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Insulin resistance alters hepatic ethanol metabolism: studies in mice and children with non-alcoholic fatty liver disease
  1. Anna Janina Engstler1,
  2. Tobias Aumiller2,
  3. Christian Degen1,
  4. Marion Dürr1,
  5. Eva Weiss2,
  6. Ina Barbara Maier3,
  7. Jörn Markus Schattenberg4,
  8. Cheng Jun Jin1,
  9. Cathrin Sellmann1,
  10. Ina Bergheim1
  1. 1Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller-University Jena, Jena, Germany
  2. 2Institute of Animal Nutrition, University of Hohenheim, Stuttgart, Germany
  3. 3Department of Nutritional Medicine (180a), University of Hohenheim, Stuttgart, Germany
  4. 4I. Department of Medicine, University Medical Center Mainz, Johannes Gutenberg University, Mainz, Germany
  1. Correspondence to Professor Ina Bergheim, Institute of Nutritional Sciences, SD Model Systems of Molecular Nutrition, Friedrich-Schiller-University Jena, Dornburgerstraße 25-29, 07743 Jena, Germany; ina.bergheim{at}uni-jena.de

Abstract

Objective 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.

Design 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.

Results 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.

Conclusions 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.

Trial registration number NCT01306396.

  • BACTERIAL OVERGROWTH
  • TNF-ALPHA
  • FATTY LIVER
  • ETHANOL

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