Longitudinal analysis of murine steatohepatitis model induced by chronic exposure to high-fat diet
Longitudinal analysis of murine steatohepatitis model induced by chronic exposure to high-fat diet
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DOI：
10.1111/j.1872-034x.2007.00008.x
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发表时间：
2007-01-01
影响因子：
4.2
通讯作者：
Kanatani, Akio
中科院分区：
文献类型：
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作者：
Ito, Makoto;Suzuki, Jun;Kanatani, Akio
一些流行病学证据表明，非酒精性脂肪性肝炎（NASH）与人类肥胖密切相关。然而，NASH及其关键代谢异常进展的确切机制仍有待阐明。我们发现，长期高脂饮食（HFD）暴露诱导NASH，小鼠体重超重，高胰岛素血症和高脂血症。模型的纵向分析表明，脂肪性肝炎是在代谢异常发作后诱导的。此外，我们发现MCP-1 mRNA的表达在TNF α和1型胶原α 1 mRNA的诱导之前以及脂肪性肝炎发作之前在肝脏中被诱导。我们证实，在喂食HFD 50周的小鼠中，肝脏MCP-1含量增加，尽管MCP-1在NASH发展中的确切作用仍有待解决。小鼠模型的特征还在于过氧化氢酶活性和谷胱甘肽含量的中度降低，以及肝脏中脂肪酸合成酶、乙酰辅酶A羧化酶1和FAT/CD 36 mRNA的过表达。鼠NASH模型显然模拟了病症的临床方面，并提供了对NASH的深入了解。
Several lines of epidemiological evidence have suggested that non-alcoholic steatohepatitis (NASH) is closely associated with obesity in humans. However, the precise mechanisms of the progression of NASH and its key metabolic abnormalities remain to be elucidated. We found that longterm high-fat diet (HFD) exposure induces NASH, with excess body weight, hyperinsulinemia and hypercholesteremia in mice. Longitudinal analysis of the model showed that steatohepatitis was induced after onset of metabolic abnormalities. In addition, we found that expression of MCP-1 mRNA was induced in the liver before induction of TNF alpha and type 1 collagen alpha 1 mRNAs, and prior to onset of steatohepatitis. We confirmed that hepatic MCP-1 contents were increased in mice fed HFD for 50 weeks, although the precise role of MCP-1 in the development of NASH remains to be addressed. The mouse model was also characterized by moderate reductions in catalase activity and glutathione content, as well as by overexpression of fatty acid synthase, acetyl-CoA carboxylase 1 and FAT/CD36 mRNAs in the liver. The murine NASH model apparently mimics clinical aspects of the condition and provides insight into NASH.