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


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.

SUBMITTER: Koh JH 

PROVIDER: S-EPMC9050893 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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

Koh Jin-Ho JH   Pataky Mark W MW   Dasari Surendra S   Klaus Katherine A KA   Vuckovic Ivan I   Ruegsegger Gregory N GN   Kumar Arathi Prabha AP   Robinson Matthew M MM   Nair K Sreekumaran KS  

Nature communications 20220428 1


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 expressio  ...[more]

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