TY - JOUR
T1 - Enhancement of anaerobic glycolysis – a role of PGC-1α4 in resistance exercise
AU - Koh, Jin Ho
AU - Pataky, Mark W.
AU - Dasari, Surendra
AU - Klaus, Katherine A.
AU - Vuckovic, Ivan
AU - Ruegsegger, Gregory N.
AU - Kumar, Arathi Prabha
AU - Robinson, Matthew M.
AU - Nair, K. Sreekumaran
N1 - Funding Information:
Grant funding to support this research from the National institutes of Health include R01AG062859 (K.S.N.and UL1 TR000135), and T32 DK007352 (M.W.P.). Funding was also provided through the National Research Foundation of Korea NRF-2019R1A2C1006334 (J.H.K.). Additional support was provided by the Mayo Foundation, and the Dr. Emslander Professorship (K.S.N.). The authors would like to thank the effort and time of the study participants. Additionally, we acknowledge the skilled assistance of Melissa Aakre and the staff of the Clinical Research Unit at Mayo Clinic and Mayo Clinic Metabolomics Core.
Funding Information:
Grant funding to support this research from the National institutes of Health include R01AG062859 (K.S.N.and UL1 TR000135), and T32 DK007352 (M.W.P.). Funding was also provided through the National Research Foundation of Korea NRF-2019R1A2C1006334 (J.H.K.). Additional support was provided by the Mayo Foundation, and the Dr. Emslander Professorship (K.S.N.). The authors would like to thank the effort and time of the study participants. Additionally, we acknowledge the skilled assistance of Melissa Aakre and the staff of the Clinical Research Unit at Mayo Clinic and Mayo Clinic Metabolomics Core.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-30056-6
DO - 10.1038/s41467-022-30056-6
M3 - Article
C2 - 35484130
AN - SCOPUS:85128912839
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2324
ER -