Adiponectin suppresses colorectal carcinogenesis under the high-fat diet condition.

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.

• Authors: T Fujisawa, H Endo, A Tomimoto, M Sugiyama, H Takahashi, S Saito, M Inamori, N Nakajima, M Watanabe, N Kubota, T Yamauchi, T Kadowaki, K Wada, H Nakagama, A Nakajima
• Journal: Gut (Gut) Vol. 57 Issue 11 Pg. 1531-8 (Nov 2008) ISSN: 1468-3288 [Electronic] England
• PMID: 18676419 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adiponectin
• Dietary Fats
• Receptors, Adiponectin
• Protein Kinases
• mTOR protein, mouse
• TOR Serine-Threonine Kinases
• AMP-Activated Protein Kinase Kinases
• Azoxymethane

Topics

• AMP-Activated Protein Kinase Kinases
• Adiponectin (deficiency)
• Animals
• Apoptosis (physiology)
• Azoxymethane
• Blotting, Western
• Cell Proliferation
• Cell Transformation, Neoplastic (chemically induced, metabolism)
• Colonic Polyps (etiology, pathology)
• Colorectal Neoplasms (etiology, pathology, physiopathology)
• Dietary Fats (administration & dosage, adverse effects)
• Intestinal Mucosa (cytology, metabolism)
• Mice
• Mice, Knockout
• Obesity (metabolism, physiopathology)
• Precancerous Conditions (chemically induced, etiology, pathology)
• Protein Biosynthesis (physiology)
• Protein Kinases (metabolism)
• Receptors, Adiponectin (deficiency)
• TOR Serine-Threonine Kinases