Effects of dietary 27-hydroxycholesterol on cholesterol metabolism and bile acid biosynthesis in the hamster.
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 3beta-hydroxy-3beta-methyl glutaryl coenzyme A reductase (-58%), cholesterol 7alpha-hydroxylase (-54%), oxysterol 7alpha-hydroxylase (-44%), and sterol 12alpha-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.
Souidi
Maâmar
M
Laboratory of Physiology and Nutrition, Bâtiment 447, Université Paris-Sud, 91405 Orsay CEDEX, France.
Dubrac
Sandrine
S
Parquet
Michel
M
Milliat
Fabien
F
Férézou
Jacqueline
J
Sérougne
Colette
C
Loison
Carole
C
Riottot
Michel
M
Boudem
Nawel
N
Bécue
Thierry
T
Lutton
Claude
C
D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004032:Diet; D006888:Hydroxycholesterols / Q000378:metabolism / Q000494:pharmacology*; D006900:Hydroxylation; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007118:Immunoassay; D007421:Intestine, Small / Q000201:enzymology / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D018110:Receptors, Lipoprotein / Q000096:biosynthesis
D001647:Bile Acids and Salts; D006888:Hydroxycholesterols; D008074:Lipoproteins; D018110:Receptors, Lipoprotein; C076996:27-hydroxycholesterol; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases