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

The Journal of Veterinary Medical Science

Yasufumi TORINIWA¹  Tomoyuki SAITO²  Katsuhiro MIYAJIMA³  Yukihito ISHII⁴ 

[1] 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;Kyoto University, Graduate School of Agriculture, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan;Laboratory of Animal Genetics, Graduate School of Science and Technology, Niigata University, 2-8050 Ikarashi, Nishi-ku, Niigata 950-2181, Japan

关键词: metformin;    NASH;    pioglitazone;    SDT fatty rat;   

DOI  :  10.1292/jvms.18-0119

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

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.

【 授权许可】

Unknown