Enhancement of anaerobic glycolysis - a role of PGC-1 alpha 4 in resistance exercise

Resistance exercise training (RET) is an effective countermeasure to sarcopenia, related frailty and metabolic disorders. Here, the authors show that an RET-induced increase in PGC-1 alpha 4 expression not only promotes muscle hypertrophy but also enhances glycolysis, providing a rapid supply of ATP for muscle contractions. Resistance exercise training (RET) is an effective countermeasure to sarcopenia, related frailty and metabolic disorders. Here, we show that an RET-induced increase in PGC-1 alpha 4 (an isoform of the transcriptional co-activator PGC-1 alpha) expression not only promotes muscle hypertrophy but also enhances glycolysis, providing a rapid supply of ATP for muscle contractions. In human skeletal muscle, PGC-1 alpha 4 binds to the nuclear receptor PPAR beta following RET, resulting in downstream effects on the expressions of key glycolytic genes. In myotubes, we show that PGC-1 alpha 4 overexpression increases anaerobic glycolysis in a PPAR beta-dependent manner and promotes muscle glucose uptake and fat oxidation. In contrast, we found that an acute resistance exercise bout activates glycolysis in an AMPK-dependent manner. These results provide a mechanistic link between RET and improved glucose metabolism, offering an important therapeutic target to counteract aging and inactivity-induced metabolic diseases benefitting those who cannot exercise due to many reasons.