Higher glucose availability augments the metabolic responses of the C2C12 myotubes to exercise-like electrical pulse stimulation
dc.contributor.author | Lautaoja, Juulia H. | |
dc.contributor.author | O'Connell, Thomas M. | |
dc.contributor.author | Mäntyselkä, Sakari | |
dc.contributor.author | Peräkylä, Juuli | |
dc.contributor.author | Kainulainen, Heikki | |
dc.contributor.author | Pekkala, Satu | |
dc.contributor.author | Permi, Perttu | |
dc.contributor.author | Hulmi, Juha J. | |
dc.contributor.department | Otolaryngology -- Head and Neck Surgery, School of Medicine | |
dc.date.accessioned | 2023-08-11T17:17:37Z | |
dc.date.available | 2023-08-11T17:17:37Z | |
dc.date.issued | 2021 | |
dc.description.abstract | The application of exercise-like electrical pulse simulation (EL-EPS) has become a widely used exercise mimetic in vitro. EL-EPS produces similar physiological responses as in vivo exercise, while less is known about the detailed metabolic effects. Routinely, the C2C12 myotubes are cultured in high-glucose medium (4.5 g/L), which may alter EL-EPS responses. In this study, we evaluate the metabolic effects of EL-EPS under the high- and low-glucose (1.0 g/L) conditions to understand how substrate availability affects the myotube response to EL-EPS. The C2C12 myotube, media, and cell-free media metabolites were analyzed using untargeted nuclear magnetic resonance (NMR)-based metabolomics. Furthermore, translational and metabolic changes and possible exerkine effects were analyzed. EL-EPS enhanced substrate utilization as well as production and secretion of lactate, acetate, 3-hydroxybutyrate, and branched-chain fatty acids (BCFAs). The increase in BCFAs correlated with branched-chain amino acids (BCAAs) and BCFAs were strongly decreased when myotubes were cultured without BCAAs suggesting the action of acyl-CoA thioesterases on BCAA catabolites. Notably, not all EL-EPS responses were augmented by high glucose because EL-EPS increased phosphorylated c-Jun N-terminal kinase and interleukin-6 secretion independent of glucose availability. Administration of acetate and EL-EPS conditioned media on HepG2 hepatocytes had no adverse effects on lipolysis or triacylglycerol content. Our results demonstrate that unlike in cell-free media, the C2C12 myotube and media metabolites were affected by EL-EPS, particularly under high-glucose condition suggesting that media composition should be considered in future EL-EPS studies. Furthermore, acetate and BCFAs were identified as putative exerkines warranting more research. NEW & NOTEWORTHY: The present study examined for the first time the metabolome of 1) C2C12 myotubes, 2) their growth media, and 3) cell-free media after exercise-like electrical pulse stimulation under distinct nutritional loads. We report that myotubes grown under high-glucose conditions had greater responsiveness to EL-EPS when compared with lower glucose availability conditions and increased media content of acetate and branched-chain fatty acids suggests they might act as putative exerkines warranting further research. | |
dc.identifier.citation | Lautaoja JH, M O'Connell T, Mäntyselkä S, et al. Higher glucose availability augments the metabolic responses of the C2C12 myotubes to exercise-like electrical pulse stimulation. Am J Physiol Endocrinol Metab. 2021;321(2):E229-E245. doi:10.1152/ajpendo.00133.2021 | |
dc.identifier.uri | https://hdl.handle.net/1805/34860 | |
dc.language.iso | en_US | |
dc.publisher | American Physiological Society | |
dc.relation.isversionof | 10.1152/ajpendo.00133.2021 | |
dc.relation.journal | American Journal of Physiology: Endocrinology and Metabolism | |
dc.rights | Publisher Policy | |
dc.source | PMC | |
dc.subject | Acetate | |
dc.subject | Branched-chain fatty acids | |
dc.subject | Exerkine | |
dc.subject | Metabolomics | |
dc.subject | Skeletal muscle | |
dc.title | Higher glucose availability augments the metabolic responses of the C2C12 myotubes to exercise-like electrical pulse stimulation | |
dc.type | Article | |
ul.alternative.fulltext | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410101/ |
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