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

• Published in: International journal of molecular sciences 2020-10, Vol.21 (19), p.7062
• Main Authors: Verbrugge, Sander A J, Gehlert, Sebastian, Stadhouders, Lian E M, Jacko, Daniel, Aussieker, Thorben, M J de Wit, Gerard, Vogel, Ilse S P, Offringa, Carla, Schönfelder, Martin, Jaspers, Richard T, Wackerhage, Henning
• Format: Article
• Language: English
• Subjects: Adult; Amino acids; Cancer; Carrier Proteins - metabolism; Cell differentiation; Cell Line; Diabetes; Enzymes; Glycolysis; Health aspects; Humans; Hypertrophy; Isoforms; Kinases; Male; Membrane Proteins - metabolism; Metabolism; Muscle Fibers, Fast-Twitch - enzymology; Muscle Fibers, Fast-Twitch - pathology; Muscle Fibers, Slow-Twitch - enzymology; Muscle Fibers, Slow-Twitch - pathology; Muscles; Musculoskeletal system; Myotubes; Physiological aspects; Protein synthesis; Proteins; Pyruvate kinase; Pyruvic acid; Resistance Training; siRNA; Skeletal muscle; Strength training; Thyroid Hormone-Binding Proteins; Thyroid Hormones - metabolism; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21197062

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 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 and/or 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.