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Molecular Choreography of Acute Exercise
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Abstract
Acute physical activity leads to several changes in metabolic, cardiovascular, and immune pathways. Although studies have examined selected changes in these pathways, the system-wide molecular response to an acute bout of exercise has not been fully characterized. We performed longitudinal multi-omic profiling of plasma and peripheral blood mononuclear cells including metabolome, lipidome, immunome, proteome, and transcriptome from 36 well-characterized volunteers, before and after a controlled bout of symptom-limited exercise. Time-series analysis revealed thousands of molecular changes and an orchestrated choreography of biological processes involving energy metabolism, oxidative stress, inflammation, tissue repair, and growth factor response, as well as regulatory pathways. Most of these processes were dampened and some were reversed in insulin-resistant participants. Finally, we discovered biological pathways involved in cardiopulmonary exercise response and developed prediction models revealing potential resting blood-based biomarkers of peak oxygen consumption.
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“the increases of acute inflammatory markers seen during exercise (e.g., IL-6, TNF-a, IL1-RA, and IGF-1) could be problematic to an already increased inflammatory pattern we measured in astronauts (Fig. 5B), even though these markers are reduced by regular exercise in low-grade systemic inflammation patients (Contrepois et al., 2020; Khazaei, 2012).”
From Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact (2020) · cites this paper as Contrepois et al., 2020
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“A study on acute exercise in individuals with a spectrum of insulin resistance showed that acute physical activity triggers molecular responses on the metabolic and energy-producing pathways, increasing glycolysis, TCA cycle, and fatty acid oxidation (Contrepois et al., 2020).”
From Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact (2020) · cites this paper as Contrepois et al., 2020
In the citing paper
“A seminal work by Contrepois et al. [643] found that a simple amount of acute exercise (and up to 1 -h recovery after the training in individulas aged 40–75 years) induced substantial changes in more than half (n = 9,816 analytes) of the 17,662 analytes evaluated through a multi-omics approach.”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [643]
In the citing paper
“A seminal work by Contrepois et al. [643] found that a simple amount of acute exercise (and up to 1 -h recovery after the training in individulas aged 40–75 years) induced substantial changes in more than half (n = 9,816 analytes) of the 17,662 analytes evaluated through a multi-omics approach.”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [643]
In the citing paper
“Acute exercise creates a unique exerkine milieu that lasts several hours after exercise cessation, which provides a temporal window for immune function stimulation31.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [31]
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Exerkines in health, resilience and disease
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Metadata
- Authors
- Contrepois, K., Wu, S., Moneghetti, K. J., Hornburg, D., Ahadi, S., Tsai, M.-S., Metwally, A. A., Wei, E., Lee-McMullen, B., Quijada, J. V., Chen, S., Christle, J. W., Ellenberger, M., Balliu, B., Taylor, S., Durrant, M. G., Knowles, D. A., Choudhry, H., Ashland, M., Bahmani, A., Enslen, B., Amsallem, M., Kobayashi, Y., Avina, M., Perelman, D., Schüssler-Fiorenza Rose, S. M., Zhou, W., Ashley, E. A., Montgomery, S. B., Chaib, H., Haddad, F., & Snyder, M. P.
- Affiliations
- Stanford Medicine (US)
- The University of Melbourne (AU)
- King Abdulaziz University (SA)
- Corresponding author
- Snyder, Michael P.
- ORCID
- Contrepois, Kévin
- Wu, Si
- Moneghetti, Kegan J.
- Hornburg, Daniel
- Ahadi, Sara
- Metwally, Ahmed A.
- Chen, Songjie
- Christle, Jeffrey W.
- Ellenberger, Mathew
- Balliu, Brunilda
- Taylor, Shalina
- Durrant, Matthew G.
- Knowles, David A.
- Choudhry, Hani
- Ashland, Melanie
- Bahmani, Amir
- Amsallem, Myriam
- Kobayashi, Yukari
- Perelman, Dalia
- Zhou, Wenyu
- Ashley, Euan A.
- Montgomery, Stephen B.
- Snyder, Michael P.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-05
- Volume
- 181
- Issue
- 5
- Pages
- 1112-1130.e16
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7299174
- OpenAlex
- W3029490310
- Cited by
- 502
- References
- 128
- Citations by year
- 2026: 90 · 2025: 90 · 2024: 78 · 2023: 80 · 2022: 79 · 2021: 71 · 2020: 13
- FWCI
- 33.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, other-oa)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Stanford Diabetes Research Center
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Physical Activity and Health
- Keywords
- acute exercise, multi-omics profiling, plasma metabolome, lipidome, peripheral blood mononuclear cells, immunome, proteome, transcriptome, energy metabolism, oxidative stress, inflammation, tissue repair, growth factor responsiveness, insulin resistance, peak oxygen uptake, blood-based biomarkers
- MeSH terms
- Aged, Energy Metabolism, Female, Humans, Insulin, Insulin Resistance, Leukocytes, Mononuclear, Longitudinal Studies, Male, Middle Aged, Oxygen, Oxygen Consumption, Biomarkers, Exercise, Proteome, Metabolome, Transcriptome
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