Molecular adaptations in response to exercise training are associated with tissue-specific transcriptomic and epigenomic signatures

• DOI: 10.1016/j.xgen.2023.100421
• Publication Date: 2024-05-01T15:09:10Z
• Authors: Venugopalan D. Nair; Hanna Pincas; Gregory R. Smith; Elena Zaslavsky; Yongchao Ge; Mary Anne S. Amper; Mital Vasoya; Maria Chikina; Yifei Sun; Archana Natarajan...; Weiguang Mao; Nicole R. Gay; Karyn A. Esser; Kevin S. Smith; Bingqing Zhao; Laurens Wiel; Aditya Singh; Malene E. Lindholm; David Amar; Stephen Montgomery; Michael P. Snyder; Martin J. Walsh; Stuart C. Sealfon; Joshua N. Adkins; Jose Juan Almagro...; Euan Ashley; Dam Bae; Marcas Bamman; Nasim Bararpour; Alexis Bennett; Bryan C. Bergman; Daniel H. Bessesen; Sue C. Bodine; Thomas W. Buford; Toby L. Chambers; Clarisa Chavez; Tiffany Cortes; Gary Cutter; Sara Espinoza; Facundo M. Fernández; Nicole Gagne; David A. Gaul; Bret H. Goodpaster; Chia-Jui Hung; Bailey E. Jackson; Catherine M. Jank...; Christopher A. Jin; Wendy M. Kohrt; Kyle S. Kramer; Bridget Lester; Ana K. Lira; Sandy May; Nada Marjanovic; Edward L. Melanson; Samuel G. Moore; Kerrie L. Moreau; Nicolas Musi; Daniel Nachum; German Nudelman; Marco Pahor; Darpan Patel; Paul D. Piehowski; Wei-Jun Qian; Blake B. Rasmussen; Stas Rirak; Jessica L. Rooney; James A. Sanford; Evan M. Savage; Irene E. Schauer; Monica Serra; Cynthia L. Stowe; Anna Thalacker-Me...; Todd A. Trappe; Scott Trappe; Nikolai G. Vetr; Elena Volpi; Matthew T. Wheeler; Si Wu; Navid Zebarjadi; Jimmy Zhen
• Keywords: Male; Epigenomics; Rats, Sprague-Dawley; Organ Specificity; Physical Conditioning, Animal; Animals; Female; DNA Methylation; Transcriptome; Adaptation, Physiological; Article; Rats; Epigenesis, Genetic

Regular exercise has many physical and brain health benefits, yet the molecular mechanisms mediating exercise effects across tissues remain poorly understood. Here we analyzed 400 high-quality DNA methylation, ATAC-seq, and RNA-seq datasets from eight tissues from control and endurance exercise-trained (EET) rats. Integration of baseline datasets mapped the gene location dependence of epigenetic control features and identified differing regulatory landscapes in each tissue. The transcriptional responses to 8 weeks of EET showed little overlap across tissues and predominantly comprised tissue-type enriched genes. We identified sex differences in the transcriptomic and epigenomic changes induced by EET. However, the sex-biased gene responses were linked to shared signaling pathways. We found that many G protein-coupled receptor-encoding genes are regulated by EET, suggesting a role for these receptors in mediating the molecular adaptations to training across tissues. Our findings provide new insights into the mechanisms underlying EET-induced health benefits across organs.