Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue
Authors: Many Gina M. , Sanford James A. , Sagendorf Tyler J. , Hou Zhenxin , Nigro Pasquale , Whytock Katie L. , Amar David , Caputo Tiziana , Gay Nicole R. , Gaul David A. , Hirshman Michael F. , Jimenez-Morales David , Lindholm Malene E. , Muehlbauer Michael J. , Vamvini Maria , Bergman Bryan C. , Fernández Facundo M. , Goodyear Laurie J. , Hevener Andrea L. , Ortlund Eric A. , Sparks Lauren M. , Xia Ashley , Adkins Joshua N. , Bodine Sue C. , Newgard Christopher B. , Schenk Simon ,   The MoTrPAC Study Group, Armenteros Jose Juan Almagro , Amper Mary Anne S. , Ashley Euan , Asokan Aneesh Kumar , Avila-Pacheco Julian , Bae Dam , Bamman Marcas M. , Bararpour Nasim , Barnes Jerry , Buford Thomas W. , Burant Charles F. , Carbone Nicholas P. , Carr Steven A. , Chambers Toby L. , Chavez Clarisa , Chiu Roxanne , Clish Clary B. , Cutter Gary R. , Dasari Surendra , Dennis Courtney , Evans Charles R. , Fernandez Facundo M. , Gagne Nicole , Ge Yongchao , Goodpaster Bret H. , Gritsenko Marina A. , Hansen Joshua R. , Hennig Krista M. , Huffman Kim M. , Hung Chia-Jui , Hutchinson-Bunch Chelsea , Ilkayeva Olga , Ivanova Anna A. , Beltran Pierre M. Jean , Jin Christopher A. , Kachman Maureen T. , Keshishian Hasmik , Kraus William E. , Lanza Ian , Lester Bridget , Li Jun Z. , Lira Ana K. , Liu Xueyun , Maner-Smith Kristal M. , May Sandy , Monroe Matthew R. , Montgomery Stephen , Moore Ronald J. , Moore Samuel G. , Nachun Daniel , Nair K. Sreekumaran , Nair Venugopalan , Raja Archana Natarajan , Nestor Michael D. , Nudelman German , Petyuk Vladislav A. , Piehowski Paul D. , Pincas Hanna , Qian Wei-Jun , Raskind Alexander , Rasmussen Blake B. , Rooney Jessica L. , Rushing Scott , Samdarshi Mihir , Sealfon Stuart C. , Smith Kevin S. , Smith Gregory R. , Snyder Michael , Stowe Cynthia L. , Talton Jennifer W. , Teng Christopher , Thalacker-Mercer Anna , Tracy Russell , Trappe Todd A. , Vasoya Mital , Vetr Nikolai G. , Volpi Elena , Walkup Michael P. , Walsh Martin J. , Wheeler Matthew T. , Wu Si , Zaslavsky Elena , Zebarjadi Navid , Zhang Tiantian , Zhao Bingqing , Zhen Jimmy 
Published: May 2024

Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training (ExT) and sex on its molecular landscape is not fully established. Utilizing an integrative multi-omics approach, and leveraging data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we show profound sexual dimorphism in the scWAT of sedentary rats and in the dynamic response of this tissue to ExT. Specifically, the scWAT of sedentary females displays -omic signatures related to insulin signaling and adipogenesis, whereas the scWAT of sedentary males is enriched in terms related to aerobic metabolism. These sex-specific -omic signatures are preserved or amplified with ExT. Integration of multi-omic analyses with phenotypic measures identifies molecular hubs predicted to drive sexually distinct responses to training. Overall, this study underscores the powerful impact of sex on adipose tissue biology and provides a rich resource to investigate the scWAT response to ExT.