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Animal Bioresource in Japan

.: Home > Animal Bioresource in Japan > 2010 > Volume 59 Number 4 > Masahiko SOGA1), Setsuko HASHIMOTO2), Yoshio KISHIMOTO3), Tsutomu HIRASAWA2), Susumu MAKINO3)5) and Shuichiro INAGAKI4)

Insulin Resistance, Steatohepatitis, and Hepatocellular Carcinoma in a New Congenic Strain of Fatty Liver Shionogi (FLS) Mice with the Lepob Gene

Masahiko SOGA1), Setsuko HASHIMOTO2), Yoshio KISHIMOTO3), Tsutomu HIRASAWA2), Susumu MAKINO3)5) and Shuichiro INAGAKI4)
1) Discovery Research Laboratories, Shionogi & Co., Ltd. 2) Developmental Research Laboratories, Shionogi & Co., Ltd. 3) Aburahi Laboratories, Shionogi & Co., Ltd. 4) Discovery Research Laboratories, Shionogi & Co., Ltd. 5) KAC Co., Ltd.
Abstract :

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).

Keywords :
FLS-Lepob/Lepob mouse, hepatocellular carcinoma, insulin resistance, non-alcoholic steatohepsatitis, obesity

Date Deposited : 21 Jun 2011 14:26

Last Modified : 21 Jun 2011 14:26

Official URL: http://www.jstage.jst.go.jp/browse/expanim/60/1/_contents

Volume 59, Number 4, - 2010

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