a longer period of feeding of 25 days, the intestinal tissue¹⁴C cholesterol level was decreased in the corn oil fed rats without any significant effect on other lipids. These data suggest that corn oil in some way influences cholesterol biosynthesis depending upon its degree of unsaturation and the period of time for which it is fed. The decrease at the later time might involve some mechanism which aids in getting rid of accumulated tissue cholesterol. Less¹⁴C lipid and¹⁴C cholesterol were released by the intestinal tissue of rats fed the unsaturated fat as compared with those fed the saturated fat, suggesting a possible role in vivo in reducing blood lipids and blood cholesterol levels. Robert A. Welch Foundation.     

Deposition of dietary epoxides in tissues of rats

Epididymal fat pad lipids from rats fed trivernolin at the 4.8% level in the diet for 90 days were found to contain 6.1% epoxyoleic acid. No epoxides were detected in the serum lipids and only trace amounts were found in the liver lipids. TLC, GLC and a specific color reaction with picric acid were used to identify this fatty epoxide in the tissues. Epoxyoleic acid was shown to be present as a mixture of predominately monovernoloyl triglycerides with some divernoloyl triglycerides and small amounts of trivernolin. Lipase hydrolysis of the first two triglycerides has demonstrated that the vernoloyl groups are present mostly in the 1,3 positions. In a separate experiment, rats were fed cholesterol epoxide at the 0.5% and 1.5% levels in the diet for 90 days. TLC and GLC examination of lipids from these rats failed to reveal the presence of any cholesterol epoxide. Only one-half of the sterol fed could be accounted for in the fecal lipids. Presented in part at the AOCS Meeting, Chicago, October 1967.     

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.     

Effect of cocaine intake on the development of fatty liver in rats fed a low-protein diet

It has been shown that cocaine given in the diet is able to reduce fat accumulation in the liver of protein-malnourished rats (Arch. Latinoamer. Nutr. 19: 69-79, 1969). This study was, therefore, designed to approach the probable action of the drug upon the process (increased triglycerides synthesis and normal/decreased capacity for exporting triglycerides from the liver into the blood) which leads to an increased fat accumulation in the liver under this physiological condition. To accomplish this purpose, the total and fractioned lipids in the liver and total lipids as well as lipoproteins in serum were determined in female Wistar rats (120-130 g) fed either a 5% corn protein diet or a 20% casein diet, with and without cocaine (15 mg HCl cocaine/10 g of diet) for 18 days. The results, aside from confirming the reduction (p less than 0.001) of fat accumulation in the liver of rats fed on the 5% corn protein diet plus cocaine, revealed that this drug also reduced triglycerides concentration (significantly, (p less than 0.001, when results were calculated by difference, and slightly reduced them when results were determined) in this tissue. Nevertheless, it increases both total lipids (p less than 0.05) and triglycerides-rich pre-beta lipoprotein (p less than 0.10) levels in the serum of these animals. Otherwise, these lipidic parameters were not modified by cocaine in rats on the 20% casein diet, except for the total cholesterol level in liver and the cholesterol-rich beta lipoprotein level in serum. Respectively, these were slightly and significantly (p less than 0.001) reduced by the drug. These evidences and their statistical significance suggest that cocaine given chronically with the 5% corn-protein diet for 18 days, reduces at least partially (other biochemical event in the liver could have also accounted for its effect at this level) the liver fat accumulation, by increasing the triglycerides output from the liver into the blood. Elsewhere, cocaine appears to be able to induce some metabolic alterations in the hepatic cholesterol of well-nourished rats.     

Effect of garlic (Allium sativum linn) on serum lipoproteins and lipoprotein cholesterol levels in albino rats rendered hypercholesteremic by feeding cholesterol

The hypocholesteremic activity of garlic was tested by incorporating freeze-dried garlic powder at 0.5, 1.0, 2.0 and 3.0% levels in an atherogenic diet fed to rats. It was observed that 0.5 and 1.0% levels were not effective whereas the other 2 levels were. The group fed 2.0% garlic powder had much lower serum cholesterol level than the one fed 3%. The increased levels of low density lipoproteins (LDL) and LDL-cholesterol in rats fed the atherogenic diet were partly reversed in rats receiving a supplement of 2% garlic powder. On a cholesterol-containing diet, high density lipoproteins (HDL) and HDL-cholesterol levels were decreased. Inclusion of garlic powder in the atherogenic diet enhanced the percentage of HDL whereas no change was observed in HDL cholesterol levels. Commercial garlic pearls (equivalent to 0.15% garlic powder in the diet) produced a significant decrease in serum and liver cholesterol levels in rats fed the atherogenic diet. On the other hand, asafoetida at 1.5% level failed to reduce the serum cholesterol levels in the cholesterol-fed rats.     

