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Havers, T.* ; Eggelbusch, M.* ; Meinhold, M.* ; Sing, K.* ; Okrojek, R.* ; Artati, A. ; Witting, M. ; Lutter, D. ; Kieker, C.V.* ; Starke, C.* ; More, T.* ; Hiller, K.* ; Dela, F.* ; Schönfelder, M.* ; Kafka, A.* ; Geisler, S.* ; Wackerhage, H.*

Divergent skeletal muscle metabolite exchange in insulin-like growth factor-1-stimulated myotubes and resistance-exercised human muscle.

Exp. Physiol., DOI: 10.1113/EP094096 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Skeletal muscle hypertrophy requires a substantial nutrient influx for biomass accretion, but global metabolite exchange during growth is poorly characterized. Therefore, we profiled the metabolite uptake and release in insulin-like growth factor-1 (IGF-1)-stimulated C2C12 myotubes and human muscle 24 h after resistance exercise. Differentiated C2C12 myotubes were stimulated to grow with IGF-1 (100 ng/mL, 24 h) or received vehicle control. To measure metabolite exchange, we analysed fresh and spent media by gas chromatography-mass spectroscopy metabolomics. In a second experiment, seven untrained adults (three males and four females; age 25.6 ± 3.2 years; body mass index 23.8 ± 2.8 kg/m2) performed single-leg hypertrophy-oriented resistance exercise, with the contralateral leg serving as the control. After 24 h, we obtained arteriovenous blood samples in the postabsorptive state and analysed plasma by untargeted liquid chromatography-mass spectroscopy metabolomics, characterizing the directionality of metabolite exchange across the human leg. In vitro, IGF-1 increased uptake of serine, arginine and pyridoxamine, while enhancing lactate release (all P < 0.05), reflecting anabolic, Warburg-like reprogramming. In vivo, 24 h postexercise there were modest global shifts (principal components analysis: PC1 8.8%, PC2 6.3% variance) and no significant essential amino acid uptake. Nominal differences (P < 0.05) included increased uptake of peptide-related metabolites (acisoga and 2-amino-4-CP) and α-ketoglutarate, alongside release of C12:0 and C16:0 acylcarnitines. No in vivo differences persisted after false discovery rate correction. Although IGF-1 stimulation in vitro promotes coordinated nitrogen-rich metabolite uptake and lactate release, human muscle 24 h postexercise in a postabsorptive state is characterized by increased peptide turnover and lipid release rather than net amino acid uptake. This indicates limited substrate accumulation and net biomass accretion in the absence of exogenous nutrients.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter C2c12 Myotubes ; Warburg‐like Metabolism ; Anabolic Reprogramming ; Arteriovenous Metabolomics ; Skeletal Muscle Hypertrophy
ISSN (print) / ISBN 0958-0670
e-ISSN 1469-445X
Zeitschrift Experimental Physiology
Verlag Wiley
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
Institute of Diabetes and Obesity (IDO)