Effects of dietary 27-hydroxycholesterol on cholesterol metabolism and bile acid biosynthesis in the hamster

Abstract

27-hydroxycholesterol (27OH-Chol) is an important endogenous oxysterol resulting from the action of sterol 27-hydroxylase (CYP27A1) on cholesterol in the liver and numerous extrahepatic tissues. It may act as a modulator of cholesterol and bile acid metabolism. The effects of 27OH-Chol on the main enzymes and receptors of cholesterol metabolism were investigated by feeding male hamsters a diet supplemented with 27OH-Chol (0.1% w/w) for 1 week. Intestinal scavenger class B, type I (SR-BI) protein level was decreased (–65%), but hepatic expression was increased (+34%). Liver 3β-hydroxy-3β-methyl glutaryl coenzyme A reductase (–58%), cholesterol 7α-hydroxylase (–54%), oxysterol 7α-hydroxylase (–44%), and sterol 12α-hydroxylase (–70%) activities were all decreased. Bile acid composition was changed (fourfold increase in the chenodeoxycholic/cholic acid ratio). This study demonstrates that dietary 27OH-Chol modulates major enzymes of cholesterol metabolism and alters the biliary bile acid profile, making it more hydrophobic, at least at this level of intake. Its effects on SR-BI protein levels are organ dependent. The properties of 27OH-Chol or its metabolites on cholesterol metabolism probably result from the activation of specific transcription factors. Key words: cholesterol 7α-hydroxylase (CYP7A1), sterol 12α-hydroxylase (CYP8B1), sterol 27-hydroxylase (CYP27A1), 3β-hydroxy-3β-methyl glutaryl coenzyme A reductase (HMGCoAR), scavenger receptor class B type I (SR-BI).