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Peer-reviewedCC BY-NC-NDNature metabolism

Systemic proteomic dynamics of acute exercise reveal genetic links to health and disease.

11 more authors
9 affiliations
  1. 1Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. [email protected].
  2. 2Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
  3. 3Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
  4. 4Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
  5. 5Global translation, Måløv, Denmark.
  6. 6Department of Biology, University of Copenhagen, Copenhagen, Denmark.
  7. 7The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  8. 8Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. [email protected].
  9. 9Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. [email protected].

Abstract

Physical activity improves metabolic health, but the molecular responses that mediate its benefits are not fully characterized. Here we present a high-resolution, time-resolved proteomics atlas across plasma, saliva and urine from 25 healthy men in response to acute exercise. We find that exercise regulates more than 3,000 proteins through distinct, fluid-specific temporal dynamics. Network analysis uncovers coordinated remodelling of protein secretion, extracellular matrix and immune activation across body fluids. Replication in an independent cohort shows that many exercise-responsive plasma proteins exhibit consistent responses across age, sex and exercise modalities. Integration with human genome-wide association study data links secreted, exercise-responsive proteins to cardiometabolic diseases. Functional validation of genetically prioritized muscle-specific secreted proteins in Drosophila confirms their role in endurance, behaviour and metabolism. Overall, this open-access atlas ( https://cbmr.ku.dk/research/research-groups/deshmukh-group/shiny-apps/ ) provides a multifluid resource that complements existing exercise-omics efforts for defining molecular adaptations to exercise and for prioritizing candidate exerkines.

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BibTeX
@article{kurgan2026systemic,
  title = {{Systemic proteomic dynamics of acute exercise reveal genetic links to health and disease.}},
  author = {Nigel Kurgan and Jeppe Kjærgaard and Naja Zenius Jespersen and Virginia Díez-Obrero and Victor Svenstrup and Roger Moreno-Justicia and Sarah Elizabeth Heywood and Cecilie Bergmann Lindqvist and Lisa Ottander and Diana Samodova-Sommer and Alina Malita and Olga Kubrak and Nadja Ahrentløv and Nina Sloth Nielsen and Cody Garett Durrer and Michael Texada and Mathias Ried-Larsen and Simon Rasmussen and Kim Rewitz and Ruth J F Loos and Roelof Adriaan Johan Smit and Bente Klarlund Pedersen and Atul Shahaji Deshmukh},
  journal = {Nature metabolism},
  year = {2026},
  month = oct,
  doi = {10.1038/s42255-026-01621-w},
  url = {https://europepmc.org/article/MED/42864437},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Systemic proteomic dynamics of acute exercise reveal genetic links to health and disease.
AU  - Nigel Kurgan
AU  - Jeppe Kjærgaard
AU  - Naja Zenius Jespersen
AU  - Virginia Díez-Obrero
AU  - Victor Svenstrup
AU  - Roger Moreno-Justicia
AU  - Sarah Elizabeth Heywood
AU  - Cecilie Bergmann Lindqvist
AU  - Lisa Ottander
AU  - Diana Samodova-Sommer
AU  - Alina Malita
AU  - Olga Kubrak
AU  - Nadja Ahrentløv
AU  - Nina Sloth Nielsen
AU  - Cody Garett Durrer
AU  - Michael Texada
AU  - Mathias Ried-Larsen
AU  - Simon Rasmussen
AU  - Kim Rewitz
AU  - Ruth J F Loos
AU  - Roelof Adriaan Johan Smit
AU  - Bente Klarlund Pedersen
AU  - Atul Shahaji Deshmukh
PY  - 2026
DA  - 2026/10/12
JO  - Nature metabolism
DO  - 10.1038/s42255-026-01621-w
UR  - https://europepmc.org/article/MED/42864437
AB  - Physical activity improves metabolic health, but the molecular responses that mediate its benefits are not fully characterized. Here we present a high-resolution, time-resolved proteomics atlas across plasma, saliva and urine from 25 healthy men in response to acute exercise. We find that exercise regulates more than 3,000 proteins through distinct, fluid-specific temporal dynamics. Network analysis uncovers coordinated remodelling of protein secretion, extracellular matrix and immune activation across body fluids. Replication in an independent cohort shows that many exercise-responsive plasma proteins exhibit consistent responses across age, sex and exercise modalities. Integration with human genome-wide association study data links secreted, exercise-responsive proteins to cardiometabolic diseases. Functional validation of genetically prioritized muscle-specific secreted proteins in Drosophila confirms their role in endurance, behaviour and metabolism. Overall, this open-access atlas ( https://cbmr.ku.dk/research/research-groups/deshmukh-group/shiny-apps/ ) provides a multifluid resource that complements existing exercise-omics efforts for defining molecular adaptations to exercise and for prioritizing candidate exerkines.
SN  - 2522-5812
ER  -