Effect of androgens on serum lipids and lipoproteins

The effects of androgens on lipid transport and metabolism have been reviewed. These effects are probably independent of the androgenic and anabolic activities of the androgens, although the molecular mechanism of action is still not known. Presumably the lowering by androgens of the concentrations of serum lipids and lipoproteins could be the consequence possibly of a primary, inhibitory effect on the synthesis of apolipoprotein A. In addition the role of increased lipolytic activities in plasma and of effects on intermediatry metabolism has been considered. Special Fellowship Awardee (1F11 NSO2245-01) from the National Institute of Neurological Diseases and Stroke One of eight papers presented at the symposium “Recent Advances in Drugs Affecting Lipid Metabolism,” AOCS Meeting, Houston, May 1971.     

The distribution of dietary plant sterols in serum lipoproteins and liver subcellular fractions of rats

Rats were fed plant sterols containing campesterol and β-sitosterol in the different proportions, and their distribution in serum lipoproteins and in liver subcellular fractions was determined. In serum lipoproteins, the percentage as well as the concentration of plant sterols increased with the increase in the density of lipoproteins. Thus, high density lipoprotein (HDL) contained the highest and very low density lipoprotein (VLDL), the lowest. Also, there were distinct differences in the ratio of campesterol to sitosterol among lipoproteins, it was the highest in VLDL and lowest in HDL. Quantitatively, more than 75% of campesterol and 80% of sitosterol were carried in HDL; the values were significantly different from those of cholesterol (ca. 70%) in relation to total cholesterol. The distribution of plant sterols in liver subcellular fractions was virtually the same with that of cholesterol. Both nuclei and microsomes contained approximately 40% of total plant stetols. A preliminary part of the study was presented at the First Congress of the Federation of Asian and Oceanian Biochemists in Nagoya, October 1977.     

The influence of protein and carbohydrate type on serum and liver lipids and lipoprotein cholesterol in rabbits

The non-lipid portions of semi-synthetic diets appear to be important determinants of hypercholesterolemia and atherosclerosis in the rabbit. Serum and liver lipid concentrations were determined in rabbits which had been pair-fed various protein (casein or soy protein isolate) and carbohydrate (sucrose or dextrose) sources as part of low fat, low cholesterol, semi-synthetic diets. It was verified that caseincontaining diets render rabbits hypercholesterolemic, while soy protein caused a degree of hypocholesterolemia. Additionally, sucrose, when fed in conjunction with casein, appears to augment this hypercholesterolemic effect. The distribution of total cholesterol among lipoprotein subclasses was increased in both the intermediate density lipoprotein (IDL) (1.006–1.019 g/ml) and low density lipoprotein (LDL) (1.019–1.063 g/ml) fractions and decreased in the high density lipoprotein (HDL) (1.063–1.21 g/ml) fraction when casein is fed. Soy protein feeding caused relatively more cholesterol to appear only in the IDL fraction when compared with commercial chow fed rabbits. Reasons for these differences may involve the saturation or suppression of endogenous lipoprotein hepatic receptors.     

Effect of ingestion of isomeric fatty acids on cholesterol and lipids of serum and liver

The effect of the ingestion of large amounts of thetrans, trans isomer of linolein upon the cholesterol and lipid levels of the blood and liver was investigated using hypercholesterolemic rats. The serum levels of esterified fatty acids and cholesterol of rats fed the diets containing 30% oftrans, trans linoleic acid glycerides and safflower oil were 15 and 25%, respectively, lower than those fed coconut oil. However, a weight loss associated with less intake of thetrans isomer as compared with a gain with the other two fats must be considered. The serum levels of labeled cholesterol of rats administered radioactive cholesterol along with thetrans isomer were intermediate in maximum value as compared to the levels obtained with coconut and safflower oils. These results suggest that thetrans isomers are not as effective as thecis isomers in lowering the cholesterol and lipids of the blood. The livers of the former group had a lower fat content than the latter which might be accounted for in part by the lower fat intake Presented at AOCS Meeting, Houston, Texas, 1965.     

