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

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

doi:10.1038/s41586-023-06877-w

Title: Temporal dynamics of the multi-omic response to endurance exercise training

Journal Article · 30 April 2024 · Nature (London)

DOI: https://doi.org/10.1038/s41586-023-06877-w · OSTI ID:2471552

;

; Bae, Dam; Dasari, Surendra; Dennis, Courtney; Evans, Charles R.;

;

; Ivanova, Anna A.;

; Keshishian, Hasmik; Lanza, Ian R.; Lira, Ana C.; Muehlbauer, Michael J.;

;

; Rooney, Jessica L.; Smith, Kevin S.;

Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood. Here, the Molecular Transducers of Physical Activity Consortium profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository (https://motrpac-data.org/).

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

Contributing Organization:: MoTrPAC Study Group

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2471552

Journal Information:: Nature (London), Journal Name: Nature (London) Journal Issue: 8010 Vol. 629; ISSN 0028-0836

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

References (36)

Visualization of graphical analysis results: Temporal dynamics of the multi-omic response to endurance exercise training across tissues Gay, Nicole R.; Amar, David; Group, MoTrPAC Study Zenodo https://doi.org/10.5281/zenodo.7703294	other	January 2023
Physical Fitness and All-Cause Mortality: A Prospective Study of Healthy Men and Women Blair, Steven N. JAMA, Vol. 262, Issue 17 https://doi.org/10.1001/jama.1989.03430170057028	journal	November 1989
Lack of Exercise Is a Major Cause of Chronic Diseases Booth, Frank W.; Roberts, Christian K.; Laye, Matthew J. Comprehensive Physiology https://doi.org/10.1002/cphy.c110025	book	January 2012
Preischemic exercise reduces brain damage by ameliorating metabolic disorder in ischemia/reperfusion injury Dornbos, David; Zwagerman, Nathan; Guo, Miao Journal of Neuroscience Research, Vol. 91, Issue 6 https://doi.org/10.1002/jnr.23203	journal	March 2013
The BioGRID database: A comprehensive biomedical resource of curated protein, genetic, and chemical interactions Oughtred, Rose; Rust, Jennifer; Chang, Christie Protein Science, Vol. 30, Issue 1 https://doi.org/10.1002/pro.3978	journal	November 2020
Effect of exercise on plasma kallikrein and muscular phospholipase A2 activity in rats Vettor, R.; De Palo, C.; Caló, L. Molecular and Cellular Endocrinology, Vol. 45, Issue 1 https://doi.org/10.1016/0303-7207(86)90083-3	journal	April 1986
The Epithelial Danger Signal IL-1α Is a Potent Activator of Fibroblasts and Reactivator of Intestinal Inflammation Scarpa, Melania; Kessler, Sean; Sadler, Tammy The American Journal of Pathology, Vol. 185, Issue 6 https://doi.org/10.1016/j.ajpath.2015.02.018	journal	June 2015
Phenotypic Characterization and Comparison of Cystic Fibrosis Rat Models Generated Using CRISPR/Cas9 Gene Editing McCarron, Alexandra; Cmielewski, Patricia; Reyne, Nicole The American Journal of Pathology, Vol. 190, Issue 5 https://doi.org/10.1016/j.ajpath.2020.01.009	journal	May 2020
Maximal Oxidative Capacity during Exercise Is Associated with Skeletal Muscle Fuel Selection and Dynamic Changes in Mitochondrial Protein Acetylation Overmyer, Katherine A.; Evans, Charles R.; Qi, Nathan R. Cell Metabolism, Vol. 21, Issue 3 https://doi.org/10.1016/j.cmet.2015.02.007	journal	March 2015
Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits Neufer, P. Darrell; Bamman, Marcas M.; Muoio, Deborah M. Cell Metabolism, Vol. 22, Issue 1 https://doi.org/10.1016/j.cmet.2015.05.011	journal	July 2015
