Exercise induces tissue hypoxia and HIF-1α redistribution in the small intestine

Background:Exercise induces blood flow redistribution among tissues,leading to splanchnic hypoperfusion.Intestinal epithelial cells are positioned between the anaerobic lumen and the highly metabolic lamina propria with an oxygen gradient.Hypoxia-inducible factor(HIF)-la is pivotal in the transcriptional response to the oxygen flux.Methods:In this study,the pimonidazole hydrochloride staining was applied to observe the tissue hypoxia in different organs,which might be affected by the blood flow redistribution.The HIF-la luciferase reporter ROSA26 oxygen-dependent degradation domain(ODD)-Luc/^+mouse model(ODD domain-Luc;female,n=3-6/group) was used to detect the HIF-la expression in the intestine.We used 3 swimming models:moderate exercise for 30 min,heavy-intensity exercise bearing 5% bodyweight for 1.5 h,and long-time exercise for 3 h.Results:We found that 1 session of swimming at different intensities could induce tissue hypoxia redistribution in the small intestine,colon,liver and kidney,but not in the spleen,heart,and skeletal muscle.Our data showed that exercise exacerbated the extent of physiological hypoxia in the small intestine.Next,using ODD-Luc mice,we found that moderate exercise increased the in vivo HIF-1α level in the small intestine.The postexercise HIF-1α level was gradually decreased in a time-dependent manner.Interestingly,the redistribution of tissue hypoxia and the increase of HIF-la expression were not related to the exercise intensity and duration.Conclusion:This study provided evidence that the small intestine is the primary target organ for exercise-induced tissue hypoxia and HIF-la redistribution,suggesting that HIF-1α may be a potential target for the regulation of gastrointestinal functions after exercise.

Background'. Exercise induces blood flow redistribution among tissues, leading to splanchnic hypoperfusion. Intestinal epithelial cells are positionedbetween the anaerobic lumen and the highly metabolic lamina propria with an oxygen gradient. Hypoxia-inducible factor (HIF)-la is piv・otal in the transcriptional response to the oxygen flux.Methods: In this study, the pimonidazole hydrochloride staining was applied to observe the tissue hypoxia in different organs, which might beaffected by the blood flow redistribution. The HIF-la luciferase reporter ROSA26 oxygen-dependent degradation domain (ODD)-Luc/+ mousemodel (ODD domain-Luc;female, n = 3—6/group) was used to detect the HIF-la expression in the intestine. We used 3 swimming models: mod・erate exercise for 30 min, heavy-intensity exercise bearing 5% bodyweight for 1.5 h, and long-time exercise for 3 h.Results'. We found that 1 session of swimming at different intensities could induce tissue hypoxia redistribution in the small intestine, colon, liverand kidney, but not in the spleen, heart, and skeletal muscle. Our data showed that exercise exacerbated the extent of physiological hypoxia in thesmall intestine. Next, using ODD-Luc mice, we found that moderate exercise increased the in vivo HIF-la level in the small intestine. The post・exercise HIF-la level was gradually decreased in a time-dependent manner. Interestingly, the redistribution of tissue hypoxia and the increase ofHIF-la expression were not related to the exercise intensity and duration.Conclusion'. This study provided evidence that the small intestine is the primary target organ for exercise-induced tissue hypoxia and HIF-laredistribution, suggesting that HIF-la may be a potential target for the regulation of gastrointestinal functions after exercise.