title: Systematic transcriptome analysis reveals elevated expression of alcohol-metabolizing genes in NAFLD livers.
abstract: Obese animals and non-alcoholic fatty liver disease (NAFLD) patients exhibit elevated blood alcohol, suggesting potential contributions of alcohol metabolism to the development of NAFLD. Liver gene expression in patients with biopsy-proven mild (N = 40) and severe (N = 32) NAFLD were compared to that in healthy liver donors (N = 7) and alcoholic hepatitis (AH; N = 15) using microarrays. Principal components analyses (PCA) revealed similar gene expression patterns between mild and severe NAFLD which clustered with those of AH but were distinct from those of healthy livers. Differential gene expression between NAFLD and healthy livers was consistent with established NAFLD-associated genes and NAFLD pathophysiology. Alcohol-metabolizing enzymes including ADH, ALDH, CYP2E1, and CAT were up-regulated in NAFLD livers. The expression level of alcohol-metabolizing genes in severe NAFLD was similar to that in AH. The NAFLD gene expression profiles provide new directions for future investigations to identify disease markers and targets for prevention and treatment, as well as to foster our understanding of NAFLD pathogenesis and pathophysiology. Particularly, increased expression of alcohol-metabolizing genes in NAFLD livers supports a role for endogenous alcohol metabolism in NAFLD pathology and provides further support for gut microbiome therapy in NAFLD management. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley © Sons, Ltd.
authors.affiliation: Department of Bioinformatics, Tongji University, Shanghai, China.
authors.forename: Ruixin
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Digestive Diseases and Nutrition Center, Department of Pediatrics, The State University of New York at Buffalo, Buffalo, New York, USA.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Baker
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Duke University, Durham, North Carolina, USA.|Division of Gastroenterology and Hepatology, Department of Medicine, Durham Veterans Affairs Medical Center, Durham, North Carolina, USA.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Moylan
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Duke University, Durham, North Carolina, USA.
authors.forename: Manal F
authors.initials: MF
authors.lastname: Abdelmalek
authors.affiliation: Department of Pathology, Duke University, Durham, North Carolina, USA.
authors.forename: Cynthia D
authors.initials: CD
authors.lastname: Guy
authors.affiliation: Liver Transplantation Center, Brotzu Hospital, 09134, Cagliari, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Zamboni
authors.affiliation: Department of Bioinformatics, Tongji University, Shanghai, China.
authors.forename: Dingfeng
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Bioinformatics, Tongji University, Shanghai, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Lin
authors.affiliation: Digestive Diseases and Nutrition Center, Department of Pediatrics, The State University of New York at Buffalo, Buffalo, New York, USA.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Liu
authors.affiliation: Digestive Diseases and Nutrition Center, Department of Pediatrics, The State University of New York at Buffalo, Buffalo, New York, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Baker
authors.affiliation: Department of Pathology, University of Southern California, Los Angeles, California, USA.
authors.forename: Sugantha
authors.initials: S
authors.lastname: Govindarajan
authors.affiliation: Department of Bioinformatics, Tongji University, Shanghai, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Farci
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Duke University, Durham, North Carolina, USA.
authors.forename: Anna Mae
authors.initials: AM
authors.lastname: Diehl
authors.affiliation: Digestive Diseases and Nutrition Center, Department of Pediatrics, The State University of New York at Buffalo, Buffalo, New York, USA.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000438:Alcohols / Q000378:metabolism*; D001706:Biopsy; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D000438:Alcohols
keywords: ADH; ALDH; CYP2E1; non-alcoholic