The Mechanism of Exercise Preventing Skeletal Muscle Atrophy

Background Skeletal muscle atrophy is the consequence of protein degradation exceeding protein synthesis. This arises for a multitude of reasons including the unloading of muscle during microgravity, post‐surgery bedrest, immobilization of a limb after injury, and overall disuse of the musculature. Mitochondrial dysfunction is associated with skeletal muscle atrophy and contributes to the induction of protein degradation and cell apoptosis with the loss of organelle function. The development of therapies to enhance mitochondrial function prior to skeletal muscle atrophy settings to diminish protein degradation is scarce. Objective We are investigating whether an exercise treatment prior to an atrophic setting will diminish the skeletal muscle atrophy incurred during hindlimb suspension (HLS) in mice. Methods Male C57BL/6 (wild‐type) mice between 11–14 weeks of age were assigned to control, HLS only (HLS‐only), exercise only (Ex‐only), and exercise prior to HLS (Ex+HLS), groups. The exercise protocol consisted of 14 progressive exercise sessions over an 18‐day period and the HLS protocol lasted 7 consecutive days. At the end of treatments mice were first anesthetized and blood flow imaging of the hindlimb was done using laser Doppler technology. Mice were then sacrificed and the soleus and gastrocnemius muscle were excised and analyzed for muscle weight. Immunohistochemistry staining was done to detect fiber cross‐sectional area. Future measurements will assess concentrations of mitochondrial function proteins in the excised muscle tissue through western blotting techniques. Results HLS‐only resulted in reductions in soleus and gastrocnemius muscle weight of 33.6% and 25.4%, respectively, while exercising prior to HLS led to a decrease in soleus and gastrocnemius weight of 5.1% and 10.8%, respectively, compared to controls. A standardization measurement of soleus muscle weight (mg) to bodyweight (g) ratio decreased 32.7% (.218±.018) in HLS‐only while decreasing 8.1% (.298±.004) in Ex+HLS. Immunostaining revealed greater cross‐sectional area, continuity, and uniformity in Ex+HLS soleus and gastrocnemius muscle fibers compared to HLS‐only. Laser Doppler imaging suggests blood flow in the lower hindlimbs is greater in Ex+HLS mice compared to the HLS only group. Conclusions Data indicates the time before an atrophic setting, particularly caused by muscle unloading and disuse, is a useful period to intervene progressive exercise training to prevent skeletal muscle atrophy which we may be associated with enhanced mitochondrial function. Support or Funding Information NIH Grant HL74185 to SCT