脂肪肝マウス(FLS)にLep[ob]遺伝子を移入した新規コンジェニック系統におけるインスリン抵抗,脂肪性肝炎と肝臓癌
スポンサーリンク
概要
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In order to examine the influence of obesity on metabolic disorder and liver pathogenesis of the Fatty Liver Shionogi (FLS) mouse, which develops hereditary fatty liver and spontaneous liver tumors, we established a new congenic strain named FLS-Lepob. The Lepob gene of the C57BL/6JWakShi (B6)-Lepob/Lepob mouse was transferred into the genome of the FLS mouse, by backcross mating. FLS-Lepob/Lepob mice were maintained by intercrossing between Lepob-heterozygous littermates. The FLS-Lepob/Lepob mice of both sexes developed remarkable hyperphagia, obesity and type 2 diabetes mellitus. At 12 weeks of age, glucosuria was detected in all male and female FLS-Lepob/Lepob mice. Biochemical examination demonstrated that the FLS-Lepob/Lepob mice have severe hyperlipidemia and hyperinsulinemia. The livers of FLS-Lepob/Lepob mice showed microvesicular steatosis and deposition of large lipid droplets in hepatocytes throughout the lobules. The steatohepatitis-like lesions including the multifocal mononuclear cell infiltration and clusters of foamy cells were observed earlier in FLS-Lepob/ Lepob mice than in FLS mice. B6-Lepob/Lepob mice did not show hepatic inflammatory change. Furthermore, FLS-Lepob/Lepob mice developed multiple hepatic tumors including hepatocellular adenomas and carcinomas following steatohepatitis. In conclusion, the FLS-Lepob/Lepob mice developed steatohepatitis and hepatic tumors following hepatic steatosis. The FLS-Lepob/Lepob mouse with obesity and type 2 diabetes mellitus might be a useful animal model for human non-alcoholic steatohepatitis (NASH).
著者
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MAKINO Susumu
Aburahi Laboratories Shionogi Research Laboratories
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Makino Susumu
Aburahi Laboratories Shionogi & Co. Ltd.
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INAGAKI Shuichiro
Discovery Research Laboratories, Shionogi Company
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Inagaki Shuichiro
Discovery Research Laboratories Shionogi Company
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SOGA Masahiko
Discovery Research Laboratories, Shionogi & Co., Ltd.
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HASHIMOTO Setsuko
Developmental Research Laboratories, Shionogi & Co., Ltd.
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KISHIMOTO Yoshio
Aburahi Laboratories, Shionogi & Co., Ltd.
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HIRASAWA Tsutomu
Developmental Research Laboratories, Shionogi & Co., Ltd.
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HASHIMOTO Setsuko
Developmental Research Laboratories, Shionogi & Co., Ltd.
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曽我 正彦
Discovery Research Laboratories, Shionogi & Co., Ltd.
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橋本 世津子
Developmental Research Laboratories, Shionogi & Co., Ltd.
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岸本 嘉夫
Aburahi Laboratories, Shionogi & Co., Ltd.
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INAGAKI Shuichiro
Discovery Research Laboratories, Shionogi & Co., Ltd.
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HIRASAWA Tsutomu
Developmental Research Laboratories, Shionogi & Co., Ltd.
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KISHIMOTO Yoshio
Aburahi Laboratories, Shionogi & Co., Ltd.
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SOGA Masahiko
Discovery Research Laboratories, Shionogi & Co., Ltd.
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MAKINO Susumu
Aburahi Laboratories, Shionogi & Co., Ltd.
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- 脂肪肝マウス(FLS)にLep[ob]遺伝子を移入した新規コンジェニック系統におけるインスリン抵抗,脂肪性肝炎と肝臓癌
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