Bile acid feeding and hepatic sterol metabolism: Effect of deoxycholic acid

Abstract

The effect of deoxycholic acid feeding on hepatic sterol metabolism was studied in 9 subjects with cholesterol gallstones. Fifteen milligrams per kilogram of deoxycholic acid was given daily for 1–2 wk before cholecystectomy. During the study the subjects were maintained on a standard diet containing approximately 500 mg of cholesterol daily. Parameters investigated included bile acid pool composition, HMG-CoA reductase, 7α-hydroxylase, microsomal cholesterol, biliary lipids, and plasma lipids. No relevant side effects were noted. At the end of the treatment the fed bile acid constituted nearly 90% of the bile acid pool. In the treated group hepatic HMG-CoA reductase was reduced by 45%, as compared with the control value (mean ± SD : 40.4 ± 10.3 pmol/min/mg protein vs. 72.9 ± 8.4 pmol/min/mg protein; P < 0.01); 7α-hydroxylase activity did not change, whereas microsomal cholesterol was somewhat reduced (65.2 ± 9.1 nmol/mg protein vs. 76.5 ± 12.4 nmol/mg protein of the controls; P < 0.05). Baseline saturation index of the bile was not different after treatment. Plasma cholesterol was lowered by 20% (184 ± 17 mg/dl vs. 232 ± 27 mg/dl before treatment; P < 0.03), whereas plasma triglycerides were unaffected by DCA feeding. In conclusion, deoxycholic acid administration seems to depress the hepatic synthesis of cholesterol without changing biliary lipid composition and, in addition, it lowers plasma cholesterol.