PGC-1α and exercise intensity dependent adaptations in mouse skeletal muscle

Area of Science:

• Exercise Physiology
• Molecular Biology
• Skeletal Muscle Metabolism

Background:

• Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a key regulator of mitochondrial biogenesis and exercise adaptation.
• Autophagy plays a role in cellular adaptation to stress, including exercise.

Purpose of the Study:

• To investigate the role of PGC-1α in exercise intensity-dependent and exercise training-induced autophagy in mouse skeletal muscle.
• To determine if PGC-1α is essential for acute exercise and exercise training-induced changes in autophagy markers.

Main Methods:

• Whole-body PGC-1α knockout (KO) and wildtype (WT) mice underwent acute treadmill exercise at low (LI) or moderate (MI) intensity.
• Mice also underwent a 5-week exercise training program (low or moderate intensity).
• Skeletal muscle and blood samples were analyzed for autophagy markers (LC3I, LC3II, p62) and PGC-1α isoform mRNA levels.

Main Results:

• Acute exercise induced intensity-dependent increases in LC3I/II and an intensity-independent decrease in p62 in WT mice, but not in PGC-1α KO mice.
• Exercise training increased LC3II in WT mice independently of intensity and volume, an effect absent in PGC-1α KO mice.
• Exercise-induced PGC-1α isoform mRNA responses were intensity-dependent.

Conclusions:

• Exercise intensity differentially affects skeletal muscle autophagy markers.
• PGC-1α is a critical regulator of both acute exercise and exercise training-induced autophagy in skeletal muscle.
• The regulation of autophagy by PGC-1α may involve specific PGC-1α isoforms.