Studies on lipid biosynthesis and cholesterol content of liver and serum lipoproteins in rats fed various phthalate esters

The effect of various phthalate ester plasticizers on lipid metabolism in rats was studied in vivo and in vitro. Di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DBP) inhibited (30–70%) hepatic sterologenesis from¹⁴C-acetate and¹⁴C-mevalonate in liver minces from rats fed the phthalates at a level of 2.5 mmoles/100 g of chow diet for 21 days; inhibition of¹⁴C-acetate incorporation into phospholipids, triglycerides, and steryl esters was reduced (35–70%) by DEHP and DBP feeding. In addition, serum cholesterol was lowered ca. 14 mg/dl with dietary DEHP or DBP but not with dimethyl phthalate (DMP). Hepatic total cholesterol levels were reduced significantly (31%, P<0.001) by DMP but not by DBP or DEHP. In other studies with DEHP fed at the 0.5% level in chow diets (1.3 mmoles/100 g), the incorporation (esterification) of³H-oleate into di- and triglycerides was reduced ca. 40%. Furthermore, the addition of DEHP (2%, 5 mmoles/100 g) to a semisynthetic diet containing 10% fat (hydrogenated coconut oil) resulted in changes in serum lipoprotein composition. The percentage of serum cholesterol in LDL rose from 22% to 34% while that in HDL fell from 78% to 66%; these changes occurred without net changes in serum cholesterol levels. Possible mechanisms for the inhibitory effect of phthalates on hepatic lipid biosynthesis are discussed. These studies are in partial fulfillment of the requirements for a Doctorate degree in Medical Sciences, McMaster University, Hamilton, Ontario, Canada.     

The effect of cholesterol supplementation on glutamate-induced hypocholesterolemia in the Mongolian gerbil

The effect of cholesterol supplementation on the hypocholesterolemia induced by glutamic acid feeding has been studied in the Mongolian gerbil. Serum triglycerides and phospholipids and hepatic cholesterol and triglyceride contents have also been studied during the control and glutamate feeding. Cholesterol supplementation (0.05% and 1.0%) did not diminish the hypocholesterolemic response (20–24% decrease in serum cholesterol). The glutamate amino acid formula diet caused no change in serum triglyceride, serum phospholipid, hepatic cholesterol and hepatic triglyceride content when compared to the control formula diet. No lesions of the hypothalamic or paraventricular areas of the brain were noted on histological preparation in adult gerbils given large amounts of glutamic acid orally.     

Interaction between dietary proteins and lipids in the regulation of serum and liver lipids in the rabbit. Effect of fish protein

Purified diets varying in dietary protein, namely casein (CA), soy protein (SP), fish protein (FP), and lipid origin (corn oil (CN), coconut oil (CO)) were fed to rabbits to evaluate the effects of protein and fat source, as well as protein-lipid interactions, on serum total, lipoprotein and hepatic lipid levels. Dietary proteins and lipids exerted a separate effect on serum total cholesterol (C), very low-density lipoprotein cholesterol (VLDL-C), and low-density lipoprotein cholesterol to high density lipoprotein cholesterol (LDL-C/HDL-C) ratio. Hence, CA increased serum cholesterol compared to SP, while coconut oil enhanced serum and VLDL-C, and decreased LDL-C/HDL-C compared to corn oil. Dietary proteins interacted with dietary lipids to modulate HDL-C levels. Thus, FP maintained a high level of HDL-C regardless of lipid origin, compared to CA and SP whose HDL-C levels were decreased by corn oil, compared to coconut oil. A dietary protein-lipid interaction was also observed in the regulation of liver cholesterol levels. Coconut oil, compared to corn oil, decreased liver cholesterol in rabbits fed FP, whereas hepatic cholesterol concentration was unaltered by dietary lipid source in CA- and SP-fed rabbits. These results demonstrate that dietary proteins act synergistically with dietary lipids to regulate cholesterol metabolism in the rabbit. This work was presented in part at the 74th Annual FASEB meeting held in Washington, D.C., April 1–5, 1990.     

