A1 Journal article (refereed)
Higher glucose availability augments the metabolic responses of the C2C12 myotubes to exercise-like electrical pulse stimulation (2021)

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

JYU authors or editors

Publication details

All authors or editors: Lautaoja, Juulia H.; O'Connell, Thomas; Mäntyselkä, Sakari; Peräkylä, Juuli; Kainulainen, Heikki; Pekkala, Satu; Permi, Perttu; Hulmi, Juha J.

Journal or series: American Journal of Physiology : Endocrinology and Metabolism

ISSN: 0193-1849

eISSN: 1522-1555

Publication year: 2021

Publication date: 28/06/2021

Volume: 321

Issue number: 2

Pages range: E229-E245

Publisher: American Physiological Society

Publication country: United States

Publication language: English

DOI: https://doi.org/10.1152/ajpendo.00133.2021

Publication open access: Not open

Publication channel open access:

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/77055


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.

Keywords: muscle cells; cell physiology; metabolism; in vitro method; glucose; metabolic products; lactates; acetates; fatty acids

Free keywords: acetate; exerkine; metabolomics; skeletal muscle; branched chain fatty acids

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Ministry reporting: Yes

Reporting Year: 2021

JUFO rating: 2

Last updated on 2023-12-10 at 15:29