Does a Hypertrophying Muscle Fibre Reprogramme its Metabolism Similar to a Cancer Cell?

Authors

• Henning Wackerhage, Technical University of Munich
• Ivan J. Vechetti, University of Nebraska-Lincoln
• Philipp Baumert, Technical University of Munich
• Sebastian Gehlert, University of Hildesheim
• Lore Becker, German Research Center for Environmental Health
• Richard T. Jaspers, Vrije Universiteit Amsterdam
• Martin Hrabě de Angelis, German Research Center for Environmental Health, German Center for Diabetes Research, Technische Universität München

Document Type

Article

Date of this Version

4-23-2022

Citation

Sports Medicine (2022) 52:2569–2578 https://doi.org/10.1007/s40279-022-01676-1

Comments

Open Access

Abstract

In 1924, Otto Warburg asked “How does the metabolism of a growing tissue differ from that of a non-growing tissue?” Currently, we know that proliferating healthy and cancer cells reprogramme their metabolism. This typically includes increased glucose uptake, glycolytic flux and lactate synthesis. A key function of this reprogramming is to channel glycolytic intermediates and other metabolites into anabolic reactions such as nucleotide-RNA/DNA synthesis, amino acid-protein synthesis and the synthesis of, for example, acetyl and methyl groups for epigenetic modification. In this review, we discuss evidence that a hypertrophying muscle similarly takes up more glucose and reprogrammes its metabolism to channel energy metabolites into anabolic pathways. We specifically discuss the functions of the cancer-associated enzymes phosphoglycerate dehydrogenase and pyruvate kinase muscle 2 in skeletal muscle. In addition, we ask whether increased glucose uptake by a hypertrophying muscle explains why muscularity is often negatively associated with type 2 diabetes mellitus and obesity.