The effect of dietary sterculic acid on the hepatic lipids of rainbow trout

Groups of young rainbow trout (5 g) were fed a basal diet containing 9% salmon oil and 1% tristearin with 0, 100 or 200 ppm methyl sterculate. Liver lipids were separated into polar and nonpolar fractions and the fatty acids quantitatively analyzed. Significant elevations of the stearic-oleic and the palmiticpalmitoleic ratios were found in liver fatty acid composition 10 days after the feeding trial began. Liver triglycerides of fish fed methyl sterculate for 87 days contained only 2–3% docosahexenoic acid as compared to 10.69% in control trout, suggesting an effect on the biosynthesis of long chain polyunsaturates. Dietary cyclopropenoid fatty acids (CPFA) suppressed growth rate during the first part of the 200 day feeding trial. After 90 days no differences in the rate of weight gain were observed between the control and CPFA groups. A seven day feeding trial with 0, 5, 20, 50 and 100 ppm CPFA resulted in a maximum change in the stearic-oleic ratio at 50 and 100 ppm levels. All levels of CPFA increased this ratio and caused marked alterations in the cellular morphology of the liver. Presented in part at the annual meeting of the Federation of American Societies for Experimental Biology, Atlantic City, New Jersey, April, 1968. Technical Paper No. 2565, Oregon Agricultural Experimental Station.     

Effect of dietary cholesterol protected against ruminal hydrogenation on the plasma cholesterol and liver of sheep

Dietary supplements containing cholesterol or sunflower oil were prepared to protect them against degradation in the rumen. On feeding daily supplements containing 1–2 g protected cholesterol and/or 100g protected sunflower oil to sheep, along with a basal ration of crushed oat grain and lucerne chaff, a rise in the plasma cholesterol was observed when compared with control animals. Livers from sheep fed protected cholesterol were enlarged, friable and cirrhotic in appearance and contained large deposits of esterified and free cholesterol, while livers from animals fed protected sunflower oil alone contained much less cholesterol. Octadecenoates constituted the major fatty acids in cholesterol esters, which, in animals fed protected sunflower oil, were mainly polyunsaturated. The factors involved in the deposition of liver lipid at very low dietary cholesterol concentrations (0.11–22%) in sheep compared with monogastric animals are discussed. Deceased.     

Influence of dietary egg and soybean phospholipids and triacylglycerols on human serum lipoproteins

The online version of the original article can be found at     

Influence of dietary egg and soybean phospholipids and triacylglycerols on human serum lipoproteins

Human serum lipid and lipoprotein concentrations and compositions were compared in ten healthy middle-aged men consuming phospholipids from egg or from soybean or triacylglycerol mixtures with fatty acid compositions similar to those of the phospholipids. All subjects followed each of the four treatments: egg phospholipids (EP), soybean phospholipids (SP), an oil of fatty acid composition similar to that of EP, and an oil similar in fatty acid composition to SP for six weeks with “wash-out” periods of similar duration between treatment periods. The phospholipids, 15 g/d, and the oils, 12 g/d, which contained approximately equivalent quantities of fatty acids were provided to the subjects in gelatin capsules and were taken before meals. Diet intake was monitored by three-day food records. Serum lipoproteins (L_p) were separated by ultracentrifugation into very low density lipoproteins, low density lipoproteins (LDL), high density lipoproteins (HDL)₂ and HDL₃. L_p fractions and whole serum were analyzed for triacylglycerols, cholesterol (CH), phospholipids (PL), and protein. HDL cholesterol was determined in while serum. Cholesteryl esters were determined in some L_p fractions. Lipid compositions of L_p were expressed in mmol/g protein. Apoprotein B was measured in whole serum and in LDL; apoprotein A-I in whole serum and in HDL₃. In whole serum, CH and PL were significantly lower after the SP compared to EP treatment periods. CH, but not PL, was lower after SPTG compared to EP. CH in HDL₂ was significantly higher after SP compared to SPTG. Also, PL in HDL₂ were significantly higher after SP compared to all other treatments and to baseline. Although human serum lipid responses to dietary phospholipids were generally the same as responses to ingested oils of comparable fatty acid composition, the data suggest the possibility that SP selectively increase HDL₂ cholesterol and phospholipids.     

