title: Development of nonalcoholic steatohepatitis model through combination of high-fat diet and tetracycline with morbid obesity in mice.
abstract: Nonalcoholic steatohepatitis (NASH) is a chronic liver disease closely associated with obesity, type 2 diabetes and hyperlipidemia. For further understanding of NASH, development and characterization of appropriate animal models with metabolic abnormalities is important. Based on the "two hit theory", we tried to develop a new murine model of NASH with metabolic abnormalities. For the first hit to achieve metabolic abnormalities, a high-fat diet (HFD: 60 cal% fat) was fed to C57BL/6 mice for 10 weeks. For the second hit, 30mg/kg tetracycline was injected intraperitoneally once daily for 10 days. The HFD-fed mice treated with tetracycline showed robust increases in triglyceride content and expression levels of proinflammatory cytokine mRNAs in the liver. In addition, plasma ALT levels were significantly elevated by this combinational treatment. Furthermore, histological examination demonstrated that combinational treatment induced multifocal inflammatory cellular infiltration in the livers of all mice, and thus caused mild steatohepatitis. The HFD-tetracycline model could be useful for further understanding NASH.
authors.affiliation: Tsukuba Research Institute, Banyu 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: Minoru
authors.initials: M
authors.lastname: Sasaki
authors.forename: Keiko
authors.initials: K
authors.lastname: Watanabe
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Tsujioka
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Akira
authors.initials: A
authors.lastname: Gomori
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Hirose
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