Obesity enhances gastrointestinal tumorigenesis in Apc-mutant mice

C. Gravaghi, J. Bo, K. M.D. LaPerle, F. Quimby, R. Kucherlapati, W. Edelmann, S. A. Lamprecht

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Epidemiological evidence indicates a link between obesity and human colon cancer. A putative association between obesity and colon tumorigenesis has been explored experimentally using chemical carcinogens administered to obese rodents. The main objective of this study was to generate a new mouse line that displays both obesity and intestinal tumorigenesis. To this end, we have generated C57BLKS-mLeprdb/db; Apc1638N/+ mice combining both db and Apc mutations. The db mutation results in obesity and type 2 diabetes, the Apc mutation is a key initiating event of intestinal neoplasia. All mice were euthanized at 6 months of age and all regions of the gastrointestinal tract examined for tumors. The results show that the combination of Apc1638N/+ and db mutations not only enhanced mutant Apc-driven small intestinal tumorigenesis but also induced gastric and colonic tumors. Homozygous db mice did not develop gastrointestinal neoplasia. These findings indicate that obesity associated with type 2 diabetes promotes gastrointestinal tumorigenesis in Apc-deficient mice and provides evidence of a mechanistic link between obesity and colorectal neoplasia.

Original languageEnglish (US)
Pages (from-to)1716-1719
Number of pages4
JournalInternational Journal of Obesity
Volume32
Issue number11
DOIs
StatePublished - Nov 1 2008

Keywords

  • Apc
  • Colon cancer
  • Diabetes
  • db/db

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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    Gravaghi, C., Bo, J., LaPerle, K. M. D., Quimby, F., Kucherlapati, R., Edelmann, W., & Lamprecht, S. A. (2008). Obesity enhances gastrointestinal tumorigenesis in Apc-mutant mice. International Journal of Obesity, 32(11), 1716-1719. https://doi.org/10.1038/ijo.2008.149