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Adiponectin suppresses colorectal carcinogenesis under the high-fat diet condition
  1. T Fujisawa1,
  2. H Endo1,
  3. A Tomimoto1,
  4. M Sugiyama1,
  5. H Takahashi1,
  6. S Saito1,
  7. M Inamori1,
  8. N Nakajima2,
  9. M Watanabe3,
  10. N Kubota4,
  11. T Yamauchi4,
  12. T Kadowaki4,
  13. K Wada5,
  14. H Nakagama6,
  15. A Nakajima1
  1. 1
    Division of Gastroenterology, Yokohama City University School of Medicine, Yokohama, Japan
  2. 2
    Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan
  3. 3
    Laboratory for Medical Engineering, Graduate School of Engineering, Yokohama National University, Yokohama, Japan
  4. 4
    Department of Internal Medicine, Graduate school of Medicine, University of Tokyo, Tokyo, Japan
  5. 5
    Department of Pharmacology, Graduate School of Dentistry, Osaka University, Osaka, Japan
  6. 6
    Biochemistry Division, National Cancer Center Research Institute, Tokyo, Japan
  1. Dr A Nakajima, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; Nakajima-tky{at}umin.ac.jp

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 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.

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Footnotes

  • ▸ Additional figures and tables are published online only at http://gut.bmj.com/content/vol57/issue11

  • Funding: This work was supported in part by a Grant-in-Aid for research on the Third Term Comprehensive Control Research for Cancer from the Ministry of Health, Labour and Welfare, Japan to AN; a grant from the National Institute of Biomedical Innovation (NBIO) to AN; a grant from the Ministry of Education, Culture, Sports, Science and Technology, Japan (KIBAN-B) to AN; and a research grant of the Princess Takamatsu Cancer Research Fund.

  • Competing interests: None.

  • Ethics approval: All animal experiments were approved by the institutional Animal Care and Use Committee of Yokohama City University School of Medicine.

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