Testosterone & lipid metabolism in rabbits.

Testosterone and lipid metabolism was studied in rabbits. The effect of orchidectomy in rabbits fed normal diets and of testosterone propionate administration to these animals on total cholesterol, phospholipids, and triglycerides of serum, liver, aortic arch, thoracic aorta, and abdominal aorta as well as the activity of lipoprotein lipase in the aortic segments and heart was investigated. With a few exceptions, total cholesterol,phospholipids, and triglycerides increased in these tissues in orchidectomized animals and testosterone counteracted this increase. 3 segments of the aorta revealed variations in response to lipids in the orchidectomized animals as well as in the testosterone administered. Lipoprotein lipase activity decreased in the heart and the 3 aortic segments on orchidectomy, and testosterone administration caused increased enzyme activity.     

Effect of dehydration on lipid metabolism

Control of 25 sportsmen-wrestlers determined that accelerated loss in weight leads to a significant increase of ketone bodies evacuation with urine. The loss in weight for a 10-11 days period before a competition results in a less pronounced hyperketonuria. In experiment on rats it is shown that 48 and 98 hour hyperthermia and dehydration lead to the inhibition of the glucose-6-phosphate dehydrogenase activity in the liver. The mentioned permits supposing that under indicated conditions the inhibition of fat acid synthesis caused by NADPH2 and an increase of ketone bodies and cholesterol synthesis are observed.     

Effect of captopril on serum lipid levels and cardiac mitochondrial oxygen consumption in experimentally-induced hypercholesterolemia in rabbits

Angiotensin converting enzyme inhibitors are widely used in therapy of cardiovascular diseases. However, the consensus on effects of these inhibitors in control of myocardial oxygen consumption during the process of experimental hypercholesterolemia and under the condition of endothelial dysfunction has not been reached. Here we examined effects of captopril, an angiotensin converting enzyme inhibitor, on serum lipid levels and oxygen consumption rate in mitochondria isolated from heart of rabbits treated by hypercholesterolemic diet. During the twelve-week period, the Chinchilla male rabbits were daily treated by saline (controls); 1 % cholesterol diet; 5 mg/kg/day captopril or 1 % cholesterol + 5 mg/kg/day captopril. Total- and high-density lipoprotein cholesterol and triglyceride in serum were measured spectrophotometrically. The left ventricle mitochondrial fraction was isolated and myocardial oxygen consumption was measured by Biological Oxygen Monitor. Mitochondria isolated from hearts of rabbits exposed to hypercholesterolemic diet showed significantly reduced respiration rates (state 3 and state 4) with altering adenosine diphosphate/oxygen ratio, whereas the respiratory control ratio was not affected when compared to controls. Mitochondria from cholesterol/captopril-treated animals showed significantly reduced respiration rates without altering adenosine diphosphate/oxygen ratio index or respiratory control ratio. Although captopril did not exert the favorable effect on serum lipid levels in cholesterol-treated animals, it restored the mitochondrial oxygen consumption. Further studies should be performed to define the underlying physiological and/or pathophysiological mechanisms and clinical implications.     

Effect of chronic heparin administration on serum lipolytic activity and some aspects of lipid metabolism

Chronic heparin administration to rats for periods up to 8 days by i.p. implantation of mini pumps, increased serum total lipolytic activity in a dose-dependent manner up to infusion rates of 10 U/h per 100 g body weight. This augmentation was predominantly due to lipoprotein lipase (LPL). Synchronously, heart muscle demonstrated a dose-dependent reduction in LPL activity and adipose tissue showed a biphasic response, LPL activity decreasing at low doses and rising towards control levels at higher doses. Lipolytic activities of skeletal muscle and liver were unaffected. Increased serum LPL could not be attributed to altered enzyme clearance from the circulation in chronically heparinised rats, but was accompanied by a reduced response to i.v. high-dose heparin indicating reduction in the pool of endothelial-bound enzyme. Fasting serum concentrations of triacylglycerol and glycerol were unaffected in chronically heparinised animals although accelerated clearance of exogenous 14C-labelled VLDL was demonstrated, together with enhanced uptake of the isotope by liver and heart. Since de novo synthesis of fatty acids and triacylglycerol from 3H2O was not increased by heparin, we suggest that serum triacylglycerol concentrations were maintained by enhanced re-esterification of preformed fatty acids taken up by the liver. Hepatic cholesterol synthesis from 3H2O was augmented by heparin; this observation is consistent with reported increases in serum total and HDL-cholesterol mediated by chronic heparin administration in man and dog.     

