Regulation of Serum Cholesterol Level by the Liver:Relationship with Development of Hypercholesterolemia, Aging and Genetic Factor

概要

論文の詳細を見る
The effects of genetic factor and aging on development of hypercholesterolemia were studied using the rats with different responsiveness for a high cholesterol diet and those with different ages. Labeled cholesterol in various serum lipoprotein fractions was actively taken up by isolated hepatocytes in vitro when incubated at 37.5°C. Although the uptake ratio from HDL was lower than those from other lipoprotein fractions, the net amount of removed serum cholesterol was larger than those from VLDL or chylomicrons, because cholesterol concentration in HDL was markedly higher than that in VLDL or chylomicrons. Therefore, serum HDL-protein seems to play a significant role for hepatic uptake of cholesterol in vivo as well as LDL-protein. The isolated hepatocytes from the hyporesponded rats to cholesterol administration removed serum cholesterol much more than those from the hyperresponded rats in vitro. It is proposed that the reduced uptake of serum cholesterol by those cells may cause a decrease in feed back control for cholesterol synthesis and consequently an increase in synthetic activity. However, in the present experiment, the increase of cholesterol synthesis was not observed in the liver from such hyperresponded rats. The half lives of serum cholesterol were shown to delay in these hyperresponders, suggesting the decrease rate of the clearance of cholesterol from peripheral circulation. Therefore, it is suggested that the decreased uptake of serum cholesterol does not always induce the increase of hepatic cholesterol synthesis due to the impairment of feed back control, but the reduced clearance of serum cholesterol from peripheral circulation. Elevation of the serum cholesterol concentration in the hyperresponder by aging was larger than that in the hyporesponder. It means that a genetic defect concerning cholesterol metabolism was emphasized by the retardation of cholesterol metabolism by aging. The stimulation of hepatic cholesterol synthesis caused an enhancement in enzyme activities of cholesterol metabolism, for example cholesterol 7α-hydroxylase and enzymes for bile acids especially cholic acid synthesis. Cholic acid and its secondary bile acid, deoxycholic acid, are well reabsorbed from the intestine and result in an enlargement of pool size of bile acids. By contrast, the reabsorption of lithocholic acid which is formed from chenodeoxycholic acid by the intestinal micro-organism is lower than those of other bile acids and consequently easily excreted into feces. Such an increase of the pool size inhibits the enzyme activities for cholesterol synthesis as well as those for cholesterol catabolism. Thus, cholesterol synthesis and catabolism are well correlated and enhanced cholesterol synthesis is readily restored by the increased of bile acid formation to keep the homeostasis of serum cholesterol level. Although the hepatic uptake of serum cholesterol was reduced in old rats, synthetic activity of hepatic cholesterol was not enhanced but decreased markedly. Hepatic cholesterol synthesis from acetate, mevalonic acid or squalene in microsomal fractions was decreased in old rats. Well washed microsomes showed no synthetic activity of cholesterol in vitro without the addition of hepatic cytosol fraction, which contains sterol carrier proteins. When hepatic cytosol from the old was added to the microsomes from the young animals instead of young cytosol, the cholesterol synthesis from squalene as well as mevalonic acid in the young microsomes were decreased markedly. Thus, the impairment of the function of sterol carrier protein is suggested in aging in which the activities of microsomal enzymes are decreased.
Japan Society of Clinical Chemistryの論文

Regulation of Serum Cholesterol Level by the Liver:Relationship with Development of Hypercholesterolemia, Aging and Genetic Factor

スポンサーリンク

概要

著者

関連論文

スポンサーリンク