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Obesity and the Risk of Colon Cancer in Mouse Models
Author(s) -
Sikalidis Angelos,
Fitch Mark D,
Fleming Sharon E
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1013-b
Subject(s) - aberrant crypt foci , colorectal cancer , leptin , azoxymethane , medicine , endocrinology , hyperinsulinemia , carcinogenesis , cancer , obesity , overweight , crypt , biology , insulin resistance , colonic disease
A large body of epidemiological data indicates that obesity increases the risk of colon cancer in humans. There are limited studies using rodent models where the relationship between obesity and colon cancer has been studied. In this study, C57BL/6J ob/ob obese mice (which lack the gene for leptin production), wild‐type diet‐induced obese (DIO) mice and lean wild‐type controls were used to investigate the influence of obesity on the risk of colon cancer. We originally hypothesized that hyperinsulinemia associated with the obese phenotype would be responsible for increased colonic tumorigenesis. Colon cancer was chemically induced by injecting the mice with azoxymathane (AOM) at levels that we experimentally determined to result in equivalent AOM concentrations in circulating blood. Risk of colon cancer was assessed via microscopic examination of colons for aberrant crypts and aberrant crypt foci. In separate experiments, DIO mice were found to have significantly more aberrant crypts and aberrant crypt foci per mouse than wild‐type control mice, supporting the epidemiological data that obesity increases risk of colonic tumorigenesis. By contrast, obese ob/ob mice had fewer aberrant crypt foci than did their wild‐type control littermates. Thus, even though both obese models exhibit increased body fatness and hyperinsulinemia, only the leptin‐competent model exhibited increased risk of colon cancer. The results of these experiments suggest that leptin (a hormone and cytokine which acts as a satiety regulator) may be the critical molecule responsible for the increased risk of colon cancer for overweight and obese humans. FUNDING: NIH, NCI R03CA95974; and the Agriculture Experiment Station