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.     

Influence of dietary fat and protein on serum cholesterol of cholesterol-fed chicks

Summary Cottonseed oil, partially hydrogenated cottonseed oil and corn oil, were fed at 4% and 10% of the diets with two levels of protein, 19% and 25%, and with 0.5% cholesterol to cockerels 21 days of age for a period of 38 days. Blood samples were obtained at 0, 14, 24, and 38 daysvia heart puncture. The data indicate that the serum cholesterol value, irrespective of the level or type of fat, was significantly lower in those groups of birds which were fed the higher level of protein. Excluding the combination of 19% protein and 10% cottonseed oil, the degree of saturation did not have any apparent effect upon serum cholesterol because the mean differences among the oils and between the fat levels were not statistically significant.     

Effect of cupric ions on serum and liver cholesterol metabolism

Cupric ions were administered subcutaneously to male Sprague-Dawley rats at a single dose of 200 μmol/kg. At 24 hr after administration, a remarkable increase of total and free cholesterol was seen in the rat serum. Also, when lecithin-cholesterol acyltransferase (LCAT) (E.C. 2.3.1.43) activity was expressed as the percentage of the total serum that free cholesterol esterified, the acyltransferase activity in rats treated with cupric ions showed a slight decrease while the triglyceride content in rat serum and liver decreased by 54% and 61%, respectively. However, the content of hepatic cholesterol in rats treated with cupric ions did not show such a marked change. On the other hand, acid cholesteryl ester hydrolase activity (Acid CEH) (E.C. 3.1.1.14) in liver lysosomes of rats treated with cupric ions showed a marked decrease with increasing cupric ion concentration both in vivo and in vitro. Furthermore, cupric ions caused a marked release of the lysosomal enzymes cathepsin D and β-glucuronidase into the cytosolic fraction. The changes in acid cholesteryl ester hydrolase activity induced by cupric ions appear to be a direct effect of cupric ions on the enzyme. These results suggest that excessive cupric ion concentrations could cause various disorders in lipid metabolism.     

The interaction of prostaglandin E1 with serum lipoproteins possible role in cholesterol homeostasis

Prostaglandin (PG) E₁ significantly stimulates the rate of cholesterol esterification in plasma. This effect could be attributed to an enhancement by PGE₁ of the interlipoprotein transfer of phosphatidylcholine and cholesteryl esters,i.e., the substrate and product of lecithin-cholesterol acyltransferase (LCAT). The enhancement effect appears to be due to a rearrangement of the lipoprotein surface induced by specific interaction of PGE₁ with some apolipoproteins, although the binding capacity of serum lipoproteins for PGE₁ was found to be rather weak. To explain these findings, an hypothetical non-equilibrium model was put forward. The purpose of the present article is to summarize available data on the PGE₁-lipoprotein interaction.     

The effect of dietary docosahexaenoic acid on plasma lipoproteins and tissue fatty acid composition in humans

