title: Elevated circulating adiponectin and elevated insulin sensitivity in adiponectin transgenic mice are not associated with reduced susceptibility to colon carcinogenesis.
abstract: Obesity, particularly visceral adiposity, is an established risk factor for colorectal cancer (CRC) and this is thought to result, at least in part, from insulin resistance and chronic hyperinsulinemia that may be mediated by adipokines. Serum levels of adiponectin, the most abundant protein secreted from adipocytes, are decreased in obesity and are inversely associated with insulin resistance and hyperinsulinemia. The objective of this study was to determine whether elevated circulating adiponectin plays a role in colon carcinogenesis using adiponectin transgenic (AdTg) mice that have 2-3-fold elevated circulating adiponectin but similar body weights as wildtype (WT) littermates used as controls. Eight-week old male and female AdTg and WT mice were treated with 4 weekly injections of the colon-specific carcinogen azoxymethane (AOM). One week following the last dose of AOM, all mice were placed on a high-fat diet and killed 24 weeks later, at 36 weeks of age, for the analysis of colon tumors. Glucose tolerance tests (GTT) were performed by injecting 2g/kg dextrose or 1.25-1.5 g/kg dextrose into all 12-week and 32-35-week-old mice respectively, and measuring blood from the tail vein 15, 30, 60 and 120 min following glucose administration. There were no significant differences in colon tumor incidence, number or size between AdTg and WT mice of either sex. AdTg mice of both sexes displayed resistance to diet-induced decreases in insulin sensitivity. Our results show that constitutively elevated levels of circulating adiponectin in AdTg mice do not confer protection against the development of colon tumors.
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Kafi N
authors.initials: KN
authors.lastname: Ealey
authors.forename: Michael C
authors.initials: MC
authors.lastname: Archer
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D002478:Cells, Cultured; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D004198:Disease Susceptibility; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D015430:Weight Gain
chemical_list: D052242:Adiponectin; D002273:Carcinogens; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D001397:Azoxymethane