title: Induction of CYP2E1 in non-alcoholic fatty liver diseases.
abstract: Mounting evidence supports a contribution of endogenous alcohol metabolism in the pathogenesis of non-alcoholic steatohepatitis (NASH). However, it is not known whether the expression of alcohol metabolism genes is altered in the livers of simple steatosis. There is also a current debate on whether fatty acids induce CYP2E1 in fatty livers. In this study, expression of alcohol metabolizing genes in the liver biopsies of simple steatosis patients was examined by quantitative real-time PCR (qRT-PCR), in comparison to biopsies of NASH livers and normal controls. Induction of alcohol metabolizing genes was also examined in cultured HepG2 cells treated with ethanol or oleic acid, by qRT-PCR and Western blots. We found that the mRNA expression of alcohol metabolizing genes including ADH1C, ADH4, ADH6, catalase and CYP2E1 was elevated in the livers of simple steatosis, to similar levels found in NASH livers. In cultured HepG2 cells, ethanol induced the expression of CYP2E1 mRNA and protein, but not ADH4 or ADH6; oleic acid did not induce any of these genes. These results suggest that elevated alcohol metabolism may contribute to the pathogenesis of NAFLD at the stage of simple steatosis as well as more severe stages. Our in vitro data support that CYP2E1 is induced by endogenous alcohol but not by fatty acids.
authors.affiliation: Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, Department of Pediatrics, SUNY at Buffalo, United States.
authors.forename: Ghanim
authors.initials: G
authors.lastname: Aljomah
authors.affiliation: Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, Department of Pediatrics, SUNY at Buffalo, United States. Electronic address: sbaker@upa.chob.edu.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Baker
authors.affiliation: Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, Department of Pediatrics, SUNY at Buffalo, United States.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pathology, SUNY at Buffalo, Women and Children's Hospital of Buffalo, Buffalo, NY 14214, United States.
authors.forename: Rafal
authors.initials: R
authors.lastname: Kozielski
authors.affiliation: Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, Department of Pediatrics, SUNY at Buffalo, United States.
authors.forename: Janet
authors.initials: J
authors.lastname: Oluwole
authors.affiliation: Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, Department of Pediatrics, SUNY at Buffalo, United States.
authors.forename: Benita
authors.initials: B
authors.lastname: Lupu
authors.affiliation: Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, Department of Pediatrics, SUNY at Buffalo, United States.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Baker
authors.affiliation: Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, Department of Pediatrics, SUNY at Buffalo, United States. Electronic address: lixinzhu@buffalo.edu.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000201:enzymology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1
keywords: CYP2E1; NAFLD; NASH; Simple steatosis