Effect of cholesterol and bile acids on the regulation of cholesterol metabolism in hamster

Abstract

Cholesterol metabolism studies were carried out in the golden Syrian hamster ( Mesocricetus auratus) fed a chow diet supplemented with cholesterol, bile acids or both for 1 month. Addition of cholesterol (0.15 or 1%) to the chow diet produced dose-related increases in plasma and liver cholesterol and lowered hepatic microsomal hydroxymethylglutaryl-CoA reductase activity by 90%. Supplementation of the stock diet with 2% cholestyramine reduced plasma cholesterol by 20% and caused a 5-fold increase in hydroxymethyl-glutaryl-CoA] reductase activity. The cholesterol diets increased the proportion of chenodeoxycholic acid in bile at the expense of cholic acid while cholestyramine had the opposite effect. The lithogenic index of bile increased significantly during the cholesterol and cholestyramine regimens, but remained well below 1.0. Addition of 0.1% bile acid to the stock diet (0.01% cholesterol) produced significant increases in plasma cholesterol in the chenodeoxycholic acid and cholic acid groups and in liver cholesterol in the cholic acid group. Hepatic hydroxymethylglutaryl-CoA reductase was significantly depressed only in the cholic acid group. The effects of ursodeoxycholic acid on plasma and liver cholesterol were not significant. The administered bile acids predominated in bile. The chenodeoxycholic acid and ursodeoxycholic acid groups showed a significant increase in biliary lithocholic acid. More lithocholic acid formed from chenodeoxycholic acid than from ursodeoxycholic acid. The lithogenic index increased in the chenodeoxycholic acid and cholic acid groups but remained below 1.0. In animals on the 0.15% cholesterol diet ursodeoxycholic acid prevented the accumulation of cholesterol in plasma and liver to a moderate extent, while chenodeoxycholic acid reduced liver cholesterol only. Hepatic hydroxymethylglutaryl-CoA reductase was very low on the 0.15% cholesterol diet and was not reduced further by dietary bile acids. Animals on the 0.15 or 1% cholesterol diets had smaller proportions of secondary bile acids (deoxycholic acid and lithocholic acid) in bile than did hamsters on the chow diet. The lithogenic index was below 1.0 in all groups, but was lowest with the ursodeoxycholic acid regimen. The dietary bile acids had relatively little effect on endogenous bile acid and neutral sterol production in hamsters on high cholesterol intakes. Cholesterol absorption averaged about 60% on the 0.15% cholesterol control diet and on the same diet with added cholic acid. Ursodeoxycholic acid and chenodeoxycholic acid reduced the absorption but the difference from the controls was significant with ursodeoxycholic acid only. Under the conditions employed, the effect of bile acids on cholesterol metabolism in the hamster depends on the cholesterol content of the diet.