PKM2 Determines Myofiber Hypertrophy In Vitro and Increases in Response to Resistance Exercise in Human Skeletal Muscle

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PKM2 Determines Myofiber Hypertrophy In Vitro and Increases in Response to Resistance Exercise in Human Skeletal Muscle. / Verbrugge, Sander A J; Gehlert, Sebastian; Stadhouders, Lian E M et al.

In: International journal of molecular sciences, Vol. 21, No. 19, 25.09.2020, p. 1-15.

Publications: Contribution to journalJournal articlesResearchpeer-review

Harvard

Verbrugge, SAJ, Gehlert, S, Stadhouders, LEM, Jacko, D, Aussieker, T, M J de Wit, G, Vogel, ISP, Offringa, C, Schönfelder, M, Jaspers, RT & Wackerhage, H 2020, 'PKM2 Determines Myofiber Hypertrophy In Vitro and Increases in Response to Resistance Exercise in Human Skeletal Muscle', International journal of molecular sciences, vol. 21, no. 19, pp. 1-15. https://doi.org/10.3390/ijms21197062, https://doi.org/10.3390/ijms21197062

APA

Verbrugge, S. A. J., Gehlert, S., Stadhouders, L. E. M., Jacko, D., Aussieker, T., M J de Wit, G., Vogel, I. S. P., Offringa, C., Schönfelder, M., Jaspers, R. T., & Wackerhage, H. (2020). PKM2 Determines Myofiber Hypertrophy In Vitro and Increases in Response to Resistance Exercise in Human Skeletal Muscle. International journal of molecular sciences, 21(19), 1-15. https://doi.org/10.3390/ijms21197062, https://doi.org/10.3390/ijms21197062

Vancouver

Bibtex

@article{571918af8311488cb6b0b1151a2b57dd,
title = "PKM2 Determines Myofiber Hypertrophy In Vitro and Increases in Response to Resistance Exercise in Human Skeletal Muscle",
abstract = "Nearly 100 years ago, Otto Warburg investigated the metabolism of growing tissues and discovered that tumors reprogram their metabolism. It is poorly understood whether and how hypertrophying muscle, another growing tissue, reprograms its metabolism too. Here, we studied pyruvate kinase muscle (PKM), which can be spliced into two isoforms (PKM1, PKM2). This is of interest, because PKM2 redirects glycolytic flux towards biosynthetic pathways, which might contribute to muscle hypertrophy too. We first investigated whether resistance exercise changes PKM isoform expression in growing human skeletal muscle and found that PKM2 abundance increases after six weeks of resistance training, whereas PKM1 decreases. Second, we determined that Pkm2 expression is higher in fast compared to slow fiber types in rat skeletal muscle. Third, by inducing hypertrophy in differentiated C2C12 cells and by selectively silencing Pkm1 and/or Pkm2 with siRNA, we found that PKM2 limits myotube growth. We conclude that PKM2 contributes to hypertrophy in C2C12 myotubes and indicates a changed metabolic environment within hypertrophying human skeletal muscle fibers. PKM2 is preferentially expressed in fast muscle fibers and may partly contribute to the increased potential for hypertrophy in fast fibers.",
keywords = "Cancer, Glycolysis, Hypertrophy, Insulin-like growth factor 1, Metabolic reprogramming, Pyruvate kinase, Resistance exercise, Skeletal muscle, Warburg effect",
author = "Verbrugge, {Sander A J} and Sebastian Gehlert and Stadhouders, {Lian E M} and Daniel Jacko and Thorben Aussieker and {M J de Wit}, Gerard and Vogel, {Ilse S P} and Carla Offringa and Martin Sch{\"o}nfelder and Jaspers, {Richard T} and Henning Wackerhage",
year = "2020",
month = sep,
day = "25",
doi = "10.3390/ijms21197062",
language = "English",
volume = "21",
pages = "1--15",
journal = "International journal of molecular sciences",
issn = "1422-0067",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "19",

}

RIS

TY - JOUR

T1 - PKM2 Determines Myofiber Hypertrophy In Vitro and Increases in Response to Resistance Exercise in Human Skeletal Muscle

AU - Verbrugge, Sander A J

AU - Gehlert, Sebastian

AU - Stadhouders, Lian E M

AU - Jacko, Daniel

AU - Aussieker, Thorben

AU - M J de Wit, Gerard

AU - Vogel, Ilse S P

AU - Offringa, Carla

AU - Schönfelder, Martin

AU - Jaspers, Richard T

AU - Wackerhage, Henning

PY - 2020/9/25

Y1 - 2020/9/25

N2 - Nearly 100 years ago, Otto Warburg investigated the metabolism of growing tissues and discovered that tumors reprogram their metabolism. It is poorly understood whether and how hypertrophying muscle, another growing tissue, reprograms its metabolism too. Here, we studied pyruvate kinase muscle (PKM), which can be spliced into two isoforms (PKM1, PKM2). This is of interest, because PKM2 redirects glycolytic flux towards biosynthetic pathways, which might contribute to muscle hypertrophy too. We first investigated whether resistance exercise changes PKM isoform expression in growing human skeletal muscle and found that PKM2 abundance increases after six weeks of resistance training, whereas PKM1 decreases. Second, we determined that Pkm2 expression is higher in fast compared to slow fiber types in rat skeletal muscle. Third, by inducing hypertrophy in differentiated C2C12 cells and by selectively silencing Pkm1 and/or Pkm2 with siRNA, we found that PKM2 limits myotube growth. We conclude that PKM2 contributes to hypertrophy in C2C12 myotubes and indicates a changed metabolic environment within hypertrophying human skeletal muscle fibers. PKM2 is preferentially expressed in fast muscle fibers and may partly contribute to the increased potential for hypertrophy in fast fibers.

AB - Nearly 100 years ago, Otto Warburg investigated the metabolism of growing tissues and discovered that tumors reprogram their metabolism. It is poorly understood whether and how hypertrophying muscle, another growing tissue, reprograms its metabolism too. Here, we studied pyruvate kinase muscle (PKM), which can be spliced into two isoforms (PKM1, PKM2). This is of interest, because PKM2 redirects glycolytic flux towards biosynthetic pathways, which might contribute to muscle hypertrophy too. We first investigated whether resistance exercise changes PKM isoform expression in growing human skeletal muscle and found that PKM2 abundance increases after six weeks of resistance training, whereas PKM1 decreases. Second, we determined that Pkm2 expression is higher in fast compared to slow fiber types in rat skeletal muscle. Third, by inducing hypertrophy in differentiated C2C12 cells and by selectively silencing Pkm1 and/or Pkm2 with siRNA, we found that PKM2 limits myotube growth. We conclude that PKM2 contributes to hypertrophy in C2C12 myotubes and indicates a changed metabolic environment within hypertrophying human skeletal muscle fibers. PKM2 is preferentially expressed in fast muscle fibers and may partly contribute to the increased potential for hypertrophy in fast fibers.

KW - Cancer

KW - Glycolysis

KW - Hypertrophy

KW - Insulin-like growth factor 1

KW - Metabolic reprogramming

KW - Pyruvate kinase

KW - Resistance exercise

KW - Skeletal muscle

KW - Warburg effect

UR - https://www.mendeley.com/catalogue/98ca7d31-3c8c-3dbd-b822-1ab41febfcdf/

U2 - 10.3390/ijms21197062

DO - 10.3390/ijms21197062

M3 - Journal articles

C2 - 32992783

VL - 21

SP - 1

EP - 15

JO - International journal of molecular sciences

JF - International journal of molecular sciences

SN - 1422-0067

IS - 19

ER -

ID: 5482561