role of alcohol metabolism in non-alcoholic steatohepatitis在非酒精性脂肪肝酒精代谢的作用.pdfVIP

Role of Alcohol Metabolism in Non-Alcoholic Steatohepatitis 1 1 1 2,3 1 Susan S. Baker , Robert D. Baker , Wensheng Liu , Norma J. Nowak , Lixin Zhu * 1 Digestive Diseases and Nutrition Center, Department of Pediatrics, The State University of New York, Buffalo, New York, United States of America, 2 Department of Biochemistry and the New York State Center of Excellence in Bioinformatics and Life Sciences, The State University of New York at Buffalo, Buffalo, New York, United States of America, 3 Microarray and Genomics Facility, Roswell Park Cancer Institute, Buffalo, New York, United States of America Abstract Background: Non-alcoholic steatohepatitis (NASH) is a serious form of non-alcoholic fatty liver disease (NAFLD), associated with obesity and insulin resistance. Previous studies suggested that intestinal bacteria produced more alcohol in obese mice than lean animals. Methodology/Principal Findings: To investigate whether alcohol is involved in the pathogenesis of NASH, the expression of inflammation, fibrosis and alcohol metabolism related genes in the liver tissues of NASH patients and normal controls (NCs) were examined by microarray (NASH, n = 7; NC, n = 4) and quantitative real-time PCR (NASH, n = 6; NC, n = 6). Genes related to liver inflammation and fibrosis were found to be elevated in NASH livers compared to normal livers. The most striking finding is the increased gene transcription of alcohol dehydrogenase (ADH) genes, genes for catalase and cytochrome P450 2E1, and aldehyde dehydrogenase genes. Immunoblot analysis confirmed the increased expression of ADH1 and ADH4 in NASH livers (NASH, n = 9; NC, n = 4). Conclusions/Significance: The augmented activity of all