Adiponectin suppresses colorectal carcinogenesis under the high-fat diet condition.
OBJECTIVE
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.
Fujisawa
T
T
Division of Gastroenterology, Yokohama City University School of Medicine, Yokohama, Japan. Nakajima-tky@umin.ac.jp
Endo
H
H
Tomimoto
A
A
Sugiyama
M
M
Takahashi
H
H
Saito
S
S
Inamori
M
M
Nakajima
N
N
Watanabe
M
M
Kubota
N
N
Yamauchi
T
T
Kadowaki
T
T
Wada
K
K
Nakagama
H
H
Nakajima
A
A
D000091162:AMP-Activated Protein Kinase Kinases; D052242:Adiponectin / Q000172:deficiency*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001397:Azoxymethane; D015153:Blotting, Western; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000378:metabolism; D003111:Colonic Polyps / Q000209:etiology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D011230:Precancerous Conditions / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D014176:Protein Biosynthesis / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000172:deficiency*; D058570:TOR Serine-Threonine Kinases
D052242:Adiponectin; D004041:Dietary Fats; D054419:Receptors, Adiponectin; D011494:Protein Kinases; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D001397:Azoxymethane