Exercise preconditioning diminishes skeletal muscle atrophy after hindlimb suspension in mice

Abstract

The aim of the present study was to investigate whether short-term, concurrent exercise training before hindlimb suspension (HLS) prevents or diminishes both soleus and gastrocnemius atrophy and to analyze whether changes in mitochondrial molecular markers were associated. Male C57BL/6 mice were assigned to control at 13 ± 1 wk of age, 7-day HLS at 12 ± 1 wk of age (HLS), 2 wk of exercise training before 7-day HLS at 10 ± 1 wk of age (Ex+HLS), and 2 wk of exercise training at 11 ± 1 wk of age (Ex) groups. HLS resulted in a 27.1% and 21.5% decrease in soleus and gastrocnemius muscle weight-to-body weight ratio, respectively. Exercise training before HLS resulted in a 5.6% and 8.1% decrease in soleus and gastrocnemius weight-to-body weight ratio, respectively. Exercise increased mitochondrial biogenesis- and function-associated markers and slow myosin heavy chain (SMHC) expression, and reduced fiber-type transitioning marker myosin heavy chain 4 (Myh4). Ex+HLS revealed decreased reactive oxygen species (ROS) and oxidative stress compared with HLS. Our data indicated the time before an atrophic setting, particularly caused by muscle unloading, may be a useful period to intervene short-term, progressive exercise training to prevent skeletal muscle atrophy and is associated with mitochondrial biogenesis, function, and redox balance.NEW & NOTEWORTHY Mitochondrial dysfunction is associated with disuse-induced skeletal muscle atrophy, whereas exercise is known to increase mitochondrial biogenesis and function. Here we provide evidence of short-term concurrent exercise training before an atrophic event protecting skeletal muscle from atrophy in two separate muscles with different, dominant fiber-types, and we reveal an association with the adaptive changes of mitochondrial molecular markers to exercise.

Doxorubicin‐induced skeletal muscle atrophy: Elucidating the underlying molecular pathways

“…When comparing the results of this meta‐analysis to other models of skeletal muscle atrophy, we found that a 7‐day hind limb suspension resulted in a comparable decrease in soleus (27.1%) and gastrocnemius muscle (21.5%) weight to body weight ratio in wildtype mice . Moreover, evidence shows that the network of interacting signalling pathways that we found to be involved in doxorubicin‐induced skeletal muscle atrophy, also share common pathways with disuse atrophy .…”

Muscle unloading: A comparison between spaceflight and ground‐based models

“…Muscle mass is determined by the balance between muscle protein synthesis and degradation which control the accretion or loss of muscle mass (Figure ) . The primary mechanism for disuse atrophy seems to be the reduction in muscle protein synthesis in mice, rats and humans . Muscle protein synthesis is stimulated by the activation of mammalian target of rapamycin (mTOR) pathway, a key regulator of translation initiation and its downstream targets S6 kinase‐1 (S6K1) and 4E binding protein 1 (4E‐BP1).…”

Ischemic Preconditioning in Cardiac and Skeletal Muscle Induced by Exercise

“…The mechanisms involved in the production of the beneficial effects of preconditioning in skeletal muscle are not yet clear, although it has recently been shown to decrease skeletal muscle atrophy induced by the discharge of the hind limbs (HU) and the mechanism that can participate it is through HDAC4/Gadd45α [23]. Although, interestingly, the mechanisms of physical training to reduce muscle atrophy are associated with the biogenesis, function and redox balance of mitochondria, the same mechanism involved in preconditioning [24]. The redox mechanism seems to be common in preconditioning processes regardless of white tissue, probably not the only shared mechanism, but certainly unlike the cardiac muscle, in skeletal muscle hypertrophy represents a greater capacity for energy regulation.…”