Intermittent reloading attenuates muscle atrophy through modulating Akt/mTOR pathway.

Area of Science:

• Muscle physiology
• Cell signaling
• Biomedical research

Background:

• Hindlimb unloading (HU) induces skeletal muscle atrophy, characterized by reduced muscle mass and fiber size.
• HU disrupts intracellular signaling pathways crucial for muscle maintenance.
• Understanding these molecular changes is vital for developing countermeasures against muscle loss.

Purpose of the Study:

• To investigate the impact of intermittent reloading (IR) on intracellular signaling pathways during hindlimb unloading (HU).
• To determine if IR can attenuate muscle atrophy induced by HU.
• To elucidate the molecular mechanisms underlying IR's effects on skeletal muscle.

Main Methods:

• Male Wistar rats were subjected to 7 days of HU or HU with 4 hours/day of IR.
• The soleus muscle was analyzed for changes in mass, fiber cross-sectional area (CSA), and signaling pathway activation.
• Key signaling molecules (Akt, mTOR), E3 ubiquitin ligases (MAFbx, MuRF1), and nuclear factor kappa B (NFkappaB) activity were assessed.

Main Results:

• HU led to significant muscle fiber atrophy, decreased Akt/mTOR phosphorylation, increased MAFbx/MuRF1 expression, and elevated NFkappaB activity.
• IR treatment attenuated muscle atrophy, partially restored anabolic signaling, normalized MAFbx/MuRF1 expression, and suppressed NFkappaB activity.
• IR effectively counteracted the catabolic effects of HU on skeletal muscle.

Conclusions:

• Intermittent reloading (IR) effectively attenuates skeletal muscle atrophy induced by hindlimb unloading (HU).
• IR's protective effects are mediated by a synergistic action of enhanced anabolic signaling and suppressed catabolic signaling pathways.
• These findings highlight IR as a potential therapeutic strategy for preventing muscle loss in unloading conditions.