Atlas of exercise metabolism reveals time-dependent signatures of metabolic homeostasis Sato, Shogo; Dyar, Kenneth A.; Treebak, Jonas T. Cell Metabolism, Vol. 34, Issue 2 https://doi.org/10.1016/j.cmet.2021.12.016	journal	February 2022
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease Wang, Zeneng; Klipfell, Elizabeth; Bennett, Brian J. Nature, Vol. 472, Issue 7341 https://doi.org/10.1038/nature09922	journal	April 2011
Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease Jostins, Luke; Ripke, Stephan; Weersma, Rinse K. Nature, Vol. 491, Issue 7422 https://doi.org/10.1038/nature11582	journal	October 2012
Transcriptomic profiling of skeletal muscle adaptations to exercise and inactivity Pillon, Nicolas J.; Gabriel, Brendan M.; Dollet, Lucile Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-019-13869-w	journal	January 2020
Time trajectories in the transcriptomic response to exercise - a meta-analysis Amar, David; Lindholm, Malene E.; Norrbom, Jessica Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-23579-x	journal	June 2021
Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue Many, Gina M.; Sanford, James A.; Sagendorf, Tyler J. Nature Metabolism, Vol. 6, Issue 5 https://doi.org/10.1038/s42255-023-00959-9	journal	May 2024
Gliadin Induces an Increase in Intestinal Permeability and Zonulin Release by Binding to the Chemokine Receptor CXCR3 Lammers, Karen M.; Lu, Ruliang; Brownley, Julie Gastroenterology, Vol. 135, Issue 1 https://doi.org/10.1053/j.gastro.2008.03.023	journal	July 2008
v-Src phosphorylation of connexin 43 on Tyr247 and Tyr265 disrupts gap junctional communication Lin, Rui; Warn-Cramer, Bonnie J.; Kurata, Wendy E. The Journal of Cell Biology, Vol. 154, Issue 4 https://doi.org/10.1083/jcb.200102027	journal	August 2001
DOSE: an R/Bioconductor package for disease ontology semantic and enrichment analysis Yu, Guangchuang; Wang, Li-Gen; Yan, Guang-Rong Bioinformatics, Vol. 31, Issue 4 https://doi.org/10.1093/bioinformatics/btu684	journal	October 2014
Association of physical activity with all-cause and cardiovascular mortality: a systematic review and meta-analysis Nocon, Marc; Hiemann, Theresa; Müller-Riemenschneider, Falk European Journal of Cardiovascular Prevention & Rehabilitation, Vol. 15, Issue 3 https://doi.org/10.1097/HJR.0b013e3282f55e09	journal	June 2008
Exercise and Hematopoietic Stem and Progenitor Cells De Lisio, Michael; Parise, Gianni Exercise and Sport Sciences Reviews, Vol. 41, Issue 2 https://doi.org/10.1097/JES.0b013e3182877deb	journal	April 2013
Exercise as medicine – evidence for prescribing exercise as therapy in 26 different chronic diseases Pedersen, B. K.; Saltin, B. Scandinavian Journal of Medicine & Science in Sports, Vol. 25, Issue S3 https://doi.org/10.1111/sms.12581	journal	November 2015
Exercise and associated dietary extremes impact on gut microbial diversity Clarke, Siobhan F.; Murphy, Eileen F.; O'Sullivan, Orla Gut, Vol. 63, Issue 12 https://doi.org/10.1136/gutjnl-2013-306541	journal	June 2014
Heat shock proteins and exercise adaptations. Our knowledge thus far and the road still ahead Henstridge, Darren C.; Febbraio, Mark A.; Hargreaves, Mark Journal of Applied Physiology, Vol. 120, Issue 6 https://doi.org/10.1152/japplphysiol.00811.2015	journal	March 2016
Role of kallikrein-kininogen system in insulin-stimulated glucose transport after muscle contractions Dumke, C. L.; Kim, J.; Arias, E. B. Journal of Applied Physiology, Vol. 92, Issue 2 https://doi.org/10.1152/japplphysiol.00854.2001	journal	February 2002
