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Aerobic (AE) and resistance exercise (RE) elicit unique adaptations in skeletal muscle that have distinct implications for health and performance. The purpose of this study was to identify the unique transcriptome response of skeletal muscle to acute AE and RE. In a counterbalanced, crossover design, six healthy, recreationally active young men (27 ± 3 yr) completed acute AE (40 min of cycling, ∼70% maximal HR) and RE [8 sets, 10 reps, ∼65% 1-repetition maximum (1RM)], separated by ∼1 wk. Muscle biopsies (vastus lateralis) were obtained before and at 1 and 4 h postexercise. Whole transcriptome RNA sequencing (HiSeq2500; Illumina) was performed on cDNA synthesized from skeletal muscle RNA. Sequencing data were analyzed using HTSeq, and differential gene expression was identified using DESeq2 [adjusted P value (FDR)  1.5-fold change from preexercise]. RE resulted in a greater number of differentially expressed genes at 1 (67 vs. 48) and 4 h (523 vs. 221) compared with AE. We identified 348 genes that were differentially expressed only following RE, whereas 48 genes were differentially expressed only following AE. Gene clustering indicated that AE targeted functions related to zinc interaction, angiogenesis, and ubiquitination, whereas RE targeted functions related to transcription regulation, cytokine activity, cell adhesion, kinase activity, and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. ESRRG and TNFSRF12A were identified as potential targets related to the specific response of skeletal muscle to AE and RE, respectively. These data describe the early postexercise transcriptome response of skeletal muscle to acute AE and RE and further highlight that different forms of exercise stimulate unique molecular activity in skeletal muscle.    NEW &amp; NOTEWORTHY Whole transcriptome RNA sequencing was used to determine the early postexercise transcriptome response of skeletal muscle to acute aerobic (AE) and resistance exercise (RE) in untrained individuals. Although a number of shared genes were stimulated following both AE and RE, several genes were uniquely responsive to each exercise mode. These findings support the need for future research focused to better identify the role of exercise mode as it relates to targeting specific cellular skeletal muscle abnormalities.

Transcriptome response of human skeletal muscle to divergent exercise stimuli