title: Longitudinal analysis of murine steatohepatitis model induced by chronic exposure to high-fat diet.
abstract: 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 long-term 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 TNFalpha and type I collagen alpha1 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.
authors.affiliation: Tsukuba Research Institute, Pharmaceutical Co., Ltd, Tsukuba, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ito
authors.forename: Jun
authors.initials: J
authors.lastname: Suzuki
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Tsujioka
authors.forename: Minoru
authors.initials: M
authors.lastname: Sasaki
authors.forename: Akira
authors.initials: A
authors.lastname: Gomori
authors.forename: Takashi
authors.initials: T
authors.lastname: Shirakura
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Hirose
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ito
authors.forename: Akane
authors.initials: A
authors.lastname: Ishihara
authors.forename: Hisashi
authors.initials: H
authors.lastname: Iwaasa
authors.forename: Akio
authors.initials: A
authors.lastname: Kanatani