Cholesterol homeostasis in the rat with a portacaval anastomosis

Studies were undertaken to determine the effect of portacaval anastomosis on cholesterol homeostasis in rats fed sucrose/lard under conditions of normal body growth. Four to 6 weeks after portacaval shunt surgery, we found decreases in plasma cholesterol and triglyceride concentrations, total liver weight, and hepatic microsomal protein concentration. Measurements oof hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34) activity showed decreases in specific activity and total liver activity in portacaval shunt rats, but the enzyme diurnal rhythm remained. Decreased reductase activity in shunted rats was not due to an altered Km for D-HMG-COA, nor was an enzyme inhibitor found in the livers of the portacaval shunt animals. Sterol balance measurements in rats with shunts showed a 22% decrease in whole body cholesterol synthesis rate compared to controls. These metabolic studies, coupled with postmortem data, showed diminished bile acid synthesis, unchanged fecal neutral steroid excretion, and decreased net tissue accumulation of cholesterol during growth. The decreased whole body cholesterol synthesis rate ultimately led to a diminished total carcass cholesterol concentration in the rats with shunts.