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

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

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

来源:bioRxiv_logobioRxiv
英文摘要

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

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

10.1101/2022.09.21.508770

基础医学生物科学研究方法、生物科学研究技术体育

Buford Thomas W.,Stowe Cynthia L.,Lindholm Malene E.,Nair Venugopalan D.,Schenk Simon,Lanza Ian R.,Zang Chongzhi,Miller Michael E.,Gritsenko Marina A.,Marwaha Shruti,Newgard Christopher,Piehowski Paul D.,Rooney Jessica L.,Sealfon Stuart C.,Smith Gregory R.,Smith Kevin S.,Steep Alec,Tracy Russell,Zhang Tiantian,Zhen Jimmy,Albertson Brent G.,Balci Ali Tugrul,Natarajan Raja Archana,Kachman Maureen T.,Keshishian Hasmik,Kraus William E.,Goodyear Laurie J.,Hutchinson-Bunch Chelsea,Jin Christopher A.,Nicklas Barbara,Radom-Aizik Shlomit,Ramachandran Krithika,Ramos Irene,Raskind Alexander (Sasha),Rejeski W. Jack,Richards Collyn,Rubenstein Aliza B.,Ruf-Zamojski Frederique,Rushing Scott,Sagendorf Tyler J.,Schwartz Robert,Ilkayeva Olga,Jimenez-Morales David,Bouverat Brian,Chikina Maria,Cicha Michael,Cornell Elaine,Farrar Roger,Hevener Andrea,Hsu Fang-Chi,Hershman Steven G.,Gadde Kishore,Guevara Kristy,Harris Melissa,Hastie Trevor,Hennig Krista M.,Kramer Kyle S.,Liu Xueyun,Lu Ching-ju,Mani DR,Marshall Andrea,May Sandy,Monroe Matthew E.,Moore Samuel,Newton Robert L. Jr.,Pearce Cadence,Petyuk Vladislav A.,Powers Scott,Jean Beltran Pierre M.,Adkins Joshua N.,Avila-Pacheco Julian,Bae Dam,Dennis Courtney,Evans Charles R.,Soni Tanu,Teng Christopher,Tibshirani Rob,Trappe Scott,Trappe Todd A.,Uppal Karan,Vangeti Sindhu,Vornholt Alexandria,Walkup Michael P.,Volpi Elena,Yan Zhen,Zaslavsky Elena,Zebarjadi Navid,Carr Steven,Snyder Michael P.,Wheeler Matthew T.,Ravussin Eric,Li Jun,Gaul David,Nachun Daniel,Chavez Clarisa,Lessard Sarah J.,Ramaker Megan E.,Nigro Pasquale,Moreau Kerrie L.,Bessesen Daniel,Goodpaster Bret H.,Booth Frank,Gerszten Robert,Almagro Armenteros Jose J.,Nestor Michael D.,Maner-Smith Kristal M.,Ashley Euan,Seenarine Nitish,Robbins Jeremy M.,Hansen Joshua R.,Johannsen Neil M.,Esser Karyn,Moore Ronald J.,Savage Evan,Marjanovic Nada,Walsh Martin J.,Presby David M.,Gagne Nicole,Amar David,Burant Charles,Huffman Kim M.,Ge Yongchao,Ke Benjamin G.,Rasmussen Blake B.,Hou Zhenxin,Jankowski Catherine,Hirshman Michael F.,Rirak Stas,Hung Chia-Jui,Makarewicz Nathan S.,Thyfault John,Nudelman German,Bararpour Nasim,Dasari Surendra,Thalacker-Mercer Anna,Melanson Edward,Lester Bridget,Qian Wei-Jun,Nair K. Sreekumaran,Wu Si,Chiu Roxanne,Sparks Lauren M.,Samdarshi Mihir,Lira Ana C.,Dalton Karen P.,Schauer Irene E.,Haddad Fadia,Williams John,Bergman Bryan,Muehlbauer Michael J.,Xia Ashley,Zhao Bingqing,MoTrPAC Study Group,De Sousa Luis Oliveria,Amper Mary Anne S.,Sanford James A.,Vasoya Mital,Jackson Bailey E.,Clish Clary,Rector R. Scott,Kohrt Wendy M.,Ivanova Anna A.,Bamman Marcas,Mundorff Charles C.,Bodine Sue C.,Pincas Hanna,Leeuwenburgh Christiaan,Rankinen Tuomo,Cutter Gary,Ortlund Eric A.,Cooper Dan,Vetr Nikolai G.,Gay Nicole R.,Coen Paul M.,Fern¨¢ndez Facundo M.,Pahor Marco,Montgomery Stephen B.,Barton Elisabeth R.,Many Gina M.,Yu Xuechen,Musi Nicolas,Caputo Tiziana,Sun Yifei,Chambers Toby L..Temporal dynamics of the multi-omic response to endurance exercise training across tissues[EB/OL].(2025-03-28)[2025-08-03].https://www.biorxiv.org/content/10.1101/2022.09.21.508770.点此复制

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