Influence of bezafibrate on hepatic cholesterol metabolism in gallstone patients: reduced activity of cholesterol 7 alpha-hydroxylase.
Bezafibrate is a hypolipidemic fibric acid derivative known to induce cholesterol supersaturation of bile. To characterize its effects on hepatic cholesterol metabolism, 31 normolipidemic, normal-weight patients with gallstones undergoing cholecystectomy were studied. Eleven patients (5 men) were randomized to treatment with bezafibrate, 200 mg three times daily for 4 weeks before operation; the remaining 20 patients (5 men) served as nontreatment controls. At operation, a liver biopsy specimen was obtained under standardized conditions and several important parameters of cholesterol metabolism were assayed. Bezafibrate treatment lowered total plasma cholesterol and triglycerides 30% and 37%, respectively. The hepatic cholesterol 7 alpha-hydroxylase activity was reduced by approximately 60% in the bezafibrate treated patients compared with the controls, whereas the acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity was similar in the two groups. The total 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity was increased twofold in the treated patients, whereas the active enzyme remained about the same as in the controls. The low-density lipoprotein (LDL) receptor binding activity was unaffected by the treatment. Bezafibrate treatment significantly reduces cholesterol 7 alpha-hydroxylase activity, and it is suggested that this may play an important role for the development of supersaturated bile during such therapy.
Ståhlberg
D
D
Department of Medicine, Karolinska Institutet, Huddinge University Hospital, Sweden.
Reihnér
E
E
Rudling
M
M
Berglund
L
L
Einarsson
K
K
Angelin
B
B
D000328:Adult; D000368:Aged; D001629:Bezafibrate / Q000494:pharmacology*; D002769:Cholelithiasis / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism*; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D002785:Sterol O-Acyltransferase / Q000378:metabolism
D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase; D002785:Sterol O-Acyltransferase; D001629:Bezafibrate