Metabolic Reprogramming of Hypertrophying Skeletal Muscle Cells
Dokumenttyp:
Konferenzbeitrag
Art des Konferenzbeitrags:
Vortrag / Präsentation
Autor(en):
Philipp Baumert, Karin Kleigrewe, Chen Meng, Martin Schönfelder, Henning Wackerhage
Abstract:
Introduction
Resistance training is an effective intervention to increase muscle mass and function in athletes and patients (Colberg et al., 2016). Whilst we know much about how resistancetraining increases skeletal muscle mass, we poorly understand the underlying mechanism of metabolic adaptations when muscle hypertrophies. The aim of this study was therefore to investigate the effect of insulin-like growth factor (Igf)-1-stimulated C2C12 myotube hypertrophy on the muscle metabolome.
Methods
C2C12 cells were cultured and differentiated to myotubes using standard tissue culture techniques (Watt et al., 2010). Three days after initiation of differentiation, cells were treated with vehicle (control; VC), Igf-1 (100 ng/mL; IGF) or Rapamycin (10 ng/mL; RAP) for 48 h. Metabolites were extracted in 80% methanol and then analysed with liquid chromatography-tandem mass spectrometry. Data were analysed using a Student’s t-test for metabolite concentration. A false discovery rate (FDR) of < 0.2 was used to correct for multiple testing.
Results
Muscle growth stimulation increased lactic acid production in IGF compared to VC (198-306%; FDR = 0.09) and RAP (608-1,222%; FDR = 0.04). IGF increased concentrations of pentose phosphate pathway metabolites (e. g. Ribose 5-phosphate) as well as 13 amino acids (AA) when compared to VC and RAP (all FDR < 0.2), respectively.
Discussion
Our data suggest that Igf-1-stimulated C2C12 myotube hypertrophy is associated with increased glycolytic and pentose phosphate pathway flux. An increased rate of aerobic glycolysis is a sign for the Warburg effect by which healthy and cancerous, proliferating cells reprogram their metabolism to generate substrates for anabolic reactions. The results here suggest that a similar metabolic reprogramming also occurs during muscle hypertrophy.