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The 24-Hour Time Course of Integrated Molecular Responses to Resistance Exercise in Human Skeletal Muscle Implicates MYC as a Hypertrophic Regulator

ABSTRACT: Molecular control of recovery after exercise in muscle is temporally dynamic. A time course of biopsies around resistance exercise (RE) combined with -omics is necessary to better comprehend the molecular choreography of skeletal muscle adaptation in humans. We collected vastus lateralis biopsies before and 30 minutes, 3-, 8-, and 24 hours after acute RE. RNA-sequencing defined the transcriptome and a time-point matched biopsy only group were controls. DNA methylomics and computational approaches complimented the transcriptome data. Moreover, we tested whether cyclic transient overexpression of transcription factor MYC for 4 weeks were sufficient to induce skeletal muscle hypertrophy in female mice.

ORGANISM(S): Homo sapiens

PROVIDER: GSE252357 | GEO | 2024/04/17

REPOSITORIES: GEO

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Project description:We sought to ascertain the time-course of transcriptional events that occur in human skeletal muscle at the outset of resistance exercise (RE) training in RE naïve individuals, and determine if the magnitude of any response was associated with exercise induced muscle damage. Sixteen RE naïve males were recruited, 8 underwent 2 sessions of 5x30 maximum, isokinetic knee extensions (180°.s-1) separated by 48 hrs. Muscle biopsies of the vastus lateralis were taken at baseline and 24 hrs after each exercise bout. Eight individuals acted as non-exercise controls with biopsies obtained at the same time intervals. Transcriptional changes were assessed by microarray, and binding of HSP27 and αB-crystallin to insoluble proteins by immunohistochemistry as a measure of muscle damage. In control subjects, no probesets were significantly altered (FDR<0.05) and HSP27 and αB-crystallin binding remained unchanged throughout the study. In exercised subjects, significant inter-subject variability following the initial bout of RE was observed in the muscle transcriptome, with greatest changes occurring when HSP27 and αB-crystallin binding was elevated. Following the second bout of RE, the transcriptome response was more consistent among subjects revealing a cohort of probesets associated with immune activation, the suppression of oxidative metabolism and protein ubiquitination as differentially regulated. The results reveal that the initial transcriptional response to RE is highly variable in RE naïve volunteers, is associated with muscle damage, and unlikely to reflect longer-term adaptations to RE training. These results highlight the importance of considering multiple time-points when determining the transcriptional response to RE and associated physiological adaptation. 16 healthy male subjects were recruited and attended the laboratory fasted on 4 consecutive days. Biopsies from the vastus lateralis muscle were obtained on Days 0, 1 and 3, with total RNA extracted for gene expression analysis by microarray. During this period, 8 subjects performed isokinetic leg extension exercise using an isokinetic dynamometer (180 degrees per second; maximum intensity) on two occassions (days 0 and 2). Data for 7 exercise subjects presented in this study. 8 further subjects acted as non-exercised controls and did not participate in any exercise during the study period. A number of technical replicates were included and are identified in the sample list. Insufficient muscle biopsy sample or inadequate RNA quality accounted for 8 missing data points (TechRep1 N=40 as opposed to 48).

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The 24-Hour Time Course of Integrated Molecular Responses to Resistance Exercise in Human Skeletal Muscle Implicates MYC as a Hypertrophic Regulator

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