TitleEnhancement of anaerobic glycolysis - a role of PGC-1α4 in resistance exercise.
Publication TypeJournal Article
Year of Publication2022
AuthorsKoh, J-H, Pataky, MW, Dasari, S, Klaus, KA, Vuckovic, I, Ruegsegger, GN, KUMAR, ARATHIPRABHA, Robinson, MM, K Nair, S
JournalNat Commun
Date Published04/2022
KeywordsAnaerobiosis, Glycolysis, Humans, PPAR-beta, Resistance Training, Transcription Factors

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-1α4 (an isoform of the transcriptional co-activator PGC-1α) expression not only promotes muscle hypertrophy but also enhances glycolysis, providing a rapid supply of ATP for muscle contractions. In human skeletal muscle, PGC-1α4 binds to the nuclear receptor PPARβ following RET, resulting in downstream effects on the expressions of key glycolytic genes. In myotubes, we show that PGC-1α4 overexpression increases anaerobic glycolysis in a PPARβ-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.

Alternate JournalNat Commun
PubMed ID35484130
PubMed Central IDPMC9050893