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
© 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
Publication in research information system
MetadataShow full item record
Related funder(s)Academy of Finland
Funding program(s)Academy Project, AoF; Research post as Academy Research Fellow, 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.
Showing items with similar title or keywords.
The metabolic responses to electrical pulse-induced contractions in C2C12 myotubes are greater in high glucose medium Mäntyselkä, Sakari (2021)Osaa liikunnan terveyshyötyjen mekanismeista on vaikeaa tutkia ihmisillä tai koe-eläimillä. Viljeltyjen C2C12 myotuubien sähköpulssistimulaatiolla (EPS, engl. electrical pulse stimulation) voidaan mallintaa lihassupistuksia ...
Peräkylä, Juuli (2020)Säännöllisellä liikunnalla on positiivinen vaikutus kokonaisvaltaiseen terveyteen muun muassa parantuneen aerobisen metabolian kautta. Lihassolujen (myotuubien) sähköpulssistimulaatio (engl. electrical pulse stimulation; ...
Karvinen, Sira; Fachada, Vasco; Sahinaho, Ulla-Maria; Pekkala, Satu; Lautaoja, Juulia H.; Mäntyselkä, Sakari; Permi, Perttu; Hulmi, Juha J.; Silvennoinen, Mika; Kainulainen, Heikki (MDPI AG, 2022)Impaired lipid metabolism is a common risk factor underlying several metabolic diseases such as metabolic syndrome and type 2 diabetes. Branched-chain amino acids (BCAAs) that include valine, leucine and isoleucine have ...
Interactive effects of aging and aerobic capacity on energy metabolism–related metabolites of serum, skeletal muscle, and white adipose tissue Zhuang, Haihui; Karvinen, Sira; Törmäkangas, Timo; Zhang, Xiaobo; Ojanen, Xiaowei; Velagapudi, Vidya; Alen, Markku; Britton, Steven L.; Koch, Lauren G.; Kainulainen, Heikki; Cheng, Sulin; Wiklund, Petri (Springer, 2021)Aerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, ...
Lehtonen, Elias (2019)Johdanto. Haaraketjuiset aminohapot (HKAH, leusiini, isoleusiini, valiini) ja niiden aineenvaihdunta on liitetty parempaan aineenvaihdunnalliseen terveyteen, pidempään elinkaareen, parantuneeseen glukoosi- ja rasva-ainee ...