Investigation of pharmacological responses to anti-diabetic drugs in female          Spontaneously Diabetic Torii (SDT) fatty rats, a new nonalcoholic steatohepatitis (NASH)          model

Yasufumi TORINIWA; Tomoyuki SAITO; Katsuhiro MIYAJIMA; Yukihito ISHII; Kinuko UNO; Tatsuya MAEKAWA; Tohru MATSUI; Shinichi KUME; Takahisa YAMADA; Takeshi OHTA

doi:10.1292/jvms.18-0119

Laboratory Animal Science

Investigation of pharmacological responses to anti-diabetic drugs in female Spontaneously Diabetic Torii (SDT) fatty rats, a new nonalcoholic steatohepatitis (NASH) model

Yasufumi TORINIWA, Tomoyuki SAITO, Katsuhiro MIYAJIMA, Yukihito ISHII, Kinuko UNO, Tatsuya MAEKAWA, Tohru MATSUI, Shinichi KUME, Takahisa YAMADA, Takeshi OHTA

Author information

Yasufumi TORINIWA
Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan
Tomoyuki SAITO
Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan
Katsuhiro MIYAJIMA
Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan
Department of Nutritional Science and Food Safety, Faculty of Applied Biosciences, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan
Yukihito ISHII
Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan
Kinuko UNO
Department of Nutritional Science and Food Safety, Faculty of Applied Biosciences, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan
Tatsuya MAEKAWA
Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan
Tohru MATSUI
Kyoto University, Graduate School of Agriculture, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan
Shinichi KUME
Kyoto University, Graduate School of Agriculture, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan
Takahisa YAMADA
Laboratory of Animal Genetics, Graduate School of Science and Technology, Niigata University, 2-8050 Ikarashi, Nishi-ku, Niigata 950-2181, Japan
Takeshi OHTA
Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan

Keywords: metformin, NASH, pioglitazone, SDT fatty rat

JOURNAL FREE ACCESS

2018 Volume 80 Issue 6 Pages 878-885

DOI https://doi.org/10.1292/jvms.18-0119

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Abstract

Nonalcoholic steatohepatitis (NASH) is a progressive liver disease, and some patients develop hepatic cirrhosis/carcinoma. Animal models play key roles in the development of new therapies for NASH. In this study, the pharmacological effects of metformin and pioglitazone were investigated in female Spontaneously Diabetic Torii (SDT) fatty rats to verify the utility of this model. The anti-diabetic drugs were administered to SDT fatty rats fed a cholesterol-enriched diet from 4 to 25 weeks, and changes in food intake, body weight, and blood chemistry parameters were evaluated every 4 weeks. The hepatic lipid content, mRNA expression in relation to lipid synthesis, inflammation, and fibrosis, and histopathological analyses were performed at 25 weeks. Pioglitazone improved hyperglycemia, hyperlipidemia, and abnormalities in hepatic parameters. The insulin levels were lower than those in the control rats before 16 weeks. Plasma glucose levels in the metformin-treated rats were lower than those in the control rats, and plasma alanine aminotransferase levels temporarily decreased. The lipid content and some mRNA expression in relation to fibrosis in the liver decreased with pioglitazone treatment, and the mRNA expression of microsomal triglyceride transfer protein increased. Hepatic fibrosis observed in the SDT fatty rats improved with pioglitazone treatment; however, the effect with metformin treatment was partial. These results in both drugs are in line with results in the human study, suggesting that the SDT fatty rat is useful for developing new anti-NASH drugs that show potential to regulate glucose/lipid metabolism.

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