Exercise Metabolism and Adaptation in Skeletal Muscle
Open accessAbstract
Viewing metabolism through the lens of exercise biology has proven an accessible and practical strategy to gain new insights into local and systemic metabolic regulation. Recent methodological developments have advanced understanding of the central role of skeletal muscle in many exercise-associated health benefits and have uncovered the molecular underpinnings driving adaptive responses to training regimens. In this Review, we provide a contemporary view of the metabolic flexibility and functional plasticity of skeletal muscle in response to exercise. First, we provide background on the macrostructure and ultrastructure of skeletal muscle fibres, highlighting the current understanding of sarcomeric networks and mitochondrial subpopulations. Next, we discuss acute exercise skeletal muscle metabolism and the signalling, transcriptional and epigenetic regulation of adaptations to exercise training. We address knowledge gaps throughout and propose future directions for the field. This Review contextualizes recent research of skeletal muscle exercise metabolism, framing further advances and translation into practice.
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Aging is accompanied by progressive decline in physiological resilience, manifesting as impaired metabolic flexibility, reduced skeletal muscle function, chronic low-grade inflammation, and increased susceptibility to sarcopenia, frailty, and cardiometabolic diseases.
“Aging is accompanied by a progressive decline in physiological resilience, often manifesting as impaired metabolic flexibility, reduced skeletal muscle function, chronic low-grade inflammation, and increased susceptibility to sarcopenia, frailty, and cardiometabolic diseases [1].”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [1]
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Roberts, M. D., McCarthy, J. J., Hornberger, T. A., Phillips, S. M., Mackey, A. L., Nader, G. A., Boppart, M. D., Kavazis, A. N., Reidy, P. T., Ogasawara, R., et al. (2023) · Physiological Reviews · doi:10.1152/physrev.00039.2022 · Cited by 214 · see citing works
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Myokines: Metabolic regulation in obesity and type 2 diabetes
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“Aging is accompanied by a progressive decline in physiological resilience, often manifesting as impaired metabolic flexibility, reduced skeletal muscle function, chronic low-grade inflammation, and increased susceptibility to sarcopenia, frailty, and cardiometabolic diseases [1].”
Identification of Genomic Predictors of Muscle Fiber Size
Guilherme, J. P. L. F., Semenova, E. A., Kikuchi, N., Homma, H., Kozuma, A., Saito, M., Zempo, H., Matsumoto, S., Kobatake, N., Nakazato, K., et al. (2024) · Cells · doi:10.3390/cells13141212 · Cited by 11 · see citing works
Xu, M., & Liu, X. (2026) · Biomolecules · doi:10.3390/biom16030406 · Cited by 6 · see citing works
- Authors
- Smith, J. A. B., Murach, K. A., Dyar, K. A., & Zierath, J. R.
- Affiliations
- Karolinska Institutet (SE)
- University of Arkansas at Fayetteville (US)
- Helmholtz Munich (DE)
- University of Copenhagen (DK)
- Corresponding author
- Zierath, Juleen R.
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2023-05-24
- Volume
- 24
- Issue
- 9
- Pages
- 607-632
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- PMC
- PMC10527431
- OpenAlex
- W4377989871
- Cited by
- 342
- References
- 350
- Citations by year
- 2026: 138 · 2025: 113 · 2024: 74 · 2023: 17
- FWCI
- 9.02
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- Novo Nordisk (NNF18CC0034900)
- Vetenskapsrådet (2015-00165)
- Centrum för idrottsforskning (P2022-0013, P2023-0093)
- Novo Nordisk Fonden (NNF 18 CC0034900, NNF22OC0077741)
- Novo Nordisk Foundation Center for Basic Metabolic Research (NNF 18 CC0034900)
- National Institutes of Health (AG063994)
- National Institute on Aging (R00AG063994)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- skeletal muscle metabolism, exercise adaptation, metabolic flexibility, muscle fiber ultrastructure, sarcomere, mitochondrial subpopulations, acute exercise, exercise training, epigenetic regulation, transcriptional regulation, signaling pathways, muscle plasticity
- MeSH terms
- Adaptation, Physiological, Mitochondria, Exercise, Muscle, Skeletal, Epigenesis, Genetic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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