Physical inactivity induces the atrophy of skeletal muscle of rats through activating AMPK/FoxO3 signal pathway

OBJECTIVE: Long-term physical inactivity can cause the atrophy of skeletal muscle. The aim of this study is to explore the underlying mechanisms of physical inactivity-induced atrophy of skeletal muscle.

MATERIALS AND METHODS: 14 Sprague- Dawley (SD) male rats were divided into 2 groups including normal control (NC) and hindlimb suspension (HS) groups. After two weeks of HS stimulation, the ratio between skeletal muscle weight and body weight, and cross-sectional area (CSA) of skeletal muscle fibers, were measured. Western blot was applied to evaluate the expression of proteins associated with atrophy and autophagy. The transmission electron microscope was used to observe the ultra-microstructure and the mitochondrial quality of skeletal muscle.

RESULTS: The rats subjected to 2-week HS treatment presented an evident atrophy of the skeletal muscle with a significantly reduced ratio between skeletal muscle weight and body weight, and smaller cross-sectional area (CSA) of skeletal muscle fibers when compared with control rats. Meanwhile, HS stimulation resulted in the damage of mitochondria, the increased expression of MuRF1 and Atrogin-1/MAFbx, and enhanced apoptosis, as well as dysfunctional autophagy in skeletal muscle.

CONCLUSIONS: HS-induced skeletal muscle atrophy involves the activation of AMPK/FoxO3 signal pathway, evidenced as AMPK phosphorylation, FoxO3 activation, and Atrogin-1 and MuRF1 up-regulation. FoxO3-mediated autophagy plays an important regulatory role in HS-induced skeletal muscle atrophy.

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