Higher glucose availability augments the metabolic responses of the C2C12 myotubes to exercise-like electrical pulse stimulation
Lautaoja, J. H., O'Connell, T., Mäntyselkä, S., Peräkylä, J., Kainulainen, H., Pekkala, S., Permi, P., & Hulmi, J. J. (2021). Higher glucose availability augments the metabolic responses of the C2C12 myotubes to exercise-like electrical pulse stimulation. American Journal of Physiology : Endocrinology and Metabolism, 321(2), E229-E245. https://doi.org/10.1152/ajpendo.00133.2021
DisciplineLiikuntalääketiedeLiikuntafysiologiaNanoscience CenterSports and Exercise MedicineExercise PhysiologyNanoscience Center
Embargoed until: 2022-06-28Request copy from author
© 2021, American Journal of Physiology-Endocrinology and Metabolism
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. Further, 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. Further, acetate and BCFAs were identified as putative exerkines warranting more research. ...
PublisherAmerican Physiological Society
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Related funder(s)Academy of Finland
Funding program(s)Research post as Academy Research Fellow, AoF; Academy Project, AoF
Additional information about fundingThis work was funded by the Academy of Finland (Grant No. 298875 to H.K, 308042 to S.P., 323435 to P.P and 275922 to J.J.H.). T.M.O. is supported by grants from National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases (P01AG039355 and P30AR072581) as well as the Additional Ventures, Single Ventricle Research Fund.
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