PLASMA LIPOPROTEIN METABOLISM IN PERFUSED RAT LIVERS. II. TRANSFER OF FREE AND ESTERIFIED CHOLESTEROL INTO THE PLASMA*

Abstract
The metabolism of the free and esterified cholesterol of the plasma lipoproteins was studied. Ester cholesterol, unlike free cholesterol, does not exchange between lipoprotein fraction in vitro. This property makes ester cholesterol a unique indicator of lipoprotein metabolism in vivo. Perfusion of livers of cholesterol-fed rats resulted in a marked increase in cholesterol concentration in the perfusate. This increase occurred in the very low density lipoproteins (VLD). Gas chromatographic analysis showed that most of the transferred cholesterol ester was the oleate, which predominates in the livers of the cholesterol fed rats. By the end of the perfusion, the sterol ester composition of the VLD became similar to that of the perfused liver. In normal rats, the fatty acid composition of the cholesterol esters of the VLD also resembles that in the liver. The transfer of radioactive cholesterol ester from liver to plasma was studied in perfusions in which the liver cholesterol esters were labeled by administration of mevalonic acid-2- C14. The cholesterol esters from the VLD fraction had the highest specific activity of all the lipoproteins at the end of perfusions. This fraction appears to have the most rapid turnover of both its lipid and protein constituents. These studies suggest that the cholesterol esters of the VLD are derived by direct, nonselective transfer of cholesterol esters from the liver, whereas the cholesterol esters of the higher density lipoproteins are derived from the liver cholesterol esters oy a process which is slower and selective with respect to individual esters.