Background & Aims: The effect of adiponectin on colorectal carcinogenesis has been proposed but not fully investigated. We investigated the effect of adiponectin deficiency on the development of colorectal cancer.
Methods: We generated three types of gene-deficient mice; adiponectin-deficient, Adiponectin receptor 1-deficient and Adiponectin receptor 2-deficient, and investigated chemical-induced colon polyp formation and cell proliferation in colon epithelium. Western blot analysis was performed to elucidate the mechanism which affected colorectal carcinogenesis by adiponectin deficiency.
Results: The numbers of colon polyps were significantly increased in adiponectin-deficient mice compared with wild-type mice fed with high-fat diet. However, no difference was observed between wild-type and adiponectin-deficient mice fed with basal diet. A significant increase in cell proliferative activity was also observed in the colonic epithelium of the adiponectin-deficient mice when compared with wild-type mice fed with high-fat diet, however, no difference was observed between wild-type and adiponectin-deficient mice fed with basal diet. Similarly, an increase in epithelial cell proliferation was observed in Adiponectin receptor 1-deficient mice, but not in Adiponectin receptor 2-deficient mice. Western blot analysis revealed activation of mammalian target of rapamycin, p70 S6 kinase, S6 protein and inactivation of AMP-activated protein kinase in the colon epithelium of adiponectin-deficient mice fed with high-fat diet.
Conclusions: Adiponectin suppresses colonic epithelial proliferation via inhibition of mammalian target of rapamycin pathway under the high-fat diet, but not under basal diet. These studies indicate a novel mechanism of suppression of colorectal carcinogenesis induced by western-style high-fat diet.