Obesity enhances gastrointestinal tumorigenesis in Apc-mutant mice

Int J Obes (Lond). 2008 Nov;32(11):1716-9. doi: 10.1038/ijo.2008.149. Epub 2008 Aug 26.


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-mLepr(db/db); Apc(1638N/+) 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 Apc(1638N/+) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology*
  • Gastrointestinal Tract / pathology
  • Genes, APC
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Obesity / genetics
  • Obesity / pathology*