OR-026 Exercise induces HIF-1α redistribution in the small intestine

Objective Intestinal epithelial cells are positioned between an anaerobic lumen and a highly metabolic lamina propria, affected by reduced blood flow and tissue hypoxia. Exercise induces blood flow redistribution, leading to hypoperfusion and gastrointestinal (GI) compromise. The hypoxia-inducible factor (HIF) 1α is pivotal in the transcriptional response to oxygen flux. In this study, we hypothesized that exercise induces GI system hypoxia and accumulates HIF-1α. Methods (1) ROSA26 ODD-Luc/+ mouse model (ODD-Luc) was used to detect HIF-1α expression in the intestine (female, 8-week, n=6/group). ODD-Luc mice were randomized into 4 groups: stayed in 21% O2 as the normoxic control (C), exercise (E), injected HIF-1α inhibitor PX-478 before swimming (PS), placed in the chamber containing 9% O2 for 4 hours as the positive control (PC). (2) Exercise models were conducted by volume: Moderate Exercise (ME): mice voluntarily swam for 30 min; Heavy-intensity Exercise (HE): mice swam for 1.5 hours with 5% body weight loads attached to their tails; Long-time Exercise (LE): mice voluntarily swam for 3 hours or till fatigue. Results (1) Exercise increased HIF-1α in the abdominal area. The luciferase activities boosted after exercise, compared to the controls (ME v.s. C, P 0.99; ME v.s. LE, P>0.99; HE v.s. LE, P>0.99); (2) Exercise altered HIF-1α distribution in the small intestine in a time-dependent manner. The expression of HIF-1α was significantly increased after exercise and gradually reduced to the rest level. The photons increased at the 0th hour after exercise compared to that of the normoxic control (P 0.99). Conclusions Exercise induced the distribution of HIF-1α in the small intestine. The expression of HIF-1α is shown in a time-dependent manner after exercise.