Resistance training relieves skeletal muscle atrophy induced by hypoxia via the Akt- FoxO1-MuRF1/Atrogin-1 signaling pathway

Purpose: This study investigated the effects of resistance training at continuous hypoxia in rat skeletal muscles, with a focus on the modulation of Forkhead box protein O1 (FoxO1) signaling by protein kinase B (PKB/Akt) in this process. Methods: In an intervention experiment, male Sprague-Dawley rats were exposed to simulated hypoxia and subjected to resistance training for four weeks. The biceps of forelimb and extensor digitorum longus (EDL) muscle were isolated for histological observation and biochemical analysis. L6 rat myoblasts were differentiated into myotubes in the cell culture experiment and then subjected to hypoxic conditions with the addition of an Akt activator. The cells were harvested to observe their morphology and determine the expression level of FoxO1 and downstream signaling molecules. Results: Morphological observation showed the wet weight of the EDL and biceps of the upper limb was significantly higher in the hypoxia-training (HR) group than in the hypoxia (H) group ( P < 0.05 and P < 0.05). Resistance training significantly enhanced Akt expression and FoxO1 phosphorylation ( P < 0.01 and P < 0.05) in skeletal muscle. In myotubes activated Akt under 1% O2 conditions, FoxO1 phosphorylation at S256 was up-regulated, while expression of MuRF1 and Atrogin-1 was reduced ( P < 0.05 and P < 0.05). Conclusion: Resistance training alleviated skeletal muscle atrophy induced by hypoxia, in which FoxO1 phosphorylated by Akt at the S256 position and down-regulation of E3 ligase MuRF-1 and Atrogin-1 in skeletal muscle.