Dynamic transcriptomic responses to divergent acute exercise stimuli in young adults.
Kaleen M Lavin, Zachary A Graham, Jeremy S McAdam, Samia M O'Bryan, Devin Drummer, Margaret B Bell, Christian J Kelley, Manoel E Lixandrão, Brandon Peoples, S Craig Tuggle, Regina S Seay, Kendall Van Keuren-Jensen, Matthew J Huentelman, Patrick Pirrotte, Rebecca Reiman, Eric Alsop, Elizabeth Hutchins, Jerry Antone, Anna Bonfitto, Bessie Meechoovet, Joanna Palade, Joshua S Talboom, Amber Sullivan, Inmaculada Aban, Kalyani Peri, Timothy J Broderick, Marcas M Bamman
Author Information
Kaleen M Lavin: Healthspan, Resilience, and Performance, Florida Institute for Human and Machine Cognition, Pensacola, Florida, United States. ORCID
Zachary A Graham: Healthspan, Resilience, and Performance, Florida Institute for Human and Machine Cognition, Pensacola, Florida, United States.
Jeremy S McAdam: Healthspan, Resilience, and Performance, Florida Institute for Human and Machine Cognition, Pensacola, Florida, United States.
Samia M O'Bryan: UAB Center for Exercise Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, United States.
Devin Drummer: UAB Center for Exercise Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, United States. ORCID
Margaret B Bell: UAB Center for Exercise Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, United States.
Christian J Kelley: UAB Center for Exercise Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, United States.
Manoel E Lixandrão: UAB Center for Exercise Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, United States.
Brandon Peoples: UAB Center for Exercise Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, United States.
S Craig Tuggle: Healthspan, Resilience, and Performance, Florida Institute for Human and Machine Cognition, Pensacola, Florida, United States.
Regina S Seay: UAB Center for Exercise Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, United States.
Kendall Van Keuren-Jensen: Cancer & Cell Biology, Translational Genomics Research Institute, Phoenix, Arizona, United States.
Matthew J Huentelman: Cancer & Cell Biology, Translational Genomics Research Institute, Phoenix, Arizona, United States.
Patrick Pirrotte: Cancer & Cell Biology, Translational Genomics Research Institute, Phoenix, Arizona, United States.
Rebecca Reiman: Cancer & Cell Biology, Translational Genomics Research Institute, Phoenix, Arizona, United States.
Eric Alsop: Cancer & Cell Biology, Translational Genomics Research Institute, Phoenix, Arizona, United States.
Elizabeth Hutchins: Cancer & Cell Biology, Translational Genomics Research Institute, Phoenix, Arizona, United States.
Jerry Antone: Cancer & Cell Biology, Translational Genomics Research Institute, Phoenix, Arizona, United States.
Anna Bonfitto: Cancer & Cell Biology, Translational Genomics Research Institute, Phoenix, Arizona, United States.
Bessie Meechoovet: Cancer & Cell Biology, Translational Genomics Research Institute, Phoenix, Arizona, United States.
Joanna Palade: Cancer & Cell Biology, Translational Genomics Research Institute, Phoenix, Arizona, United States.
Joshua S Talboom: Cancer & Cell Biology, Translational Genomics Research Institute, Phoenix, Arizona, United States.
Amber Sullivan: UAB Center for Exercise Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, United States.
Inmaculada Aban: Department of Biostatistics, The University of Alabama at Birmingham, Birmingham, Alabama, United States.
Kalyani Peri: Department of Biostatistics, The University of Alabama at Birmingham, Birmingham, Alabama, United States.
Timothy J Broderick: Healthspan, Resilience, and Performance, Florida Institute for Human and Machine Cognition, Pensacola, Florida, United States.
Marcas M Bamman: Healthspan, Resilience, and Performance, Florida Institute for Human and Machine Cognition, Pensacola, Florida, United States. ORCID
Acute exercise elicits dynamic transcriptional changes that, when repeated, form the fundamental basis of health, resilience, and performance adaptations. While moderate-intensity endurance training combined with conventional resistance training (traditional, TRAD) is often prescribed and recommended by public health guidance, high-intensity training combining maximal-effort intervals with intensive, limited-rest resistance training is a time-efficient alternative that may be used tactically (HITT) to confer similar benefits. Mechanisms of action of these distinct stimuli are incompletely characterized and have not been directly compared. We assessed transcriptome-wide responses in skeletal muscle and circulating extracellular vesicles (EVs) to a single exercise bout in young adults randomized to TRAD ( = 21, 12 M/9 F, 22 ± 3 yr) or HITT ( = 19, 11 M/8 F, 22 ± 2 yr). Next-generation sequencing captured small, long, and circular RNA in muscle and EVs. Analysis identified differentially expressed transcripts (|logFC|>1, FDR ≤ 0.05) immediately (h0, EVs only), h3, and h24 postexercise within and between exercise protocols. In aaddition, all apparently responsive transcripts (FDR < 0.2) underwent singular value decomposition to summarize data structures into latent variables (LVs) to deconvolve molecular expression circuits and interregulatory relationships. LVs were compared across time and exercise protocol. TRAD, a longer but less intense stimulus, generally elicited a stronger transcriptional response than HITT, but considerable overlap and key differences existed. Findings reveal shared and unique molecular responses to the exercise stimuli and lay groundwork toward establishing relationships between protein-coding genes and lesser-understood transcripts that serve regulatory roles following exercise. Future work should advance the understanding of these circuits and whether they repeat in other populations or following other types of exercise/stress. We examined small and long transcriptomics in skeletal muscle and serum-derived extracellular vesicles before and after a single exposure to traditional combined exercise (TRAD) and high-intensity tactical training (HITT). Across 40 young adults, we found more consistent protein-coding gene responses to TRAD, whereas HITT elicited differential expression of microRNA enriched in brain regions. Follow-up analysis revealed relationships and temporal dynamics across transcript networks, highlighting potential avenues for research into mechanisms of exercise response and adaptation.
