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)
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,
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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.
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