1. Adiponectin suppresses colorectal carcinogenesis under the high-fat diet condition.
- Author
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Fujisawa, T., Endo, H., Tomimoto, A., Sugiyama, M., Takahashi, H., Saito, S., Inamori, M., Nakajima, N., Watanabe, M., Kubota, N., Yamauchi, T., Kadowaki, T., Wada, K., Nakagama, H., and Nakajima, A.
- Subjects
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COLON cancer , *FAT cells , *ADIPOSE tissues , *HIGH-carbohydrate diet , *SUPPRESSOR cells , *IMMUNOSUPPRESSION , *LABORATORY mice - Abstract
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 defi- ciency. 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. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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