Stimulation of lipid absorption in young rats by cholesterol: Early time changes and effects on pentobarbital sleeping time

Four groups of young male and female rats were fed a chow diet (0), chow plus 10% corn oil (F), chow plus 1% cholesterol (C), or chow plus 1% cholesterol plus 10% corn oil (CF) for 1, 2, 4 and 8 days. After 2 dats, male F, C and CF rats exhibited a shorter anesthesia period (−20 to −30%) when given pentobarbital. By 4 days, male F and C rats had pentobarbital sleeping times (PB-ST) 20% less than 0 rats. These effects were additive and CF rats had 40% shorter PB-ST. Reduction of PB-ST by cholesterol and corn oil was similar but slightly less in female rats. Liver lipid content doubled in 4 days in CF rats, and liver cholesterol was 4 times that of 0 rats. These changes and the increases in metabolism of barbiturate suggested changes in liver microsomal enzyme activities. Serum glutamic oxaloacetic and glutamic pyruvic transaminase, two enzymes reflective of liver damage, did not increase after 8 days on C, F or CF diets. Our results suggest that consumption of an animal sterol and a high lipid diet by laboratory rats, normally consuming a diet low in fat (3–4%), increases the ability of the animal to detoxify a barbiturate. Storage of absorbed dietary cholesterol in the liver may represent a major mechanism for maintaining extra hepatic cholesterol homeostasis.     

The hypolipidemic effect of calcium-containing compounds and vitamin D2 in the rat

Two per cent dietary calcium carbonate alone (Group 1), in combination with vitamin D₂ (Group 2) or oyster shell calcium with vitamin D₂ (Group 3), was added to an atherogenic diet containing 20% fat and 2% cholesterol and fed to adult male Holtzman strain rats to evaluate the hypolipidemic effects of these supplements. A control group received the same diet, but the calcium was replaced by sand. After 21 days the serum cholesterol concentrations were lower by 35, 27 and 22%, respectively, in experimental groups 1, 2 and 3, compared to the controls. Serum triglyceride concentrations were lower by 10% in experimental groups 1, 2 and 3, compared to the controls. Serum triglyceride concentrations were lower by 10% in groups 1 and 2, and 17% in group 3. Concomitant with these decreases in serum lipids, there were increases in fecal 3-β-hydroxy-5-ene sterol, total glyceride and free fatty acid excretion. Serum calcium was elevated in the rats fed diets containing calcium when compared with the controls, whereas serum magnesium was depressed in thesy animals. Less calcium was excreted in the feces of rats fed calcium carbonate in combination with vitamin D than in those fed calcium carbonate. The results indicate a possible means of simultaneously treating both calcium deficiency and hyperlipidemia with a single agent.     

Serum lipids in suckling and post-weanling iron-deficient rats

Serum lipids were studied in iron-deficient and control rats during suckling and after weaning at 21, 30, and 60 days of age. Diets providing 5 or 307 ppm iron were fed to dams and their offspring during gestation, lactation, and after weaning. Rats on the deficient diet throughout the experimental period developed a hyperlipidemia characterized by elevated triglycerides, cholesterol, and phospholipids which was present at 21, 30, and 60 days. Control pups weaned to the deficient diet developed anemia at 30 days of age and hypertriglyceridemia at 60 days of age. Repletion of deficient rats with iron after weaning caused a rapid decline in serum lipid levels after only 9 days on the control diet. The hyperlipidemia of iron deficiency thus appears to be reversible with iron supplementation. The time required to develop hypertriglyceridemia in iron deficiency is longer postweaning than during suckling.     

Effects of dietary n−3 fatty acid-enriched chicken eggs on plasma and tissue cholesterol and fatty acid composition of rats

The purpose of this study was to examine the effects of feeding n−3 polyunsaturated fatty acid (PUFA)-enriched chicken eggs on plasma and liver cholesterol levels and fatty acid composition in rats. Eggs were collected from laying hens fed diets containing 10% flax seed (Hn−3), 12% sunflower seed (Hn−6), or wheat and soybean meal control (CON). Yolk powders were prepared and fed at the 15% level to weanling female Sprague-Dawley rats for 28 days. Consumption of n−3 PUFA-enriched yolks significantly reduced both plasma and liver total cholesterol. Liver total lipids and phospholipids of rats fed Hn−3 diet were enriched with linolenic, eicosapentaenoic, and docosahexaenoic acids with a concomitant reduction of arachidonic acid in liver phospholipids. The plasma cholesterol of rats fed yolk powders enriched with n−6 PUFA (mainly linoleic acid) was reduced to the same extent as in those fed the n−3 enriched, but the liver cholesterol was significantly increased, indicating differential effects of dietary n−3 and n−6 PUFA. The results demonstrated that the cholesterolemic and tissue lipid modulating properties of chicken eggs could be modified in a favorable way by altering the fatty acid composition of yolk lipids through manipulation of laying hen diets.     

