title: Ethanol stimulates bile acid formation in primary human hepatocytes.
abstract: The conversion of cholesterol to bile acids is a key pathway for elimination of cholesterol from the body, thereby reducing the risk of arteriosclerosis. Moderate consumption of ethanol has been shown to have preventive effects on cardiovascular disease and decrease the risk of gallstone formation. In the present study primary human hepatocytes were used to investigate if ethanol affected bile acid synthesis. Hepatocytes were prepared from donor liver (n=11) and treated with ethanol, 7.7 or 50 mM, for 24 h. mRNA levels for enzymes in bile acid synthesis pathways were studied and bile acid synthesis was analyzed. Treatment with 7.7 mM ethanol increased cholic acid synthesis by 20% and treatment with 50 mM ethanol up-regulated cholic acid formation by 60%. The synthesis of cholic acid increased more than that of chenodeoxycholic acid, indicating that the classical pathway for bile acid synthesis was up-regulated. Increased bile acid levels in the cells treated with ethanol were seen after approximately 20 h. mRNA expression of CYP7A1, CYP27A1, and CYP8B1 in the hepatocytes was not affected by alcohol exposure.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, S-14186 Stockholm, Sweden. lisa-mari.nilsson@ki.se
authors.forename: Lisa-Mari
authors.initials: LM
authors.lastname: Nilsson
authors.forename: Jan
authors.initials: J
authors.lastname: Sjövall
authors.forename: Stephen
authors.initials: S
authors.lastname: Strom
authors.forename: Karl
authors.initials: K
authors.lastname: Bodin
authors.forename: Greg
authors.initials: G
authors.lastname: Nowak
authors.forename: Curt
authors.initials: C
authors.lastname: Einarsson
authors.forename: Ewa
authors.initials: E
authors.lastname: Ellis
mesh_terms: D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001647:Bile Acids and Salts; D000431:Ethanol