Effects of dietary 27-hydroxycholesterol on cholesterol metabolism and bile acid biosynthesis in the hamster.
(Can J Physiol and Pharmacol 2003; 81 : 854-863.) Maâmar Souidi*, Sandrine Dubrac, Michel Parquet, Fabien Milliat, Jacqueline Férézou, Colette Sérougne, Carole Loison, Michel Riottot, Nawel Boudem, Thierry Bécue, Claude Lutton
27-hydroxycholesterol (27OH-Chol) is an important endogenous oxysterol, resulting from the action of sterol 27-hydroxylase (CYP27A1) on cholesterol in the liver as well as in numerous extrahepatic tissues. It could have modulating properties of the 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 one week. Intestinal scavenger class B, type 1 protein level was decreased (-65%) but hepatic expression was increased (+34%). Liver 3b-hydroxy-3b-methyl glutaryl coenzyme A reductase (-58%), cholesterol 7a-hydroxylase (-54%), oxysterol 7a-hydroxylase (-44%) and sterol 12a-hydroxylase (- 70%) activities were all decreased. Bile acid composition was changed (chenodeoxycholic / cholic ratio x 4). This study demonstrates that dietary 27OH-Chol modulates major enzymes of cholesterol metabolism and alters the biliary bile acid profile to more hydrophobic, at least, at this level of intake. Its effects on SR-B1 protein level are organ-dependent. The properties of 27OH-Chol or its metabolites on the cholesterol metabolism probably result from the activation of specific transcription factors.