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Integrative Multi-omics Analysis of the Human Skeletal Muscle Response to Endurance or Resistance Exercise: Findings from the Molecular Transducers of Physical Activity Consortium (MoTrPAC).

Integrative Multi-omics Analysis of the Human Skeletal Muscle Response to Endurance or Resistance Exercise: Findings from the Molecular Transducers of Physical Activity Consortium (MoTrPAC). bioRxiv : the preprint server for biology Keshishian, H., Many, G. M., Smith, G., Clark, N. M., Iyer, G., Hart, P., Lindholm, M. E., Montalvo, S., Zhang, Z., Jin, C., Sanford, J. A., Carr, S. A., Adkins, J. N., Mani, D. R., Bodine, S. C., Trappe, S., Houmard, J. A., Musi, N., Huffman, K. M., Kraus, W. E., Sparks, L. M., Thalacker-Mercer, A. E., Sealfon, S. C., Xia, A. Y., Katz, D. H., Newgard, C. B., Burant, C. F., Coen, P. M., Goodpaster, B. H., MoTrPAC Study Group 2026

Abstract

The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to systematically characterize the molecular basis of the health benefits of exercise. Here, we present the integrative, multi-omics response of human skeletal muscle to acute endurance (EE) and resistance (RE) exercise. Distinct temporal responses were observed, with changes in ATAC-seq, phosphoproteome, and metabolome occurring before changes in the transcriptome and proteome. These distinct temporal multi-omic dynamics were used to identify transcriptional regulatory hubs converging around MEF2A and NFIC regulation of autophagy, angiogenesis and metabolism. Further, early RE-specific phosphoproteome signatures counteracted epigenetic modifications and downregulated transcripts involved in protein turnover. Additional findings include suppression of HIPK2/3 kinase signatures linked to the acute exercise regulation of sarcomeric proteins TTN, NEB, ANKRD2 and LMOD2. Our data demonstrate distinct temporal regulation across the multi-omic landscape of human skeletal muscle, with EE and RE eliciting common and unique molecular signatures.

View details for DOI 10.64898/2026.03.04.705181

View details for PubMedID 41867825