CHOLESTEROL SECRETION FROM HEPATOCYTES INDUCED BY TRIACYLGLYCEROL ANDAPOLIPOPROTEIN-E

The mechanism for the increase in plasma cholesterol levels in cholest erol-fed rats following chylomicron transport was investigated in inta ct animals, in isolated perfused Liver, and in hepatocytes in monolaye r cultures. Intravenous administration of egg phosphatidylcholine in a mounts greater than those required to cause a plasma cholesterol respo nse when given as chylomicrons was without effect. This makes it unlik ely that increased plasma cholesterol levels resulted from the recruit ment of tissue cholesterol by the plasma chylomicron phospholipids tha t persisted in the plasma after triacylglycerol clearance. The hepatic origin of the increased plasma cholesterol levels was directly confir med by two hepatic perfusion experiments. When cholesterol-fed rats re ceived intravenous chylomicrons prior to isolated hepatic perfusion, m ore cholesterol was secreted by the liver than when the rats were inje cted intravenously with buffer. Perfusion of apolipoprotein E (ape E)- rich triacylglycerol emulsions through the livers also enhanced choles terol secretion. The increase in hepatocyte cholesterol secretion seen with cholesterol-fed rats was also noted in monolayer cultures follow ing incubation with apo E rich-triacylglycerol emulsions. The apolipop rotein or the emulsion alone, or apo E-rich phosphatidylcholine liposo mes, had no effect. The data confirm previous indirect observations th at the liver is the source of cholesterol that appears in plasma follo wing transport of chylomicrons or following a lipid-rich meal in chole sterol-fed rats. The data also re-emphasize the importance of providin g apo E with triacylglycerol emulsions to initiate secretion of lower density lipoproteins by the liver.