Obesity enhances gastrointestinal tumorigenesis in Apc-mutant mice

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

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 2008

Fingerprint

Carcinogenesis
Obesity
Mutation
Neoplasms
Type 2 Diabetes Mellitus
Carcinogens
Colonic Neoplasms
Gastrointestinal Tract
Rodentia
Stomach
Colon

Keywords

  • Apc
  • Colon cancer
  • db/db
  • Diabetes

ASJC Scopus subject areas

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

Cite this

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

Obesity enhances gastrointestinal tumorigenesis in Apc-mutant mice. / Gravaghi, C.; Bo, J.; LaPerle, K. M D; Quimby, F.; Kucherlapati, R.; Edelmann, Winfried; Lamprecht, S. A.

In: International Journal of Obesity, Vol. 32, No. 11, 11.2008, p. 1716-1719.

Research output: Contribution to journalArticle

Gravaghi, C, Bo, J, LaPerle, KMD, Quimby, F, Kucherlapati, R, Edelmann, W & Lamprecht, SA 2008, 'Obesity enhances gastrointestinal tumorigenesis in Apc-mutant mice', International Journal of Obesity, vol. 32, no. 11, pp. 1716-1719. https://doi.org/10.1038/ijo.2008.149
Gravaghi, C. ; Bo, J. ; LaPerle, K. M D ; Quimby, F. ; Kucherlapati, R. ; Edelmann, Winfried ; Lamprecht, S. A. / Obesity enhances gastrointestinal tumorigenesis in Apc-mutant mice. In: International Journal of Obesity. 2008 ; Vol. 32, No. 11. pp. 1716-1719.
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