Temporal dynamics of the multi-omic response to endurance exercise training across tissues

• DOI: 10.1101/2022.09.21.508770
• Publication Date: 2022-09-23T14:45:12Z
• Authors: David Amar; Nicole R. Gay; Pierre M. Jean Be...; Joshua N. Adkins; Jose J. Almagro A...; Euan Ashley; Julian Avila-Pacheco; Dam Bae; Nasim Bararpour; Charles Burant; Clary Clish; Gary Cutter; Surendra Dasari; Courtney Dennis; Charles R. Evans; Facundo M. Fernández; David Gaul; Yongchao Ge; Robert Gerszten; Laurie J. Goodyear; Zhenxin Hou; Olga Ilkayeva; Anna A. Ivanova; David Jimenez-Mor...; Maureen T. Kachman; Hasmik Keshishian; William E. Kraus; Ian R. Lanza; Jun Li; Malene E. Lindholm; Ana C. Lira; Gina M. Many; Shruti Marwaha; Michael E. Miller; Michael J. Muehlb...; K. Sreekumaran Nair; Venugopalan D. Nair; Archana Natarajan...; Christopher Newgard; Eric A. Ortlund; Paul D. Piehowski; David M. Presby; Wei-Jun Qian; Jessica L. Rooney; James A. Sanford; Evan Savage; Stuart C. Sealfon; Gregory R. Smith; Kevin S. Smith; Alec Steep; Cynthia L. Stowe; Yifei Sun; Russell Tracy; Nikolai G. Vetr; Martin J. Walsh; Si Wu; Tiantian Zhang; Bingqing Zhao; Jimmy Zhen; Brent G. Albertson; Mary Anne S. Amper; Ali Tugrul Balci; Marcas Bamman; Elisabeth R. Barton; Bryan Bergman; Daniel Bessesen; Frank Booth; Brian Bouverat; Thomas W. Buford; Tiziana Caputo; Toby L. Chambers; Clarisa Chavez; Maria Chikina; Roxanne Chiu; Michael Cicha; Paul M. Coen; Dan Cooper; Elaine Cornell; Karen P. Dalton; Luis Oliveria De ...; Roger Farrar; Kishore Gadde; Nicole Gagne; Bret H. Goodpaster; Marina A. Gritsenko; Kristy Guevara; Fadia Haddad; Joshua R. Hansen; Melissa Harris; Trevor Hastie; Krista M. Hennig; Steven G. Hershman; Andrea Hevener; Michael F. Hirshman; Fang-Chi Hsu; Kim M. Huffman; Chia-Jui Hung; Chelsea Hutchinso...; Bailey E. Jackson; Catherine Jankowski; Christopher A. Jin; Neil M. Johannsen; Benjamin G. Ke; Wendy M. Kohrt; Kyle S. Kramer; Christiaan Leeuwe...; Sarah J. Lessard; Bridget Lester; Xueyun Liu; Ching-ju Lu; Nathan S. Makarewicz; Kristal M. Maner-...; DR Mani; Nada Marjanovic; Andrea Marshall; Sandy May; Edward Melanson; Matthew E. Monroe; Ronald J. Moore; Samuel Moore; Kerrie L. Moreau; Charles C. Mundorff; Nicolas Musi; Daniel Nachun; Michael D. Nestor; Robert L. Newton; Barbara Nicklas; Pasquale Nigro; German Nudelman; Marco Pahor; Cadence Pearce; Vladislav A. Petyuk; Hanna Pincas; Scott Powers; Shlomit Radom-Aizik; Krithika Ramachan...; Megan E. Ramaker; Irene Ramos; Tuomo Rankinen; Alexander (Sasha)...; Blake B. Rasmussen; Eric Ravussin; R. Scott Rector; W. Jack Rejeski; Collyn Richards; Stas Rirak; Jeremy M. Robbins; Aliza B. Rubenstein; Frederique Ruf-Za...; Scott Rushing; Tyler J. Sagendorf; Mihir Samdarshi; Irene E. Schauer; Robert Schwartz; Nitish Seenarine; Tanu Soni; Lauren M. Sparks; Christopher Teng; Anna Thalacker-Me...; John Thyfault; Rob Tibshirani; Scott Trappe; Todd A. Trappe; Karan Uppal; Sindhu Vangeti; Mital Vasoya; Elena Volpi; Alexandria Vornholt; Michael P. Walkup; John Williams; Ashley Xia; Zhen Yan; Xuechen Yu; Chongzhi Zang; Elena Zaslavsky; Navid Zebarjadi; Sue C. Bodine; Steven Carr; Karyn Esser; Stephen B. Montgo...; Simon Schenk; Michael P. Snyder; Matthew T. Wheeler
• Keywords: Endurance Training; Metabolome; Lipidome; Proteome

Abstract Regular exercise promotes whole-body health and prevents disease, yet the underlying molecular mechanisms throughout a whole organism are incompletely understood. Here, Molecular Transducers of Physical Activity Consortium (MoTrPAC) profiled temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome, immunome in blood, plasma, 18 solid tissues Rattus norvegicus over 8 weeks endurance training. The resulting data compendium encompasses 9466 assays across 19 tissues, 25 platforms, 4 training time points young adult male female rats. We identified thousands shared tissue- sex-specific alterations. Temporal multi-omic multi-tissue analyses demonstrated distinct patterns tissue remodeling, with widespread regulation immune, metabolism, heat shock stress response, mitochondrial pathways. These provide biological insights into adaptive responses to time. For example, induced heart remodeling via altered activity Mef2 family transcription factors tyrosine kinases. Translational revealed changes that consistent human negatively correlated including increased phospholipids decreased triacylglycerols liver. Sex differences adaptation were widespread, those brain, adrenal gland, lung, adipose tissue. Integrative generated novel hypotheses disease relevance, candidate link non-alcoholic fatty liver inflammatory bowel cardiovascular health, injury recovery. analysis results presented this study will serve as valuable resources for broader community provided an easily accessible public repository ( https://motrpac-data.org/ ). Highlights Multi-tissue resource identifies 35,439 analytes regulated by at 5% FDR 211 combinations platforms. Interpretation systemic tissue-specific adaptations produced help describe benefits exercise. Robust observed multiple organs level. Deep profiling six defines regulatory signals All available repository, processed data, results, code reproduce major additionally convenient R packages.