Relationship of Alcoholic Hyperlipidemia to the Feed‐Back Regulation of Hepatic Cholesterol Synthesis by Chylomicron Remnants

Abstract

Pairfeeding of ethanol liquid diet for 6 weeks to male Wistar rats resulted in defective extrahepatic as well as hepatic catabolism of rat lymph chylomicrons. Based upon the exponential decay curves of the chylomicrons in the blood compartment it was concluded that chronic ethanol feeding caused 30 and 67% decreases in the rate of degradation of the triacylglycerol and cholesterol moieties, respectively. As a consequence, abnormal chylomicron remnants accumulated in chronic ethanol-fed but not in control animals. These abnormal remnants were not as efficient as the normal remnants in causing the feedback inhibition of cholesterol synthesis in hepatocytes from normal meal-fed rats. Furthermore, the hepatocytes from chronic ethanol-fed animals exhibited defective feedback regulation of cholesterol synthesis by normal chylomicron remnants. The net result of all these abnormalities caused by chronic ethanol feeding would be the delayed clearance of triacylglycerol-rich lipoproteins from the blood compartment and enhanced synthesis and secretion of the triacylglycerol-rich lipoproteins by the liver.