Metabolomic analysis of primary human skeletal muscle cells during myogenic progression

Abstract

Abstract Skeletal muscle constitutes more than 30% of total body mass using substrates such as glycogen, glucose, free fatty acids, and creatinine phosphate to generate energy. Consequently, multinucleated myofibers and resident mononucleated stem cells (satellite cells) generate several metabolites, which enter into circulation affecting the function of other organs, especially during exercise and atrophy. The present study was aimed at building a comprehensive profile of metabolites in primary human skeletal muscle cells during myogenic progression in an untargeted metabolomics approach using a high resolution Orbitrap Fusion Tribrid Mass Spectrometer. Identification of metabolites with multivariate statistical analyses showed a global shift in metabolomic profiles between myoblasts undergoing proliferation and differentiation along with distinctly separable profiles between early and late differentiating cultures. Pathway analyses of 71 unique metabolites revealed that Pantothenate metabolism and Coenzyme A biosynthesis and Arginine Proline metabolism play dominant roles in proliferating myoblasts, while metabolites involved in vitamin B6, Glyoxylate and Dicarboxylate, Nitrogen, Glutathione, and Tryptophan metabolism were upregulated during differentiation. We found that early and late differentiating cultures displayed differences in Phenylalanine, Tyrosine, Glycine, Serine and Threonine metabolism. Our results identify metabolites during maturation of muscle from progenitor myoblasts that have implications in muscle regeneration and pathophysiology.