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

Author

Listed:
  • Jin-Ho Koh

    (Mayo Clinic
    Yeungnam University)

  • 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)

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.

Suggested Citation

  • Jin-Ho Koh & Mark W. Pataky & Surendra Dasari & Katherine A. Klaus & Ivan Vuckovic & Gregory N. Ruegsegger & Arathi Prabha Kumar & Matthew M. Robinson & K. Sreekumaran Nair, 2022. "Enhancement of anaerobic glycolysis – a role of PGC-1α4 in resistance exercise," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30056-6
    DOI: 10.1038/s41467-022-30056-6
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    References listed on IDEAS

    as
    1. Nicolas J. Pillon & Brendan M. Gabriel & Lucile Dollet & Jonathon A. B. Smith & Laura Sardón Puig & Javier Botella & David J. Bishop & Anna Krook & Juleen R. Zierath, 2020. "Transcriptomic profiling of skeletal muscle adaptations to exercise and inactivity," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    2. David Amar & Malene E. Lindholm & Jessica Norrbom & Matthew T. Wheeler & Manuel A. Rivas & Euan A. Ashley, 2021. "Time trajectories in the transcriptomic response to exercise - a meta-analysis," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
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