Hypoxic training upregulates mitochondrial turnover and angiogenesis of skeletal muscle in mice

Abstract

AimsHypoxic training promotes human cardiopulmonary function and exercise performance efficiently, but the myocellular mechanism has been less studied. We aimed to examine the effects of hypoxic trainings on mitochondrial turnover and vascular remodeling of skeletal muscle. Main methodsC57BL/6 J mice were divided into control, hypoxic exposure, exercise training, “live high-train low” (LHTL), and “live low-train high” (LLTH) groups (n = 8/group). Western blot and immunohistochemistry were used to evaluate mitochondrial turnover of gastrocnemius and angiogenesis of quadriceps after six weeks interventions. Key findingsCompared with control group, both LHTL and LLTH increased phosphorylation levels of p38 MAPK markedly (p < 0.05). LLTH also elevated PGC-1α protein expression significantly (p < 0.05). All interventions did not influence Bnip3 and Drp-1 proteins levels (p > 0.05), while LLTH enhanced Parkin and Mff protein contents significantly (p < 0.05). Immunohistochemical analysis showed both LHTL and LLTH promoted CD31 and VEGF expressions (p < 0.05). ATP content, citrate synthase activities of gastrocnemius were robustly elevated in LHTL and LLTH groups (p < 0.01). The exercise training increased Mff protein and ATP content in gastrocnemius as well as VEGF expression in quadriceps (p < 0.05). The hypoxic exposure also increased ATP content, citrate synthase, and ATP synthase activities in gastrocnemius as well as VEGF expression in quadriceps (p < 0.01). SignificanceOur results suggested that hypoxic trainings, especially LLTH, promoted mitochondrial turnover and angiogenesis of skeletal muscle, which may be an underlying mechanism of hypoxic training–induced exercise capacity.