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Publication : Obesity promotes colonic stem cell expansion during cancer initiation.

First Author  DeClercq V Year  2015
Journal  Cancer Lett Volume  369
Issue  2 Pages  336-43
PubMed ID  26455770 Mgi Jnum  J:226621
Mgi Id  MGI:5697993 Doi  10.1016/j.canlet.2015.10.001
Citation  DeClercq V, et al. (2015) Obesity promotes colonic stem cell expansion during cancer initiation. Cancer Lett 369(2):336-43
abstractText  There is an urgent need to elucidate the mechanistic links between obesity and colon cancer. Convincing evidence for the role of Lgr5(+) stem cells in colon tumorigenesis has been established; however, the influence of obesity on stem cell maintenance is unknown. We assessed the effects of high fat (HF) feeding on colonic stem cell maintenance during cancer initiation (AOM induced) and the responsiveness of stem cells to adipokine signaling pathways. The number of colonic GFP(+) stem cells was significantly higher in the AOM-injected HF group compared to the LF group. The Lgr5(+) stem cells of the HF fed mice exhibited statistically significant increases in cell proliferation and decreases in apoptosis in response to AOM injection compared to the LF group. Colonic organoid cultures from lean mice treated with an adiponectin receptor agonist exhibited a reduction in Lgr5-GPF(+) stem cell number and an increase in apoptosis; however, this response was diminished in the organoid cultures from obese mice. These results suggest that the responsiveness of colonic stem cells to adiponectin in diet-induced obesity is impaired and may contribute to the stem cell accumulation observed in obesity.
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