Enhancement of anaerobic glycolysis – a role of PGC-1α4 in resistance exercise

Jin-Ho Koh, Mark W. Pataky, Surendra Dasari, Katherine A. Klaus, Ivan Vuckovic, Gregory N. Ruegsegger, Arathi Prabha Kumar, Matthew M. Robinson and K. Sreekumaran Nair ()
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Jin-Ho Koh: Mayo Clinic
Mark W. Pataky: Mayo Clinic
Surendra Dasari: Mayo Clinic
Katherine A. Klaus: Mayo Clinic
Ivan Vuckovic: Mayo Clinic
Gregory N. Ruegsegger: Mayo Clinic
Arathi Prabha Kumar: Mayo Clinic
Matthew M. Robinson: Oregon State University
K. Sreekumaran Nair: Mayo Clinic

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-30056-6

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