title: Sterol metabolism in the rat. Effect of cholesterol and cholesterol-alpha-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-alpha-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-alpha-epoxide (1 mg/ml). Sterol metabolism was affected by both cholesterol and cholesterol-alpha-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-alpha-epoxide had no effect on cholesterol synthesis, endogenous bile acid synthesis and cholesterol turnover compared to controls. However, animals fed cholesterol-alpha-epoxide had large increases in total acidic steroid output (determined by chromatographic analysis, 12.33 +/- 4.05 mg/day). This finding suggests that cholesterol-alpha-epoxide is absorbed and converted to bile acids. Apparently, the epoxide enters the bile acid biosynthetic pathway distal to the rate-limiting step of 7 alpha-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-alpha-epoxide and recovering labeled bile acids (hyodeoxycholic acid and lithyocholic acid) as well as the starting radioactively labeled epoxide in the feces.
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000494:pharmacology; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004032:Diet; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013261:Sterols / Q000378:metabolism*
chemical_list: D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D013261:Sterols; C002415:cholesterol alpha-oxide; D002784:Cholesterol