Sterol balance studies in the rat. Effects of dietary cholesterol and beta-sitosterol on sterol balance and rate-limiting enzymes of sterol metabolism.
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.
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D002791:Cholesterol, Dietary; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D005243:Feces / Q000032:analysis; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007783:Lactones; D008798:Mevalonic Acid / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D012855:Sitosterols / Q000494:pharmacology*; D013261:Sterols / Q000378:metabolism*; D013997:Time Factors
D002791:Cholesterol, Dietary; D007783:Lactones; D012855:Sitosterols; D013261:Sterols; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase; D008798:Mevalonic Acid