A HIF-1 signature dominates the attenuation in the human skeletal muscle transcriptional response to high-intensity interval training

• Published in: Journal of applied physiology (1985) Vol. 132; no. 6; pp. 1448 - 1459
• Main Authors: Norrbom, Jessica Maria, Ydfors, Mia, Lovric, Alen, Perry, Christopher G R, Rundqvist, Helene, Rullman, Eric
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.06.2022
• Subjects: Adaptation; Attenuation; Biopsy; Cell adhesion; Complications; Gene regulation; Gene sequencing; Genes; Glycolysis; Growth factors; Heart rate; Interval training; MAP kinase; Medicin och hälsovetenskap; Muscles; Musculoskeletal system; Physical training; Skeletal muscle; Training; Transcription; Vascular endothelial growth factor; high-intensity interval training; exercise; skeletal muscle; human; transcriptome
• ISSN: 8750-7587; 1522-1601; 1522-1601
• DOI: 10.1152/japplphysiol.00310.2021

High-intensity interval training (HIIT) generates profound metabolic adaptations in skeletal muscle. These responses mirror performance improvements but follow a non-linear pattern comprised of an initial fast phase followed by a gradual plateau effect. The complete time-dependent molecular sequelae that regulates this plateau effect remains unknown. We hypothesize that the plateau effect during HIIT is restricted to specific pathways with communal upstream transcriptional regulation. To investigate this, eleven healthy men performed nine sessions of HIIT (10x4 minutes of cycling at 91 % of HR ) over a 3-week period. Before and 3h after the 1 and 9 exercise bout, skeletal muscle biopsies were obtained, and RNA sequencing performed. Almost 2,000 genes across 84 pathways were differentially expressed in response to a single HIIT session. The overall transcriptional response to acute exercise was strikingly similar at 3 weeks, 83 % (n=1650) of the genes regulated after the 1 bout of exercise were similarly regulated by the 9 bout, albeit with a smaller effect size, and the response attenuated to on average 70 % of the 1 bout. The attenuation differed substantially between pathways and was very pronounced for glycolysis and cellular adhesion but more preserved for MAPK and VEGF-A signalling. The attenuation was driven by a combination of changes in steady-state expression and specific transcriptional regulation. Given that the exercise intensity was progressively increased, and that the attenuation was pathway specific, we suggest that moderation of muscular adaptation after a period of training stems from targeted regulation rather than a diminished exercise stimulus.