HIF-1α Negatively Regulates Irisin Expression Which Involves in Muscle Atrophy Induced by Hypoxia

This is the authors' abstract. We don't add key points for this paper.

Background: Exposure to high altitude environment leads to skeletal muscle atrophy. As a hormone secreted by skeletal muscles after exercise, irisin contributes to promoting muscle regeneration and ameliorating skeletal muscle atrophy, but its role in hypoxia-induced skeletal muscle atrophy is still unclear. Methods & Results: Our results showed that 4 w of hypoxia exposure significantly reduced body weight and gastrocnemius muscle mass of mice, as well as grip strength and the duration time of treadmill exercise. Hypoxia treatment increased HIF-1α expression and decreased both the circulation level of irisin and its precursor protein FNDC5 expression in skeletal muscle. In vitro, CoCl2-induced chemical hypoxia and 1% O2 ambient hypoxia both reduced FNDC5, along with the increase of HIF-1α. Moreover, the decline of area and diameter of myotubes caused by hypoxia were rescued by inhibiting HIF-1α via YC-1. and Conclusions: Collectively, our research indicated that FNDC5/irisin was negatively regulated by HIF-1α and could participate in the regulation of muscle atrophy caused by hypoxia.