title: Loss of adiponectin promotes intestinal carcinogenesis in Min and wild-type mice.
abstract: OBJECTIVE
  Metabolic syndrome- and obesity-associated cancers, including colon cancer, are common in Western countries. Visceral fat accumulation and decreased levels of plasma adiponectin (APN) have been associated with development of human colorectal adenoma. We investigated the function of APN in intestinal carcinogenesis.
  
  
  METHODS
  APN+/+, APN+/-, or APN-/- mice (C57BL/6J) were given injections of azoxymethane (AOM), which led to development of intestinal tumors; these strains of mice were also crossed with Min mice to assess polyp formation. Adipocytokine levels and phosphorylation/activation of AMP-activated protein kinase (AMPK) were evaluated to investigate the mechanisms of APN in tumor growth.
  
  
  RESULTS
  The total number of polyps in the intestines of male APN+/-Min and APN-/-Min mice increased 2.4- and 3.2-fold, respectively, by the age of 9 weeks and 3.2- and 3.4-fold, respectively, by 12 weeks, compared with those of APN+/+Min mice. Similar results were obtained from female mice. AOM induced colon tumor formation in 40% of APN+/+, 50% of APN+/-, and 71% of APN-/- (P<.05) mice, respectively; mean values for tumor multiplicity of each genotype were 0.5, 0.6, and 1.1 (P<.05), respectively. Phosphorylation of AMPK decreased in intestinal epithelial cells of APN-/- mice compared with APN+/+ mice. Among serum adipocytokines, plasminogen activator inhibitor-1 levels increased in APN-/-Min mice and APN-/- mice that received injections of AOM. Activation of AMPK suppressed expression of plasminogen activator inhibitor-1 in Min mice.
  
  
  CONCLUSIONS
  Mice with disruptions in APN develop more intestinal tumors and have decreased activation (phosphorylation) of AMPK and increased levels of plasminogen activator inhibitor-1, compared with wild-type mice. APN and its receptor might be developed as targets for cancer chemopreventive agents.
authors.affiliation: Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Tokyo, Japan. mimutoh@ncc.go.jp
authors.forename: Michihiro
authors.initials: M
authors.lastname: Mutoh
authors.forename: Naoya
authors.initials: N
authors.lastname: Teraoka
authors.forename: Shinji
authors.initials: S
authors.lastname: Takasu
authors.forename: Mami
authors.initials: M
authors.lastname: Takahashi
authors.forename: Kunishige
authors.initials: K
authors.lastname: Onuma
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Naoto
authors.initials: N
authors.lastname: Kubota
authors.forename: Takamoto
authors.initials: T
authors.lastname: Iseki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugimura
authors.forename: Keiji
authors.initials: K
authors.lastname: Wakabayashi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D011125:Adenomatous Polyposis Coli / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D052242:Adiponectin / Q000172:deficiency / Q000235:genetics; D000818:Animals; D001397:Azoxymethane; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D003111:Colonic Polyps / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D004789:Enzyme Activation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D015398:Signal Transduction; D013997:Time Factors; D047368:Tumor Burden; D015854:Up-Regulation
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D017395:Plasminogen Activator Inhibitor 1; D055372:AMP-Activated Protein Kinases; D001397:Azoxymethane