PKM2 determines myofiber hypertrophy in vitro and increases in response to resistance exercise in human skeletal muscle

Sander A.J. Verbrugge, Sebastian Gehlert*, Lian E.M. Stadhouders, Daniel Jacko, Thorben Aussieker, Gerard M.J. de Wit, Ilse S.P. Vogel, Carla Offringa, Martin Schönfelder, Richard T. Jaspers, Henning Wackerhage

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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.

Original languageEnglish
Article number7062
Pages (from-to)1-15
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume21
Issue number19
Early online date25 Sep 2020
DOIs
Publication statusPublished - 1 Oct 2020

Keywords

  • Cancer
  • Glycolysis
  • Hypertrophy
  • Insulin-like growth factor 1
  • Metabolic reprogramming
  • Pyruvate kinase
  • Resistance exercise
  • Skeletal muscle
  • Warburg effect

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