PGC-1α regulates myonuclear accretion after moderate endurance training

Area of Science:

• Skeletal muscle physiology
• Molecular biology
• Exercise adaptation

Background:

• Skeletal muscle fibres have high transcriptional demands, requiring numerous myonuclei to maintain function.
• Myonuclear domains (MNDs) correlate with fibre size, and endurance training induces adaptive changes like myonuclear accretion.
• Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is implicated in mitochondrial biogenesis and myonuclear accretion, but its necessity in training adaptation was unclear.

Purpose of the Study:

• To investigate the role of PGC-1α in myonuclear accretion and MND organization in response to endurance training.
• To determine if PGC-1α is essential for skeletal muscle adaptation to endurance exercise, particularly concerning fibre size.

Main Methods:

• Comparison of endurance-trained wild-type mice and mice lacking PGC-1α in skeletal muscle (PGC-1α mKO).
• Evaluation of myonuclear distribution, organization, and myonuclear domain (MND) size relative to fibre cross-sectional area (CSA).

Main Results:

• PGC-1α governs myonuclear accretion in an endurance training-dependent and muscle fibre size-dependent manner.
• In larger fibres, PGC-1α is critical for maintaining the relationship between MND size and CSA after training.
• Trained PGC-1α mKO mice showed a negative correlation between nuclear number and CSA, indicating a failure of myonuclear numbers to scale with fibre size.

Conclusions:

• PGC-1α is a key contributor to myonuclear accretion during moderate-intensity endurance training.
• This PGC-1α-mediated accretion supports the adaptive response by facilitating transcription for mitochondrial biogenesis.
• The findings highlight PGC-1α's importance in maintaining transcriptional capacity in skeletal muscle during exercise adaptation.