Sterol metabolism in the rat: Effect of cholesterol and cholesterol-α-epoxide on sterol metabolism in rats fed liquid diets

Abstract

Certain oxygenated derivatives of cholesterol have dramatic effects on cholesterol synthesis. The present study compared the effects of cholesterol and an oxygenated metabolite, cholesterol-α-epoxide, on sterol metabolism in rats. Sterol balance measurements using isotopic and chromatographic techniques were carried out in rats fed liquid control diets, control diets + cholesterol (1 mg/ml), and control diets + cholesterol-α-epoxide (1 mg/ml). Sterol metabolism was affected by both cholesterol and cholesterol-α-epoxide. Cholesterol feeding decreased cholesterol synthesis (−9.57 ± 7.23 mg/day), increased endogenous bile acid synthesis (7.71 ± 1.18 mg/day), and increased cholesterol turnover (7.78 ± 2.33 mg/day) compared to controls. Cholesterol-α-epoxide had no effect on cholesterol synthesis, endogenous bile acid synthesis and cholesterol turnover compared to controls. However, animals fed cholesterol-α-epoxide had large increases in total acidic steroid output (determined by chromatographic analysis, 12.23 ± 4.05 mg/day). This finding suggests that cholesterol-α-epoxide is absorbed and converted to bile acids. Apparently, the epoxide enters the bile acid biosynthetic pathway distal to the rate-limiting step of 7α-hydroxylation. As a result, large amounts of bile acids are formed from the epoxide without affecting endogenous cholesterol or bile acid synthesis. This was confirmed in a separate experiment by feeding [4- 14C]cholesterol-α-epoxide and recovering labeled bile acids (hyodeoxycholic acid and lithocholic acid) as well as the starting radioactively labeled epoxide in the feces.