Moderate alcohol consumption diminishes the development of non-alcoholic fatty liver disease (NAFLD) in ob/ob mice

• Published in: European journal of nutrition Vol. 55; no. 3; pp. 1153 - 1164
• Main Authors: Kanuri, Giridhar, Landmann, Marianne, Priebs, Josephine, Spruss, Astrid, Löscher, Marina, Ziegenhardt, Doreen, Röhl, Carolin, Degen, Christian, Bergheim, Ina
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2016; Springer Nature B.V
• Subjects: 3T3 Cells; Adiponectin - metabolism; Alcohol Drinking; Animals; Body Weight; Caspase 9 - metabolism; Cell Line; Chemistry; Chemistry and Materials Science; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Ethanol - administration & dosage; Fatty Acids, Nonesterified - blood; Insulin - blood; Intra-Abdominal Fat - metabolism; Lipid Metabolism; Liver - metabolism; Male; Mice; Mice, Obese; Non-alcoholic Fatty Liver Disease - prevention & control; Nutrition; Original Contribution; Plasminogen Activator Inhibitor 1 - metabolism; Signal Transduction; Sirtuin 1 - metabolism; Triglycerides - blood; Tumor Necrosis Factor-alpha - metabolism; Visceral fat; PAI-1; Ethanol; SIRT1; Adiponectin
• ISSN: 1436-6207; 1436-6215
• DOI: 10.1007/s00394-015-0929-7

Purpose Using ob / ob mice as a model of non-alcoholic fatty liver disease (NAFLD), we investigated the effect of moderate alcohol intake on the development of NAFLD and molecular mechanisms involved. Methods Ob / ob mice were fed water or ethanol solution (2.5 g/kg body weight/day) for 6 weeks, and markers of liver injury, insulin signalling and adiponectin in visceral adipose tissue were determined. Results Whereas bodyweight and the degree of liver steatosis did not differ among ob / ob mouse groups, those consuming ethanol had markedly less macrovesicular hepatic fat accumulation, inflammatory alterations and significantly lower transaminase levels. Despite similarly elevated protein levels of tumour necrosis factor α, protein concentrations of plasminogen activator inhibitor 1 were significantly lower in livers of ob / ob mice consuming ethanol in comparison with controls. The hepato-protective property of moderate alcohol ingestion in ob / ob mice was associated with an induction of the sirtuin-1/adiponectin-signalling cascade in visceral fat tissue and an activation of Akt in the liver. Similar effects of moderate alcohol exposure were also found in vitro in 3T3-L1 and AML-12 cells. Conclusion These data suggest that moderate alcohol intake may diminish the development of NAFLD through sirtuin-1/-adiponectin-dependent signalling cascades.