Real-time quantification of skeletal muscle metabolism in healthy men using hyperpolarised [1-¹³C]pyruvate reveals training-dependent adaptation
Abstract Skeletal muscle undergoes rapid and dynamic changes in energy demand during exercise, limiting the physiological relevance of resting-state measurements. Here, we demonstrate the feasibility of combining hyperpolarised ¹³C magnetic resonance spectroscopy (¹³C-MRS) with ³¹P-MRS to non-invasively measure real-time metabolic responses in exercising human skeletal muscle. Sedentary and endurance-trained men perform plantar-flexion exercise inside a magnetic resonance scanner. Dynamic hyperpolarised [1-¹³C]pyruvate spectra from the medial gastrocnemius show that increasing exercise intensity escalates pyruvate-to-lactate conversion relative to mitochondrial pyruvate utilisation. Endurance training is associated with greater bicarbonate labelling, consistent with increased mitochondrial pyruvate utilisation, and reduced lactate production. These metabolic signatures are accompanied by intensity- and training-dependent differences in phosphocreatine degradation and intracellular pH decline measured by ³¹P-MRS. Together, these findings demonstrate the feasibility of combining hyperpolarised ¹³C- and ³¹P-MRS to phenotype skeletal muscle metabolism during exercise, providing a platform for investigating metabolic adaptations in ageing, disease and therapeutic intervention.
Authors
- Matthias Glaser (ORCID: https://orcid.org/0009-0008-4463-989X)
- Stephen Bawden (ORCID: https://orcid.org/0000-0002-5157-3269)
- Sébastien Serres (ORCID: https://orcid.org/0000-0002-1573-1581)
- Jordan McGing (ORCID: https://orcid.org/0000-0002-1238-0472)
- Joanne E. Mallinson (ORCID: https://orcid.org/0000-0003-1275-2448)
- Dorothee P. Auer (ORCID: https://orcid.org/0000-0002-4745-3635)
- Erik Årstad (ORCID: https://orcid.org/0000-0002-3240-2106)
- Andrea Torchi (ORCID: https://orcid.org/0000-0003-3209-055X)
- Andrew Cooper (ORCID: https://orcid.org/0009-0003-0556-1093)
- Ramla Awais
- Dileep N Lobo (ORCID: https://orcid.org/0000-0003-1187-5796)
- Frazer Twyman
- Peter G Morris
- Penny Gowland (ORCID: https://orcid.org/0000-0002-4900-4817)
- Paul L Greenhaff
Institutions
- Nottingham University Hospitals NHS Trust (GB)
- University of Nottingham (GB)
- Singleton Hospital (GB)
- National Institute for Health and Care Research (GB)
- Swansea University (GB)
- University of Oxford (GB)
- Nottingham Biomedical Research Centre (GB)
- University College London (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-10-30
- DOI
- https://doi.org/10.1038/s41467-026-79053-z
- Primary Topic
- Advanced MRI Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Nottingham University Hospitals NHS Trust
- National Institute for Health and Care Research
- University College London
- University of Oxford
- Swansea University
- University College London Hospitals NHS Foundation Trust
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- NIHR Nottingham Biomedical Research Centre