title: Insulin resistance alters hepatic ethanol metabolism: studies in mice and children with non-alcoholic fatty liver disease.
abstract: Increased fasting blood ethanol levels, suggested to stem from an increased endogenous ethanol synthesis in the GI tract, are discussed to be critical in the development of non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to further delineate the mechanisms involved in the elevated blood ethanol levels found in patients with NAFLD.
  
  
  
  In 20 nutritionally and metabolically screened children displaying early signs of NAFLD and 29 controls (aged 5-8 years), ethanol plasma levels were assessed. Ethanol levels along the GI tract, in vena cava and portal vein, intestinal and faecal microbiota, and activity of alcohol dehydrogenase (ADH) and cytochrome P450 2E1 (CYP2E1) were measured in wild-type, ob/ob and anti-TNFα antibody (aT) treated ob/ob mice.
  
  
  
  Despite not differing in dietary pattern or prevalence of intestinal overgrowth, fasting ethanol levels being positively associated with measures of insulin resistance were significantly higher in children with NAFLD than in controls. Ethanol levels were similar in portal vein and chyme obtained from different parts of the GI tract between groups while ethanol levels in vena cava plasma were significantly higher in ob/ob mice. ADH activity was significantly lower in liver tissue obtained from ob/ob mice in comparison to wild-type controls and ob/ob mice treated with aT.
  
  
  
  Taken together, our data of animal experiments suggest that increased blood ethanol levels in patients with NAFLD may result from insulin-dependent impairments of ADH activity in liver tissue rather than from an increased endogenous ethanol synthesis.
  
  
  
  NCT01306396.
authors.affiliation: Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Anna Janina
authors.initials: AJ
authors.lastname: Engstler
authors.affiliation: Institute of Animal Nutrition, University of Hohenheim, Stuttgart, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Aumiller
authors.affiliation: Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Degen
authors.affiliation: Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Dürr
authors.affiliation: Institute of Animal Nutrition, University of Hohenheim, Stuttgart, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Weiss
authors.affiliation: Department of Nutritional Medicine (180a), University of Hohenheim, Stuttgart, Germany.
authors.forename: Ina Barbara
authors.initials: IB
authors.lastname: Maier
authors.affiliation: I. Department of Medicine, University Medical Center Mainz, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Jörn Markus
authors.identifier: 0000-0002-4224-4703
authors.initials: JM
authors.lastname: Schattenberg
authors.affiliation: Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Cheng Jun
authors.initials: CJ
authors.lastname: Jin
authors.affiliation: Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Sellmann
authors.affiliation: Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Bergheim
mesh_terms: D000426:Alcohol Dehydrogenase / Q000097:blood / Q000378:metabolism; D000818:Animals; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D019392:Cytochrome P-450 CYP2E1 / Q000097:blood; D000431:Ethanol / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000175:diagnosis / Q000378:metabolism; D009747:Nutritional Physiological Phenomena; D013223:Statistics as Topic
chemical_list: D000431:Ethanol; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1
keywords: BACTERIAL OVERGROWTH; ETHANOL; FATTY LIVER; TNF-ALPHA