title: Obesity promotes colonic stem cell expansion during cancer initiation.
abstract: 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.
authors.affiliation: Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, TX, USA.
authors.forename: V
authors.initials: V
authors.lastname: DeClercq
authors.affiliation: Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, TX, USA; Department of Microbial Pathogenesis and Immunology, School of Medicine, Texas A&M University Health Science Center, College Station, TX, USA.
authors.forename: D N
authors.initials: DN
authors.lastname: McMurray
authors.affiliation: Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, TX, USA; Department of Microbial Pathogenesis and Immunology, School of Medicine, Texas A&M University Health Science Center, College Station, TX, USA; Department of Nutrition and Food Science, Texas A&M University, College Station, MS 2253, Cater Mattil, TX 77843-2253, USA; Center for Translational Environmental Health Research, Texas A&M University, College Station, TX, USA. Electronic address: r-chapkin@tamu.edu.
authors.forename: R S
authors.initials: RS
authors.lastname: Chapkin
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000209:etiology* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism
keywords: Adiponectin; Colon cancer; Lgr5 stem cells; Obesity