Normal, healthy male volunteers (n=6) were fed diets [high docosahexaenoic acid-DHA] containing 6 g/d of DHA for 90 d. The stabilization (low-DHA) diet contained less than 50 mg/d of DHA. A control group (n=4) remained on the low-DHA diet for the duration of the study (120 d). Blood samples were drawn on study days 30 (end of the stabilization period), 75 (midpoint of the intervention period), and 120 (end of the intervention period). Adipose tissue (AT) samples were taken on days 30 and 120. The plasma cholesterol (C), low density lipoprotein (LDL)-C and apolipoproteins (apo) [Al, B, and lipoprotein (a)] were unchanged after 90 d, but the triglycerides (TAG) were reduced from a mean value of 76.67±24.32 to 63.83±16.99 mg/dL (n=6, P<0.007 using a paired t-test) and the high density lipoprotein (HDL)-C increased from 34.83±4.38 mg/dL to 37.83±3.32 mg/dL (n=6, P<0.017 using a paired t-test). The control group showed no significant reduction in plasma TAG levels. Apo-E, however, showed a marked increase in the volunteers’ plasma after 90 d on the high-DHA diet, from 7.06±4.47 mg/dL on study day 30 to 12.01±4.96 mg/dL on study day 120 (P<0.002 using a paired t-test). The control subjects showed no significant change in the apo-E in their plasma (8.46±2.90 on day 30 vs. 8.59±2.97 on day 120). The weight percentage of plasma DHA rose from 1.83±0.22 to 8.12±0.76 after 90 d on the high-DHA diet. Although these volunteers were eating a diet free of eicosapentaenoic acid (EPA), plasma EPA levels rose from 0.38±0.05 to 3.39±0.52 (wt%) after consuming the high-DHA diet. The fatty acid composition of plasma lipid fractions—cholesterol esters, TAG, and phospholipid—showed marked similarity in the enrichment of DHA, about 10%, after the subjects consumed the high-DHA diet. The DHA content of these plasma lipid fractions varied from less than 1% (TAG) to 3.5% (phospholipids) at baseline, study day 30. EPA also increased in all plasma lipid fractions after the subjects consumed the high-DHA diet. There were no changes in the plasma DHA or EPA levels in the control group. Consumption of DHA also caused an increase in AT levels of DHA, from 0.10±0.02 to 0.31±0.07 (wt%) (n=6, P<0.001 using a paired t-test), but the amount of EPA in their AT did not change. Thus, dietary DHA will lower plasma TAG without EPA, and DHA is retroconverted to EPA in significant amounts. Dietary DHA appears to enhance apo-E synthesis in the liver. It appears that DHA can be a safe and perhaps beneficial supplement to human diets.     

Effects of diets rich in saturated fatty acids with or without added cholesterol on plasma lipids and lipoproteins

Semi-synthetic diet I which contained 16% hydrogenated coconut oil and 5% cholesterol, and diet II, identical to I but without cholesterol supplement, were fed to dogs for four months to determine the effects of added cholesterol on lipemia produced by diets high in saturated fatty acids (FA) and lacking essential FA. In addition, diet I was fed to another group of dogs for 12 to 16 months. The initiation of lipemia was very similar in all experimental animals. Plasma from dogs on diets I and II showed significant increases in lipid concentration and changes in FA per cent composition within the first week, as compared to controls, while during the first month there was no difference in lipid concentration or FA distribution in all lipid fractions between I and II. At the 10th and 16th weeks plasma total and free cholesterol and phospholipid were significantly higher in the group on diet I, with the cholesterol supplement, than on diet II with no added cholesterol, but there was no difference in triglyceride concentration between these groups. Dogs on diet I for 12 to 16 months showed a further and substantial increase in plasma FA concentration; these changes were most marked in cholesteryl esters. Little or no lipoprotein with electrophoretic and ultracentrifugal properties of alpha-lipoprotein was present in the plasma. Immunotechniques showed that it was present. The composition of dietary FA had great influence in producing this hyperlipemia. Lipemia produced was not a simple reflection of the FA in these diets as evidenced by the increase in some FA, e.g., C_16∶1, which was absent in the experimental diets and C_18∶1, which contributed only 3.4% of the FA. Large increases in palmitoleate and oleate indicate synthesis or mobilization or both from other tissues. Diets composed predominantly of saturated medium chain length fatty acids, with or without added cholesterol were equally effective in the initiation of hyperlipemia. Data also suggest that added cholesterol is necessary for sustaining hyperlipemia. Presented in part at the AOCS Annual Meeting, New Orleans, April 1970.