| First Author | Arsov T | Year | 2006 |
| Journal | Biochem Biophys Res Commun | Volume | 342 |
| Issue | 4 | Pages | 1152-9 |
| PubMed ID | 16516152 | Mgi Jnum | J:107058 |
| Mgi Id | MGI:3620255 | Doi | 10.1016/j.bbrc.2006.02.032 |
| Citation | Arsov T, et al. (2006) Adaptive failure to high-fat diet characterizes steatohepatitis in Alms1 mutant mice. Biochem Biophys Res Commun 342(4):1152-9 |
| abstractText | The 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 beta-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. |
