Gina M Many, Christopher Jin, Nicholas J Day, Gayatri Iyer, Gregory Smith, Kayleigh Voos, James A Sanford, Akshay Bareja, David Jimenez-Morales, Damon T Leach, Tyler J Sagendorf, Abdalla Ahmed, Xiaolu Li, Matthew J Gaffrey, Isaac K Attah, Hugh D Mitchell, Mark R Viggars, David Gaul, Kim M Huffman, Facundo Fernández, Michael P Snyder, Eric Ortlund, Wendy Kohrt, Matthew T Wheeler, William E Kraus, Karyn A Esser, Bret H Goodpaster, Laurie J Goodyear, Charles F Burant, Christopher B Newgard, Andrea L Hevener, Sue C Bodine, Wei-Jun Qian, Simon Schenk, Joshua N Adkins, Malene E Lindholm, MoTrPAC study group
Exercise training confers broad health benefits, yet molecular regulators of skeletal muscle adaptation, particularly sex-specific mechanisms, remain incompletely understood. Integrating new and previously published multi-omics data from the molecular transducers of physical activity consortium (MoTrPAC), we characterized metabolomic, epigenomic, transcriptomic, proteomic, and post-translational modification (PTM) responses to 1-8 weeks of endurance exercise training in male and female rat gastrocnemius. While transcriptomic and proteomic responses were largely sex-concordant, there were distinct sex-specific training-induced PTM signatures, particularly in the redox proteome. Females exhibited decreased mitochondrial protein cysteine oxidation alongside increased oxidation of glycolytic proteins relative to males, suggesting sex-biased subcellular reactive oxygen species (ROS) dynamics. Multi-omic factor analysis (MOFA) identified coordinated sex-concordant molecular programs and further supported female-specific mechanisms of redox buffering with training. Together, these findings indicate that sex-specific skeletal muscle exercise adaptations are particularly evident at the PTM level in rats, and identify future avenues for precision exercise health and medicine.