Gene expression profiling of skeletal muscle in exercise-trained and sedentary rats with inborn high and low VO_2max Bye, Anja; Høydal, Morten A.; Catalucci, Daniele Physiological Genomics, Vol. 35, Issue 3 https://doi.org/10.1152/physiolgenomics.90282.2008	journal	November 2008
Heart Failure, Diabetes Mellitus, and Chronic Kidney Disease Aguilar, David Circulation: Heart Failure, Vol. 9, Issue 7 https://doi.org/10.1161/CIRCHEARTFAILURE.116.003316	journal	July 2016
Exercise-Induced Changes in Glucose Metabolism Promote Physiological Cardiac Growth Gibb, Andrew A.; Epstein, Paul N.; Uchida, Shizuka Circulation, Vol. 136, Issue 22 https://doi.org/10.1161/CIRCULATIONAHA.117.028274	journal	November 2017
Desmoplakin: An Important Player in Aging Lung Disease van Moorsel, Coline H. M. American Journal of Respiratory and Critical Care Medicine, Vol. 202, Issue 9 https://doi.org/10.1164/rccm.202006-2457ED	journal	November 2020
Myosin light chain kinase (MYLK) coding polymorphisms modulate human lung endothelial cell barrier responses via altered tyrosine phosphorylation, spatial localization, and lamellipodial protrusions Wang, Ting; Brown, Mary E.; Kelly, Gabriel T. Pulmonary Circulation, Vol. 8, Issue 2 https://doi.org/10.1177/2045894018764171	journal	March 2018
MEF2C Enhances Dopaminergic Neuron Differentiation of Human Embryonic Stem Cells in a Parkinsonian Rat Model Cho, Eun-Gyung; Zaremba, Jeffrey D.; McKercher, Scott R. PLoS ONE, Vol. 6, Issue 8 https://doi.org/10.1371/journal.pone.0024027	journal	August 2011
Exercise Combats Hepatic Steatosis: Potential Mechanisms and Clinical Implications Thyfault, John P.; Rector, R. Scott Diabetes, Vol. 69, Issue 4 https://doi.org/10.2337/dbi18-0043	journal	March 2020
An integrative analysis reveals coordinated reprogramming of the epigenome and the transcriptome in human skeletal muscle after training Lindholm, Maléne E.; Marabita, Francesco; Gomez-Cabrero, David Epigenetics, Vol. 9, Issue 12 https://doi.org/10.4161/15592294.2014.982445	journal	December 2014
Visualization of graphical analysis results: Temporal dynamics of the multi-omic response to endurance exercise training across tissues Gay, Nicole R.; Amar, David; Group, MoTrPAC Study Zenodo https://doi.org/10.5281/zenodo.7703294	other	January 2023
An integrative analysis reveals coordinated reprogramming of the epigenome and the transcriptome in human skeletal muscle after training Lindholm, Maléne E.; Marabita, Francesco; Gomez-Cabrero, David Taylor & Francis https://doi.org/10.6084/m9.figshare.1263588	dataset	January 2014
High-intensity interval training remodels the proteome and acetylome of human skeletal muscle Hostrup, Morten; Lemminger, Anders Krogh; Stocks, Ben eLife, Vol. 11 https://doi.org/10.7554/eLife.69802	journal	May 2022

Similar Records

Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise

Journal Article · 2020 · Cell · OSTI ID:1760420

Sanford, James A.; Nogiec, Christopher D.; Lindholm, Malene E.; +178 more

Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue

Journal Article · 2024 · Nature Metabolism · OSTI ID:2446702

Many, Gina M.; Sanford, James A.; Sagendorf, Tyler J.; +109 more

A compendium of multi-omics data illuminating host responses to lethal human virus infections

Journal Article · 2024 · Scientific Data · OSTI ID:2335704

Eisfeld-Fenney, Amie J.; Anderson, Lindsey N.; Fan, Shufang; +26 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
epigenetics
metabolomics
proteomics
transcriptomics

Title: Temporal dynamics of the multi-omic response to endurance exercise training

Citation Formats

References (36)

Similar Records

Related Subjects