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

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.

Automated summary

There are metabolic differences between growing and non-growing tissues, and hypertrophying muscle reprograms its metabolism similar to cancer cells. Increased glucose uptake in hypertrophying muscle may explain the negative association with type 2 diabetes mellitus and obesity.