TY - JOUR
T1 - Early lesion formation in colorectal carcinogenesis is associated with adiponectin status whereas neoplastic lesions are associated with diet and sex in C57BL/6J mice
AU - Boddicker, Rebecca L.
AU - Whitley, Elizabeth
AU - Birt, Diane F.
AU - Spurlock, Michael E.
N1 - Funding Information:
This work was supported by National Institute of Food and Agriculture, U.S. Department of Agriculture [3411519743, 2009] to the Nutrition and Wellness Research Center, Iowa State University.
PY - 2011/11/1
Y1 - 2011/11/1
N2 - Adiponectin is an antiinflammatory and insulin-sensitizing hormone that is decreased in obesity. Although controversial, it has been suggested that decreased adiponectin contributes to colorectal cancer risk in obesity. To further investigate the role of adiponectin in obesity-linked colorectal carcinogenesis, we used male and female adiponectin knockout (KO) and wild-type (Wt) C57BL/6J mice. Tumorigenesis was induced in all mice with the combined treatment of azoxymethane (AOM) and dextran sodium sulfate (DSS). Following AOM/DSS treatment, mice were fed a low-fat control (LFC), or high-fat lard (HFL) diet for 7 1/2 wk. KO mice developed fewer total lesions than Wt mice, males developed fewer lesions than females, and mice fed the HFL diet developed fewer lesions than those fed the LFC diet. Early lesion multiplicity was influenced by genotype, whereas advanced lesion development was influenced by sex and diet. Moreover, lesion types were differentially correlated with serum adipokines and colon gene expression of adiponectin receptors, insulin receptor, and toll-like receptor 4. These data suggest that in the AOM/DSS model of carcinogenesis, adiponectin functions to promote early lesion development whereas sex and diet are important regulators of advanced lesion development through pathways involved in inflammation and insulin signaling.
AB - Adiponectin is an antiinflammatory and insulin-sensitizing hormone that is decreased in obesity. Although controversial, it has been suggested that decreased adiponectin contributes to colorectal cancer risk in obesity. To further investigate the role of adiponectin in obesity-linked colorectal carcinogenesis, we used male and female adiponectin knockout (KO) and wild-type (Wt) C57BL/6J mice. Tumorigenesis was induced in all mice with the combined treatment of azoxymethane (AOM) and dextran sodium sulfate (DSS). Following AOM/DSS treatment, mice were fed a low-fat control (LFC), or high-fat lard (HFL) diet for 7 1/2 wk. KO mice developed fewer total lesions than Wt mice, males developed fewer lesions than females, and mice fed the HFL diet developed fewer lesions than those fed the LFC diet. Early lesion multiplicity was influenced by genotype, whereas advanced lesion development was influenced by sex and diet. Moreover, lesion types were differentially correlated with serum adipokines and colon gene expression of adiponectin receptors, insulin receptor, and toll-like receptor 4. These data suggest that in the AOM/DSS model of carcinogenesis, adiponectin functions to promote early lesion development whereas sex and diet are important regulators of advanced lesion development through pathways involved in inflammation and insulin signaling.
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U2 - 10.1080/01635581.2011.606954
DO - 10.1080/01635581.2011.606954
M3 - Article
C2 - 21958077
AN - SCOPUS:84857304412
SN - 0163-5581
VL - 63
SP - 1297
EP - 1306
JO - Nutrition and cancer
JF - Nutrition and cancer
IS - 8
ER -