Results: Serum levels of FGF-21 were markedly increased in both human subjects with alcoholic hepatitis and in mice exposed to alcohol administrated in chronic-binge pattern vs. non drinking controls. In ethanol-treated mice, the hepatic and adipose expression of FGF-21 were increased by both mRNA and protein levels. The increased FGF-21 expression was positively correlated with increased hepatic levels of triglyceride and serum levels of free fatty acids. Alcohol increased FGF-21 expression in hepato-cytes in a time- and dose-dependent manner. The expression of PGC-1α and Rev-Erbα,

learn more which are important transcription suppressors of FGF-21, were decreased in mouse livers exposed to alcohol. Conclusions: Alcohol exposure increased hepatic and circulating FGF-21 expression likely through an inhibition of transcriptional suppression mediated by the PGC-1α-Rev-Erbα pathway. The regulation of FGF-21 expression may be associated with hepatic lipid metabolism in alcoholic steatohepatitis. The observed increase in circulating FGF-21 was conserved between animal models and human subjects with alcoholic hepatitis. Altered FGF-21 metabolism plays an etiologic role in the development/progression of alcoholic liver disease. Disclosures: Craig J. McClain – Consulting: Vertex, Gilead, Baxter, Celgene, Nestle, Danisco, Abbott, Genentech; Grant/Research Support: Ocera,

Merck, Glaxo SmithKline; Speaking and Teaching: Roche The following people have nothing to disclose: GSK-3 inhibitor Wenke Feng, Yanlong Liu, Cuiqing Zhao, Keith C. Falkner, Mohammad K. Mohammad, Matthew C. Cave Alcohol induced liver disease (ALD) is a leading cause of chronic liver disease worldwide and its pathogenesis remains poorly understood. ALD comprises a spectrum of disorders starting from steatosis that can progress to alcoholic steatohepatitis (ASH), characterized by liver injury, inflammation and fibrosis. To better understand the transition from

alcohol-induced steatosis to ASH adequate experimental models are needed. The Lieber-DeCarli (L-DC) ethanol liquid diet and binge drinking are among the most common approaches of MCE公司 chronic and acute alcohol drinking but their impact in ALD is moderate. Since cholesterol has emerged as a critical factor in the progression from steatosis to NASH, we hypothesized that cholesterol supplementation may synergize with alcohol to cause ASH. Thus, our aim was to test if cholesterol aggravates liver disease in chronic and binge models of ALD. Methods: Mice were fed a standard or modified L-DC ethanol liquid diet (Dyets, Inc) containing corn oil (Coil, 35% calories) with or without cholesterol (Chol, 0.2%) for 4 weeks. In addition, mice fed with a high cholesterol diet (HC, 1%) or Lombardi diet (LD, choline-deficient) for 2%ndash;3 days were gavaged with ethanol (3g/kg) every 12 hours for 3 days. Samples were processed to examine steatosis, liver injury, inflammatory and fibrotic markers by histology, IHC and RT-PCR.