High Fat Diet Blunts the Activation of Canonical Wnt Signaling Pathway Induced by Radiation Therapy in Mouse Colon Epithelia

Background Radiation stimulates multiple metabolic pathways in colon epithelial cells in mice, including the Wnt signaling pathway. Activation of Wnt/β‐catenin pathway was indicated to increase resistance to radiation therapy. On the other hand, we have shown that long‐term consumption of high fat diet inhibits Wnt signaling through the down‐regulation of β‐catenin expression in colon. Objectives The main goal of this present study is to examine the impact from high fat diet on the expression of genes involved in the Wnt/β‐catenin pathway on colon epithelial in mice exposed to radiation. Methods In this study, 5‐week‐old male mice were fed either a control diet (n=22, 10% kcal fat) or a high‐fat diet (n=24, 45% kcal fat) for 11 weeks. Half of the mice were sampled as pre‐irradiation (Pre‐CON and Pre‐HF). The rest of the mice were treated with a single dose of radiation at 3 Gy (IR‐CON and IR‐HF) and tissue collection was conducted after 4 more weeks of respective dietary treatments. mRNA expression of Wnt pathway genes were analyzed in the colon tissue. Results Radiation significantly increased mRNA expression of canonical Wnt signaling related genes including APC, AXIN1, CTNNB1 (β‐catenin) and cMyc in IR‐CON comparing to Pre‐CON (p<0.05). On the other hand, APC, AXIN1 and cMyc remain unchanged in IR‐HF comparing to Pre‐HF, only CTNNB1 increased. Sfrp2, a Wnt signaling antagonist, was significantly increased in IR‐HF comparing to Pre‐HF (p<0.05), while remained unchanged in IR‐CON comparing to Pre‐CON. Furthermore, mRNA expression of a cell cycle control gene, p21, was significantly increased in IR‐HF. This is accompanied with a significant decrease of CyclinD1 expression (p<0.05, when comparing to Pre‐HF). Conclusion Overall, analysis of mRNA expression suggests that high fat diet blunts the effects of radiation on inducing the Wnt signaling pathway, which is associated with cell cycle pathway in mouse colon epithelia. Our study shows that high fat diet may interfere with radiation treatment in colon. Support or Funding Information This project was supported in part by the Campus Research Board of University of Illinois at Urbana‐Champaign and the USDA Cooperative State Research, Education and Extension Service, Hatch project numbers # ILLU‐698‐923 and ILLU‐698‐379 to H.C. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .