Multi-Omic, Multi-Tissue Responses to Acute Exercise in Sedentary Adults: Findings from the Molecular Transducers of Physical Activity Consortium

MoTrPAC Study Group,; Katz, D. H.; Jin, C. A.; Many, G. M.; Smith, G. R.; Keshishian, H.; Clark, N. M.; Iyer, G.; Ahn, C.; Lindholm, M. E.; Sagendorf, T. J.; Amar, D.; Barber, J. L.; Brandt, A. R.; Coen, P. M.; Ge, Y.; Hart, P.; Hsu, F.-C.; Jaeger, B. C.; Jimenez-Morales, D.; Leach, D. T.; Mani, D. R.; Montalvo, S.; Pincas, H.; Rao, P.; Sanford, J. A.; Smith, K. S.; Vetr, N. G.; Adkins, J. N.; Ashley, E. A.; Carr, S. A.; Miller, M. E.; Montgomery, S. B.; Nair, V. D.; Robbins, J. M.; Snyder, M. P.; Sparks, L. M.; Tracy, R.; Walsh, M. J.; Wheeler, M. T.; Xia, A. Y.; Sealfon, S. C.; Gerszten, R

doi:10.64898/2026.02.27.702183

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bioRxiv · 10.64898/2026.02.27.702183

Multi-Omic, Multi-Tissue Responses to Acute Exercise in Sedentary Adults: Findings from the Molecular Transducers of Physical Activity Consortium

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Abstract

Regular physical activity represents one of the greatest mechanisms for maintaining human health, yet the underlying molecular transducers of these benefits remain incompletely understood. Multi-omic assays now provide new opportunities to study the coordinated molecular responses of body tissues to different exercise modalities. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this need by creating a molecular map of the response to physical activity. Described here is the first human cohort of MoTrPAC: sedentary adults enrolled prior to study suspension during the COVID-19 pandemic (N=175) randomized to either endurance or resistance exercise, or non-exercise control. From these participants, we detail their global acute molecular response in skeletal muscle, adipose tissue, and blood, integrated at multiple levels: tissue, exercise modality, timepoint, and omic category. These analyses characterize key molecular pathways, identify central regulators, and implicate novel candidate exerkines in mediating multi-organ exercise effects.

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MoTrPAC Study Group,, Katz, D. H., Jin, C. A., Many, G. M., Smith, G. R., Keshishian, H., Clark, N. M., Iyer, G., Ahn, C., Lindholm, M. E., Sagendorf, T. J., Amar, D., Barber, J. L., Brandt, A. R., Coen, P. M., Ge, Y., Hart, P., Hsu, F.-C., Jaeger, B. C., Jimenez-Morales, D., Leach, D. T., Mani, D. R., Montalvo, S., Pincas, H., Rao, P., Sanford, J. A., Smith, K. S., Vetr, N. G., Adkins, J. N., Ashley, E. A., Carr, S. A., Miller, M. E., Montgomery, S. B., Nair, V. D., Robbins, J. M., Snyder, M. P., Sparks, L. M., Tracy, R., Walsh, M. J., Wheeler, M. T., Xia, A. Y., Sealfon, S. C., Gerszten, R. 2026-03-03. Multi-Omic, Multi-Tissue Responses to Acute Exercise in Sedentary Adults: Findings from the Molecular Transducers of Physical Activity Consortium. https://doi.org/10.64898/2026.02.27.702183

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