Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in mice

• Published in: Hepatology (Baltimore, Md.) Vol. 42; no. 3; pp. 568 - 577
• Main Authors: MIN YOU, CONSIDINE, Robert V, LEONE, Teresa C, KELLY, Daniel P, CRABB, David W
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley 01-09-2005
• Subjects: 3-Hydroxybutyric Acid - blood; Acetyl-CoA Carboxylase - metabolism; Adiponectin; Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Cholesterol - metabolism; Dietary Fats - therapeutic use; Disease Models, Animal; Diseases of the digestive system; Ethanol - toxicity; Fatty Liver - prevention & control; Fatty Liver, Alcoholic - prevention & control; Gastroenterology. Liver. Pancreas. Abdomen; Intercellular Signaling Peptides and Proteins - blood; Intercellular Signaling Peptides and Proteins - genetics; Liver - drug effects; Liver - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Mice; Mice, Inbred C57BL; Other diseases. Semiology; Phosphorylation; PPAR alpha - genetics; Promoter Regions, Genetic; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); RNA, Messenger - genetics; Toxicology; Triglycerides - metabolism; AMP; Alcoholism; Rodentia; Hepatic disease; Adiponectin; Prevention; Vertebrata; Chronic; Mammalia; Fatty liver; Diet therapy; Diet; Mouse; Animal; Fat; Digestive diseases
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.20821

The protective effect of dietary saturated fatty acids against the development of alcoholic liver disease has long been known, but the underlying mechanism is not completely understood. We examined the involvement of the adipocyte hormone adiponectin. Circulating adiponectin levels were significantly elevated by chronic ethanol administration to mice consuming a diet high in saturated fat. The increase in circulating adiponectin was associated with the activation a set of hepatic signaling pathways mediated through AMP-activated protein kinase, PPAR-alpha, and PPAR-gamma coactivator alpha, which in turn led to markedly increased rates of fatty acid oxidation, prevention of hepatic steatosis, and alleviation of liver enzyme changes. Furthermore, treatment of rat 3T3-L1 adipocytes with saturated fatty acids (palmitic or stearic acids) in the presence of ethanol increased secretion of adiponectin and enhanced activity of a mouse adiponectin promoter. In conclusion, the protective action of saturated fat against the development of alcoholic fatty liver in mice is partially mediated through induction of adiponectin. The present findings suggest a novel paradigm for dietary fatty acids in the pathogenesis of alcoholic liver disease and provide a promising therapeutic strategy-nutritional modulation of adiponectin-in treating human alcoholic fatty liver disease.