Decreased Hepatic Uptake and Processing of High Density Lipoprotein Unesterified Cholesterol and Cholesteryl Ester with Age in the Rat1

Abstract

As part of a study of the effects of aging on lipoprotein metabolism, the uptake and processing in vivo of cholesterol from high density lipoprotein (HDL) was compared in young (3 months of age) and mature (10-12 months of age) rats by studying the fate of HDL [3H] unesterified cholesterol or [3H] cholesteryl ester after intravenous administration. Radioactivity from [3H] unesterified cholesterol was cleared from the blood more slowly in older rats, and this difference was accounted for by decreased uptake by the liver. Uptake by other tissues were unaffected. In addition, a shift in the distribution of radioactivity across the plasma lipoprotein density range from the d = 1.125-1.250 g/ml (HDL3) to the d = 1.050-1.085 g/ml (HDL1) fraction was observed in the mature as compared to the young rat group. The secretion of radioactivity from [3H] unesterified cholesterol into bile was also decreased in the older animals, particularly in the first hour after injection of the label. In the case of HDL labeled with [3H] cholesteryl ester, clearance from the blood was similar in both age groups in the first 30 min after injection, but was significantly lower in older rats at later time points. After 180 min, less radioactivity was found in the VLDL density fraction in mature as compared to young rats, suggesting that hepatic secretion of VLDL cholesterol originating from HDL cholesteryl ester is less efficient in the older animals. The amount of radioactivity from HDL [3H] cholesteryl ester secreted in bile was less in the mature rat group at all time points measured.(ABSTRACT TRUNCATED AT 250 WORDS)