Faculty Bibliography

The keto acid, gamma-oxo-gamma-(8-fluoranthene)butyric acid (Zanchol) markedly alters sterol metabolism in rats. It stimulates cholesterol and bile acid synthesis and decreases cholesterol absorption

Sterol metabolism studies using a combination of isotopic and chromatographic procedures were carried out in rats fed either a low-cholesterol stock diet or a stock diet containing 0.1% cholesterol. The primary bile acids, sodium taurochenodeoxycholate and sodium taurocholate, were added to the stock diets at a level of 0.5%, as required. Feeding sodium taurochenodeoxycholate and sodium taurocholate led to a decrease in acidic steroid synthesis, cholesterol turnover, and cholesterol balance, compared to controls. Sodium taurochenodeoxycholate feeding did not influence cholesterol absorption, but rats fed sodium taurocholate showed a twofold increase in cholesterol absorption as well as an accumulation of cholesterol in the liver. Rats receiving diets containing sodium taurochenodeoxycholate or sodium taurocholate plus cholesterol (0.1%) showed decreased acidic steroid synthesis, cholesterol turnover, and cholesterol balance, compared to the corresponding controls (Group 2, high cholesterol diet). Significantly larger amounts of cholesterol were absorbed in the taurocholate group (34.1 mg/day); these animals increased their concentrations of cholesterol in liver and plasma. The rats fed taurocholate plus 0.1% cholesterol differed from those fed taurochenodeoxycholate plus 0.1% cholesterol in the following respects: a) increased cholesterol absorption (35%), and b) accumulation of cholesterol in liver and plasma

Sterol balance measurements using isotopic and chromatographic techniques were carried out in rats fed diets containing beta-sitosterol (0.8%) and cholesterol (1.2%). The activities of the rate-limiting enzymes of cholesterol synthesis (beta-hydroxy-beta-methylglutaryl-CoA reductase, EC 1.1.1.34) and bile acid synthesis (cholesterol 7 alpha-hydroxylase) were determined in the same animals. Cholesterol feeding increased cholesterol absorption from 1.2 to 70 mg/day. The increased absorption was compensated for by inhibition of hepatic cholesterol synthesis, enhanced conversion of cholesterol to bile acids (from 13.7 to 27.3 mg/day) and a slight increase in the excretion of endogenous neutral steroids (from 7.7 to 11.2 mg/day). Despite the adaptation there was accumulation of cholesterol in the liver (from 2.2 to 9.2 mg/g). Beta-Sitosterol feeding inhibited cholesterol absorption (calculated absorption was zero). In these rats there was enhanced cholesterol synthesis (from 20.0 to 28.8 mg/day, but no change in the rates of bile acid formation. Measurements of the activities of the rate-limiting enzymes showed fair correlation with cholesterol-bile acid balance. In cholesterol fed animals, beta-hydroxy-beta-methylglutaryl-CoA reductase was inhibited 80% and cholesterol 7 alpha-hydroxylase was enhanced 61%. In beta-sitosterol-fed animals, the reductase was increased 2-fold and cholesterol 7 alpha-hydroxylase was not significantly different from controls