We showed recently that diabetic and mildly obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats were more susceptible to azoxymethane-induced carcinogenesis than control Long-Evans Tokushima Otsuka (LETO) rats, and carcinogenesis was inhibited by 20% caloric restriction (CR) and enhanced by high-fat diet (HFD, control diet with 10% safflower oil). To elucidate the mechanism of cancer susceptibility, we performed serum biochemical analysis and microarray analysis of the liver and colonic mucosa. Male LETO and OLETF rats were given control diet, 20% CR diet or HFD for 5 weeks, and euthanized at 24 weeks of age (n=5, respectively). In both strains, blood glucose, serum triglyceride, total cholesterol, insulin and leptin levels decreased by 20% CR, and increased by HFD. Steatosis of hepatocytes in OLETF rats was ameliorated by 20% CR and enhanced by HFD. Microarray analysis of the liver showed that 20% CR up-regulated metallothionein 1A gene, and down-regulated heat shock 105kDa/110kDa protein 1 (Hsph1) and heat shock 70kDa protein 1B (Hspa1b) genes in both strains. There were no histological differences in the colonic mucosa in both strains and the effect of the dietary difference was not found. Microarray analysis of the colonic mucosa showed that 20% CR down-regulated Hsph1 and Hspa1b genes, and HFD up-regulated fatty acid binding protein 2 in both strains. These data suggest that hyperinsulinemia, hyperlipidemia and oxidative stress by overnutrition exert significant role in cancer susceptibility in OLETF rats.

Citation Format: Keisuke Izumi, Chie Takasu, Tetsuyuki Takahashi, Hisanori Uehara. Serum biochemistry and microarray analysis of liver and colonic mucosa in LETO and diabetic OLETF rats treated with 20% caloric restriction and high-fat diet. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1279. doi:10.1158/1538-7445.AM2013-1279