Multidimensional biocircuitry of exercise adaptation: integrating in vivo and ex vivo phenomics with miRNA mapping

In a randomized, dose-response trial, we used molecular and phenomic profiling to compare responses with traditional moderate-intensity endurance and resistance training (TRAD) versus high-intensity tactical training (HITT) that encompassed explosive whole-body interval training and high-intensity resistance training. Ninety-four participants (18-27 yr) completed 12 wk of TRAD or HITT followed by 4 wk of detraining. Although similar performance and body composition improvements were observed in response to HITT and TRAD, some dose-dependent differences were observed for: <i>1</i>) ex vivo muscle tissue changes in myofiber size, capillarization, satellite cell frequency, and mitochondrial function and <i>2</i>) differential gene expression (DGE) of muscle and serum exosomal miRNAs (miRs). However, these dose-dependent ex vivo muscle adaptations were overshadowed by wide-ranging interindividual response heterogeneity (IRH). We therefore explored response heterogeneity by first establishing minimum clinically important difference (MCID) scores to classify each participant based on MCIDs for functional muscle quality (fMQ) and cardiorespiratory fitness (CRF) and then modeling all data based on MCID classification. Using higher-order singular value decomposition (HOSVD), we established multidimensional biocircuitry linked to interindividual response heterogeneity that identified the most influential features across lifestyle, body composition, performance, ex vivo muscle tissue, and miRNA mapping domains. Via cross-comparison of MCID-linked miRs identified via DGE and HOSVD, nine miRs emerged as robust features of training adaptability, providing new insights into the integrated biocircuitry driving IRH.<b>NEW & NOTEWORTHY</b> We examined in vivo and ex vivo adaptations to traditional moderate-intensity endurance and resistance training (TRAD) versus high-intensity tactical training (HITT; explosive whole-body interval training and high-intensity resistance training). TRAD and HITT improved physiological performance and body composition, and induced ex vivo muscle adaptations, with remarkable interindividual response heterogeneity (IRH) in improvements. We leveraged multidimensional modeling to identify interindividual response heterogeneity biocircuitry that integrates deep phenotyping and miR transcriptomics (serum exosomes and skeletal muscle).