Arsov, TodorLarter, ClaireNolan, ChristopherPetrovsky, NikolaiGoodnow, ChristopherTeoh, NarcissusYeh, MatthewFarrell, Geoffrey2015-12-100006-291Xhttp://hdl.handle.net/1885/57406The biochemical differences between simple steatosis, a benign liver disease, and non-alcoholic steatohepatitis, which leads to cirrhosis, are unclear. Fat aussie is an obese mouse strain with a truncating mutation (foz) in the Alms1 gene. Chow-fed female foz/foz mice develop obesity, diabetes, and simple steatosis. We fed foz/foz and wildtype mice a high-fat diet. Foz/foz mice developed serum ALT elevation and severe steatohepatitis with hepatocyte ballooning, inflammation, and fibrosis; wildtype mice showed simple steatosis. Biochemical pathways favoring hepatocellular lipid accumulation (fatty acid uptake; lipogenesis) and lipid disposal (fatty acid β-oxidation; triglyceride egress) were both induced by high-fat feeding in wildtype but not foz/foz mice. The resulting extremely high hepatic triglyceride levels were associated with induction of mitochondrial uncoupling protein-2 and adipocyte-specific fatty acid binding protein-2, but not cytochrome P4502e1 or lipid peroxidation. In this model of metabolic syndrome, transition of steatosis to steatohepatitis was associated with hypoadiponectinemia, a mediator of hepatic fatty acid disposal pathways.Keywords: adiponectin; alanine aminotransferase; cytochrome P450 2E1; fatty acid; fatty acid binding protein; lipid peroxide; microsomal triglyceride transfer protein; saturated fatty acid; triacylglycerol; uncoupling protein 2; adipocyte; alanine aminotransferase Adiponectin; Hepatic lipid partitioning; Lipotoxicity; Metabolic syndrome; Non-alcoholic steatohepatitis200610.1016/j.bbrc.2006.02.0322015-12-09