The relation between cholesterol absorption and cholesterol synthesis in the baboon.

Abstract

To determine the relation between cholesterol absorption, total endogenous cholesterol synthesis, and hepatic cholesterol synthesis in a primate, cholesterol synthesis has been studied in biopsies of liver and ileum from normal baboons fed varying amounts of cholesterol and in biopsies of liver from baboons that had been subjected to ileal diversion. In addition, total cholesterol production rates, cholesterol absorption, and total endogenous cholesterol synthesis have been measured in these animals by a double isotope technique in which the animals were given a single injection of cholesterol-4-(14)C and fed constant amounts of cholesterol-1,2-(3)H for 4 months. From these studies, it has been concluded that on a low cholesterol intake cholesterol synthesis in the liver accounts for about three-fourths of total endogenous cholesterol production. The feeding of cholesterol produces complete inhibition of hepatic synthesis in the normal animal only when absorption approximates the amount synthesized by the liver when no cholesterol is fed, e.g., 400-500 mg/day. Finally, the intestine, which does not possess complete negative feedback control of cholesterol synthesis when cholesterol is fed, may be a significant site of nonhepatic cholesterol synthesis in these animals. In studies of four baboons subjected to ileal diversion, it was concluded that the regulation of cholesterol synthesis is distinctly different when the enterohepatic circulation is interrupted. These animals did not exhibit negative feedback of hepatic cholesterol synthesis when cholesterol was fed, despite the fact that cholesterol absorption approximated that of normal animals fed similar diets. The inference has been drawn that bile acids may be involved directly or indirectly in the regulation of hepatic cholesterol synthesis in this species or that the ileum itself may modulate the hepatic negative feedback.