Abstract 4143199: The Multi-omic, Multi-tissue Response to Acute Endurance and Resistance Exercise: Results from the Molecular Transducers of Physical Activity Consortium

Introduction: Exercise is critical to cardiovascular health. However, the underlying molecular mechanisms are not well described. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) seeks to create a detailed molecular map of the response to exercise. Described here is the first human cohort of MoTrPAC, enrolled prior to the COVID-19 shutdown (N=175). Methods: Healthy, sedentary adults were randomized to an 8-exercise circuit of resistance exercise (RE, N=73), a 40 minute submaximal endurance exercise bout (EE, N=65), or to non-exercising control (N=37). Blood, muscle, and adipose tissue were sampled at 4-7 time points relative to exercise, depending on tissue/modality. Samples were deep phenotyped across multiple omic domains including chromatin accessibility, transcriptomics, proteomics, phosphoproteomics, and metabolomics. Results: The cohort was 72% female, with a mean±sd age of 41±15 years and BMI of 27.1±4.0 kg/m2. Exercise affected over 34,000 molecular features in ≥1 tissue/time point including a high proportion of transcriptomic and phosphoproteomic features (Figure A). Molecular signatures were compared between EE and RE: enrichment analysis of muscle phosphoproteomics showed a greater activation of MAP kinases in RE compared to EE at all time points. To identify plausible exerkines (secreted molecules signaling an acute exercise bout), differentially abundant features in any sampled tissue cells were compared to temporally-matched cognate protein levels in plasma, yielding 110 features. A known exerkine, CX3CL1 (fractalkine) was identified, in addition to novel candidates, such as cellular communication network factor 1 (CCN1), a secreted extracellular matrix protein linked to plasma triglyceride levels, which showed increased abundance early post exercise (Figure B). Network analysis across tissues and omes identified novel transcription factor “hubs” as candidate master regulators of exercise response. Conclusions: These first MoTrPAC data represent an unparalleled multi-tissue, multi-omic, multi-time point, multi-modality map of acute exercise, enhancing our understanding of the molecular transducers that may link exercise and cardiovascular health.

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Journal
Circulation
Published
2024-11-12
DOI
https://doi.org/10.1161/circ.150.suppl_1.4143199
Citations
2
Primary Topic
Exercise and Physiological Responses
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article
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Abstract 4143199: The Multi-omic, Multi-tissue Response to Acute Endurance and Resistance Exercise: Results from the Molecular Transducers of Physical Activity Consortium

Christopher Jin, Jeremy Robbins, Fang‐Chi Hsu, Archana N. Raja et al.
2 citations
Circulation
Exercise and Physiological Responses
0.50
article

Abstract 4143199: The Multi-omic, Multi-tissue Response to Acute Endurance and Resistance Exercise: Results from the Molecular Transducers of Physical Activity Consortium

Christopher Jin, Jeremy Robbins, Fang‐Chi Hsu, Archana N. Raja, Gregory R. Smith, David Amar, Jacob L. Barber, Jerome L. Fleg, Scott Trappe, Zidong Zhang, Michael Snyder, Stephen B. Montgomery, Lauren Marie Sparks, Yongchao Ge, Steven A. Carr, Daniel H. Katz, James Sanford, Natalie M. Clark, Byron C. Jaeger, Hasmik Keshishian, Russell P. Tracy, Matthew T. Wheeler, Charles Burant, Samuel Montalvo, Stuart C. Sealfon, Ashley Xia, David Jimenez‐Morales, Maléne E. Lindholm, Gayatri Iyer, Bret H. Goodpaster, Tyler J. Sagendorf, Jimmy Zhen, Euan Angus Ashley, Gina M. Many, Martin J. Walsh, Nikolai G. Vetr, Joshua Adkins, Patrick J. Hart, Michael E. Miller, Kevin S. Smith, Robert Gerszten, MoTrPAC Study Group .
article en
2 citations

Abstract

Introduction: Exercise is critical to cardiovascular health. However, the underlying molecular mechanisms are not well described. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) seeks to create a detailed molecular map of the response to exercise. Described here is the first human cohort of MoTrPAC, enrolled prior to the COVID-19 shutdown (N=175). Methods: Healthy, sedentary adults were randomized to an 8-exercise circuit of resistance exercise (RE, N=73), a 40 minute submaximal endurance exercise bout (EE, N=65), or to non-exercising control (N=37). Blood, muscle, and adipose tissue were sampled at 4-7 time points relative to exercise, depending on tissue/modality. Samples were deep phenotyped across multiple omic domains including chromatin accessibility, transcriptomics, proteomics, phosphoproteomics, and metabolomics. Results: The cohort was 72% female, with a mean±sd age of 41±15 years and BMI of 27.1±4.0 kg/m2. Exercise affected over 34,000 molecular features in ≥1 tissue/time point including a high proportion of transcriptomic and phosphoproteomic features (Figure A). Molecular signatures were compared between EE and RE: enrichment analysis of muscle phosphoproteomics showed a greater activation of MAP kinases in RE compared to EE at all time points. To identify plausible exerkines (secreted molecules signaling an acute exercise bout), differentially abundant features in any sampled tissue cells were compared to temporally-matched cognate protein levels in plasma, yielding 110 features. A known exerkine, CX3CL1 (fractalkine) was identified, in addition to novel candidates, such as cellular communication network factor 1 (CCN1), a secreted extracellular matrix protein linked to plasma triglyceride levels, which showed increased abundance early post exercise (Figure B). Network analysis across tissues and omes identified novel transcription factor “hubs” as candidate master regulators of exercise response. Conclusions: These first MoTrPAC data represent an unparalleled multi-tissue, multi-omic, multi-time point, multi-modality map of acute exercise, enhancing our understanding of the molecular transducers that may link exercise and cardiovascular health.

CirculationVol. 150(Suppl_1)
Broad Institute (US), University of Vermont (US), National Institutes of Health (US), Beth Israel Deaconess Medical Center (US), Pacific Northwest National Laboratory (US), Ball State University (US), University of Michigan (US), National Heart, Lung, and Blood Institute (US), Michigan United (US), Wake Forest University (US), Stanford University (US), Icahn School of Medicine at Mount Sinai (US)
Good health and well-being
Openalex Percentile: Top 29%
Exercise and Physiological Responses
0.50
DOISourceOpenAlex
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