Mo1767 Genetic Deletion of IL-25 Increases Susceptibility to High-Fat Diet-Induced Metabolic Dysfunction in Mice

Abstract

unknown. This study therefore evaluated the effect of the DPP-4 inhibitor, sitagliptin (STG), on diabetes-related colon carcinogenesis in mice. Materials and Methods: Six-week-old male wild-type (WT) and leptin-deficient (ob/ob) C57BL/6J mice were used in this study. The mice received 1,2-dimethlhydrazine (DMH) subcutaneously at a dose of 20 mg/kg body weight three times within a week, and chronic colitis was then induced by administration of two cycles of DSS (each cycle: 3% DSS for 7 days followed by distilled water for 14 days). Sitagliptin (3 mg/kg) was administered to the mice by oral gavage every day during the entire experimental period. The mice were divided into the following three groups: WT group; obob group; and obob+STG group. The mice were sacrificed 28 days after the completion of both cycles of DSS. Results: During the DSS administration cycle, mean body weight decreased significantly in the WT group compared with the obob and obob+STG groups. The disease activity index (DAI) was also increased significantly in the WT group. However, administration of STG did not affect the DAI or body weight. The mean number of tumors was 7.8±4.5, 10.6±3.3, and 6.7±2.4 in the WT, obob, and obob+STG groups, respectively. STG significantly suppressed the occurrence of neoplasia in the obob mice. Mucosal DPP-4 activity and the mucosal concentration of GLP-2 were not significantly different in the three groups. Conclusion: Administration of STG exerts a suppressive effect on the development of colon neoplasia in a murine model of type 2 diabetes. However, STG does not affect the mucosal DPP-4 activity. Because DPP-4 mRNA/DPP-4 activity are highly expressed/detected in the small intestine andDPP-8 and 9 are expressed predominantly in the colon, DPP-4 inhibitors may suppress colon carcinogenesis independent of the GLP pathway.