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Proteomic profiling on sex-specific changes on skeletal muscle after exercise

ABSTRACT: Biological sex-based differences are reported for aerobic capacity, exercise performance, skeletal muscle mass and fiber-type composition. We aimed to provide a yet missing comprehensive picture of molecular differences between female and male skeletal muscle before and during an 8-week exercise intervention. We characterized muscle biopsies from 25 (16f/9m) subjects with overweight and obesity in a multi-omics approach employing epigenomics, transcriptomics and proteomics at baseline, after acute exercise and after 8 weeks of supervised endurance training. Further we investigated which differences were conserved in myotubes obtained from these donors or can be restored by sex hormone treatment. We found differential CpG-site methylation in 16.012 genes, 1.366 differentially expressed genes and 120 differentially abundant proteins at baseline. Only non-autosomal gene expression was conserved in vitro. Part of sex-specific transcriptomic differences in vivo could be mimicked by sex hormone treatment in vitro. Differences in the proteome were dominated by higher abundance of proteins regulating glycogen degradation, glycolysis and of other fast-twitch fiber type proteins in males. Females showed higher abundance of proteins regulating fatty acid handling. The initial differences in fiber type-specific proteins were diminished after 8-week training, and both sexes adapted to endurance training by upregulating mitochondrial proteins involved in substrate oxidation and ATP production. Acute exercise upregulated stress-responsive transcripts predominantly in males. In conclusion, the sex-specific composition of the proteome underpins the differences in glucose and fatty acid metabolism in female and male skeletal muscle. Training mitigates these differences toward an endurance-trained proteomic profile in both sexes after only 8 weeks.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Skeletal Muscle, Myoblast Differentiation

SUBMITTER: Christine von Toerne

LAB HEAD: Cora Weigert

PROVIDER: PXD058700 | Pride | 2025-09-02

REPOSITORIES: Pride

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			Action	DRS
	WEC14046X002__M100_1_pre_resting_Input_92-274579.raw	Raw
	WEC14046X003__M100_2_pre_acuteexercise_Input_92-274580.raw	Raw
	WEC14046X004__M100_3_post_acuteexercise_Input_92-274581.raw	Raw
	WEC14046X005__M100_4_post_resting_Input_92-274582.raw	Raw
	WEC14046X008__M101_1_pre_resting_Input_92-274585.raw	Raw

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Project description:The molecular pathways which are activated and contribute to physiological remodeling of skeletal muscle in response to endurance exercise have not been fully characterized. We previously reported that ~800 gene transcripts are regulated following 6 weeks of supervised endurance training in young sedentary males, referred to as the training responsive transcriptome (TRT). Here we utilized this database together with data on biological variation in muscle adaptation to aerobic endurance training in both humans and a novel out-bred rodent model to study the potential regulatory molecules that coordinate this complex network of genes. We identified three DNA sequences representing RUNX1, SOX9, and PAX3 transcription factor binding sites as over-represented in the TRT. In turn, miRNA profiling indicated that several miRNAs targeting RUNX1, SOX9 and PAX3 were down-regulated by endurance training. The TRT was then examined by contrasting subjects who demonstrated the least vs. the greatest improvement in aerobic capacity (low vs. high responders), and at least 100 of the 800 TRT genes were differentially regulated, thus suggesting regulation of these genes may be important for improving aerobic capacity. In high responders, pro-angiogenic and tissue developmental networks emerged as key candidates for coordinating tissue aerobic adaptation. Beyond RNA level validation there were several DNA variants that associated with VO(2)max trainability in the HERITAGE Family Study but these did not pass conservative Bonferroni adjustment. In addition, in a rat model selected across 10 generations for high aerobic training responsiveness, we found that both the TRT and a homologous subset of the human high responder genes were regulated to a greater degree in high responder rodent skeletal muscle. This analysis provides a comprehensive map of the transcriptomic features important for aerobic exercise-induced improvements in maximal oxygen consumption. This data is from skeletal muscle post 6 weeks of endurance exercise training.

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Proteomic profiling on sex-specific changes on skeletal muscle after exercise

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