Pgc-1 Alpha Over-Expression Suppresses The Skeletal Muscle Atrophy And Myofiber-Type Composition During Hindlimb Unloading

Disuse leads to severe muscle atrophy and a slow-to-fast myofiber-type transition. PGC-1 (Peroxisome proliferator-activated receptor coactivator 1) is documented to play an important role in muscle atrophy and slow-twitch myofiber determination. Transcription of atrophy-related Atrogin-1 by FoxO3 can be reduced by PGC-1. While Smad3 augments FoxO3-induced Atrogin-1 and MuRF1 promoter activity. So PGC-1, as a transcription co-activator, may regulate hindlimb unloading (HU)-induced myofiber-type transition and muscle atrophy through Smad3. Our results showed that transgenic PGC-1 mice resisted HU-induced muscle loss, atrophy-related genes expression, and slow-to-fast myofiber(-)type transition. Furthermore, over-expression of PGC-1 resisted the increase in pSmad3 during muscle atrophy in vivo and in vitro. And, PGC-1 over-expression inhibited the expression of atrogenes via suppressing the phosphorylation of Smad3 in vitro. Thus, PGC-1 is effective in regulating myofiber-type transition during HU, and it alleviates skeletal muscle atrophy partially through suppressing the activation of Smad3.