Effects of treatment with clofibrate, bezafibrate, and ciprofibrate on the metabolism of cholesterol in rat liver microsomes

The effects of treatment of rats with clofibrate, bezafibrate, and ciprofibrate on the hepatic metabolism of cholesterol were studied in rat liver microsomes. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase activity, regulating cholesterol biosynthesis, was unaffected by clofibrate and ciprofibrate and slightly decreased (20%) by bezafibrate. Also cholesterol 7 alpha-hydroxylase activity, governing bile acid biosynthesis, was unaffected by clofibrate and was reduced by 25-30% in the two other groups of rats. A major new finding was that all three fibric acid derivatives reduced ACAT (acyl-coenzyme A:cholesterol acyltransferase) activity, catalyzing the esterification of cholesterol, by 50-70%. The hepatic content of free and esterified cholesterol was determined in the bezafibrate-treated rats. The concentration of microsomal cholesteryl ester was about 60% lower in the treated rats compared to the controls whereas the concentration of total cholesterol was unchanged.