RT Journal Article SR Electronic T1 Adiponectin suppresses colorectal carcinogenesis under the high-fat diet condition JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 1531 OP 1538 DO 10.1136/gut.2008.159293 VO 57 IS 11 A1 T Fujisawa A1 H Endo A1 A Tomimoto A1 M Sugiyama A1 H Takahashi A1 S Saito A1 M Inamori A1 N Nakajima A1 M Watanabe A1 N Kubota A1 T Yamauchi A1 T Kadowaki A1 K Wada A1 H Nakagama A1 A Nakajima YR 2008 UL http://gut.bmj.com/content/57/11/1531.abstract AB Background and 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 a high-fat diet. However, no difference was observed between wild-type and adiponectin-deficient mice fed a 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 a high-fat diet; however, no difference was observed between wild-type and adiponectin-deficient mice fed a 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 the mammalian target of the rapamycin pathway under a high-fat diet, but not under a basal diet. These studies indicate a novel mechanism of suppression of colorectal carcinogenesis induced by a Western-style high-fat diet.