Effect of Lipoprotein-X on lipid metabolism in rat kidney

Lipoprotein-X (Lp-X) is found in the plasma of patients with familiallecithin: cholesterol acyltransferase (LCAT) deficiency syndromes. Themajority of the patients with this disorder develop progressiveglomerulosclerosis. In this study, the effect of Lp-X on lipid metabolism inperfused rat kidney was investigated. Lp-X was isolated from plasma ofpatients with familial LCAT deficiency by sequential ultracentrifugation andgel filtration column chromatography. Rat kidneys were perfused for 1-2 hwith Krebs-Henseleit buffer containing 20 µM [1-14C]acetate or 20µM [Me-3H]choline. In the presence of Lp-X, no significant differencein the incorporation of radioactivity into triglycerides, cholesterol,phosphocholine, CDP-choline and sphingomyelin was observed. However,incorporation of radioactivity into cholesteryl esters andphosphatidylcholine was significantly elevated in Lp-X perfused kidneys. Thecontents of cholesterol, cholesteryl esters and phosphatidylcholine werealso significantly increased in Lp-X perfused kidneys. The increase in lipidcontent in the Lp-X perfused kidney is attributed to the direct depositionof Lp-X lipids into the organ. The increase in the labelling of cholesterylesters was attributed to the increase of available substrate (cholesterol)for the acyl-CoA:cholesterol acyltransferase (ACAT) reaction. The increasein phosphatidylcholine labelling was caused by a reduced turnover of thenewly synthesized labelled phosphatidylcholine during Lp-X perfusion.     

Effect of thiochrome capronate on lipid metabolism in rats

Thiochrome caproate modified by the oxyethyl radical of the thiochrome derivative was studied for its effect on different indices of lipid metabolism in the liver and blood of albino rats. It was shown that when animals were fed on a standard laboratory diet, thiochrome caproate changed the amount of total and free fatty acids in the studied tissues and the fatty acid composition in the liver to a greater extent than thiochrome and hydroxythiamine.     

Effect of diosgenin on lipid metabolism in rats.

The purpose of this study was to determine whether diosgenin suppresses cholesterol absorption in rats, and to examine relevant changes in cholesterol and bile acid metabolism. Diosgenin fed with the diet for 1 week inhibited cholesterol absorption as determined by the serum isotope ratio technique, as well as by measuring in the feces the amount of unabsorbed radioactivity from orally administered [3H]cholesterol. In addition, diosgenin suppressed the serum and liver uptake of radioactivity from co-administered [3H]cholesterol as well as the accumulation of liver cholesterol in the cholesterol-fed rat; diosgenin was substantially more active than cholestyramine or beta-sitosterol. In vitro, diosgenin had no effect on the activity of rat pancreatic esterase. Diosgenin decreased the elevated cholesterol in serum LDL and elevated cholesterol in the HDL fraction of cholesterol-fed rats; diosgenin had no effect on serum cholesterol in normocholesterolemic rats. In contrast to cholestyramine, diosgenin markedly increased neutral sterol excretion without altering bile acid excretion; in vitro, diosgenin had no effect on bile acid binding. Diosgenin treatment increased hepatic and intestinal cholesterol synthesis as well as the activity of hepatic HMG CoA reductase. This was accompanied by increased biliary concentration of cholesterol, but not of bile acids. Diosgenin had no effect on cholesterol synthesis when added to normal rat liver homogenates. It was concluded that diosgenin interferes with the absorption of cholesterol of both exogenous and endogenous origin; such interference is accompanied by derepressed, i.e., increased, rates of hepatic and intestinal cholesterol synthesis. The increased unabsorbed cholesterol together with enhanced secretion of cholesterol into bile resulted in increased excretion of neutral sterols without affecting the biliary and fecal excretion of bile acids.