Effects of dietary defatted squid on cholesterol metabolism and hepatic lipogenesis in rats

Male Sprague-Dawley rats were fed a cholesterol-free (Exp. 1) or cholesterol-supplemented (Exp. 2) diet containing 20% casein (control group) or 15% defatted squid and 5% casein (defatted squid group), as protein, for 14 d. Serum and hepatic cholesterol concentrations were lower in rats fed defatted squid than in those fed casein in both cholesterol-free (−20%, P<0.05 and −15%, P<0.05, respectively) and cholesterol-supplemented (−25%, P<0.05 and −15%, P<0.05, respectively) diets. Hepatic triglyceride concentration was lower in the defatted squid than in the control groups in both cholesterol-free (−51%, P<0.05) and cholesterol-supplemented diets (−38%, P<0.01). The activities of cytosolic fatty acid synthase and the NADPH-generating enzymes, malic enzyme and glucose-6-phosphate dehydrogenase, in the liver were lower in the defatted squid than in the control groups in both cholesterol-free (−21%, P<0.01, −33%, P<0.05, and −33%, P<0.01, respectively) and cholesterol-supplemented diets (−34%, P<0.05, −57%, P<0.05, and −67%, P<0.05, respectively). The activity of mitochondrial carnitine palmitoyltransferase in the liver was comparable between the control and defatted squid groups. The activity of Mg²⁺-dependent phosphatidate phosphohydrolase in the liver cytosol was lower in the defatted squid (−9%, P<0.05) than in the control groups only in the cholesterol-free diet. Fecal excretion of total steroids was stimulated by the feeding of defatted squid in both cholesterol-free (+77%, P<0.005) and cholesterol-supplemented diets (+29%, P<0.01). These results suggest that the nonlipid fraction of squid exerts a hypocholesterolemic effect by increasing the excretion of total steroids in feces. The fraction also induces a triglyceride-lowering activity in the liver by decreasing hepatic lipogenesis.     

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.     

Synthesis of cholesterol and total lipid by male and female rats fed beef tallow or corn oil

Male and female weanling rats were fed diets containing 2 or 42% of calories as corn oil or 40% as beef tallow plus 2% as corn oil until they were 12 or 18 weeks of age. Incorporation of C¹⁴-acetate into lipids of serum and liver and concentration of lipids in serum, liver, and carcass at the end of these periods were determined. Net synthesis of noncholesterol lipid was repressed by changing the diet from 2% to 42% of calories from either dietary fat in both sexes and at both ages. Cholesterol net synthesis was enhanced 29-fold in males and 22-fold in females fed 42% corn oil compared to 2% corn oil to the age of 12 weeks. It was enhanced only 2.6-fold for males and 3.4-fold for females by 40% beef tallow plus 2% corn oil. At 18 weeks of age cholesterol synthesis in males fed 42% corn oil was 7.3 and in females 9.1 times the value for those fed 2% corn oil. At this age the values for rats fed 40% beef tallow plus 2% corn oil were 1.2 and 3.7 times those for 2% corn oil fed rats of the respective sexes.     

Hypolipidemic activity of the surfactants aminimides,and their effects on lipid metabolism of rodents

A series of short chain fatty acid derivatives of aminimides were shown to possess hypolipidemic activity in rats and mice. Most of the agents tested lowered both serum cholesterol and triglyceride levels by at least 30% in mice and were effective in hyperlipidemic induced mice. 1,1-Dimethyl-1-(2-hydroxypropyl)-amine mersitimide lowered serum cholesterol levels 41% and serum triglyceride levels 56% at 20 mg/kg/day I.P. after 16 days. The same agent was active orally when administered to rats with a 38% reduction in serum cholesterol and a 52% reduction in serum triglycerides after 14 days. The agents inhibited liver acetyl CoA synthetase, ATP dependent citrate lyase and phosphatidate phosphohydrolase activities in vitro and in vivo. Reduction of cholesterol, triglycerides, neutral lipids and phospholipid levels were noted in the livers of mice treated for 16 days. In rat studies, cholesterol, triglyceride and phospholipid levels were reduced in liver, small intestine and the feces after two weeks' dosing. The cholesterol content was reduced in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions but elevated in the high density lipoproteins (HDL). Triglyceride levels were lowered in the VLDL, and neutral lipid levels were reduced in the chylomicron and VLDL fractions.