Effect of cholesterol feeding and biliary obstruction on hepatic cholesterol biosynthesis in the rat

Abstract

1. 1. It has been suggested that the amount of cholesterol reaching the liver from the intestine determines the suppression of cholesterol biosynthesis which occurs with cholesterol feeding and the rise in synthesis which occurs with bile duct ligation. We hypothesized that microsomal cholesteryl ester might be the inhibitor. 2. 2. Cholesterol feeding suppressed cholesterol biosynthesis in rat liver slices; although there was little change in hepatic free cholesterol levels, hepatic and microsomal cholesteryl ester levels rose markedly. Following the cessation of cholesterol feeding synthesis returned to normal with a corresponding fall in microsomal cholesteryl ester levels. These observations would agree with our hypothesis. 3. 3. Biliary obstruction increased hepatic cholesterol biosynthesis to levels greater than those found at the peak of normal diurnal variation, but microsomal cholesteryl ester levels did not fall. 4. 4. Cholesterol feeding prior to obstruction inhibited the rise in cholesterol biosynthesis as did the administration of dl-ethionine or cycloheximide. These results suggest that the microsomal cholesteryl ester level may be an inhibitor of cholesterol biosynthesis but other factors including protein synthesis are involved in the elevation of synthesis following bile duct ligation.