Blood Biochemical Responses to Acute Exercise: Findings from the Molecular Transducers of Physical Activity Consortium (MoTrPAC)

Abstract Exercise benefits numerous organ systems and tissues, however limited knowledge exists about its underlying molecular pathways. Identifying the exercise-induced biochemical changes that occur in the circulation may provide further insights into how exercise confers systemic health changes. Here, we perform large-scale plasma proteomic, metabolomic, and whole blood transcriptional profiling in sedentary human participants undergoing acute endurance exercise (EE), resistance exercise (RE), or a non-exercise control (CON) in up to 7 timepoints over a 24 hour period. We observe 7066 transcript, 189 protein, and 448 metabolite changes in response to EE or RE compared to CON. Our analyses reveal numerous shared biochemical responses between EE and RE modes, but also differences in immune cell responses, lipid metabolism, and pathways reflective of tissue repair and angiogenesis. Taken together, our findings highlight novel temporal and exercise mode-specific blood-based molecular responses to acute exercise, and provide a new resource for the scientific community. Competing Interest Statement Euan A. Ashley is Founder: Personalis, Deepcell, Svexa, Saturnus Bio, Swift Bio. Founder Advisor: Candela, Parameter Health. Advisor: Pacific Biosciences. Non-executive director: AstraZeneca, Dexcom. Publicly traded stock: Personalis, Pacific Biosciences, AstraZeneca. Collaborative support in kind: Illumina, Pacific Biosciences, Oxford Nanopore, Cache, Cellsonics Stephen A. Carr is on the scientific advisory boards of PrognomIQ, MOBILion Systems, Kymera, and Stand Up2 Cancer. Pierre Jean Beltran is currently an employee at Pfizer, Inc. Bret H. Goodpaster has served as a member of scientific advisory boards. Byron Jaeger receives consulting fees from Perisphere Real World Evidence, LLC, unrelated to this project. Stephen B. Montgomery is a member of the scientific advisory board for PhiTech, MyOme and Valinor Therapeutics. Gary R Cutter is a part of: Data and Safety Monitoring Boards: Applied Therapeutics, AI therapeutics, Amgen-NMO peds, AMO Pharma, Argenx, Astra-Zeneca, Bristol Meyers Squibb, CSL Behring, DiamedicaTherapeutics, Horizon Pharmaceuticals, Immunic, Inhrbx-sanfofi, Karuna Therapeutics, Kezar Life Sciences, Medtronic, Merck, Meiji Seika Pharma, Mitsubishi Tanabe Pharma Holdings, Prothena Biosciences, Novartis, Pipeline Therapeutics (Contineum), Regeneron, Sanofi-Aventis, Teva Pharmaceuticals, United BioSource LLC, University of Texas Southwestern, Zenas Biopharmaceuticals. Consulting or Advisory Boards: Alexion, Antisense Therapeutics/Percheron, Avotres, Biogen, Clene Nanomedicine, Clinical Trial Solutions LLC, Endra Life Sciences, Genzyme, Genentech, Immunic, Klein-Buendel Incorporated, Kyverna Therapeutics, Inc., Linical, Merck/Serono, Noema, Neurogenesis, Perception Neurosciences, Protalix Biotherapeutics, Regeneron, Revelstone Consulting, Roche, Sapience Therapeutics, Tenmile. Dr. Cutter is employed by the University of Alabama at Birmingham and President of Pythagoras, Inc. a private consulting company located in Birmingham AL. John M. Jakicic is on the Scientific Advisory Board for Wondr Health, Inc. Erin E. Kershaw is a consultant for NodThera and Sparrow Pharmaceuticals and a site PI for clinical trials for Arrowhead Pharmaceuticals. Bradly. C. Nindl is member of the Science Advisory Council, Institute of Human and Machine Cognition, Pensacola, FL. Jeremy M. Robbins is a consultant for Edwards Lifesciences; Abbott Laboratories; Janssen Pharmaceuticals. Renee Rogers is a scientific advisor to AstraZeneca, Neurocrine Biosciences, and the American Council on Exercise, and a consultant to Wonder Health, Inc. and Seca. Stuart C. Sealfon is a founder of GNOMX Corp, leads its scientific advisory board and serves as its temporary Chief Scientific Officer. Michael P. Snyder is a cofounder and shareholder of January AI. Alexandria Vornholt is a consultant for GNOMX Corp. Footnotes The MoTrPAC Study Group author list has been updated.