Sex differences in muscle protein expression and DNA methylation in response to exercise training

Biology of Sex Differences

Research

Lyn R. Griffiths¹  Larisa M. Haupt¹  Kevin J. Ashton²  Nicholas R. Harvey³  Macsue Jacques⁴  Javier Alvarez-Romero⁴  Nir Eynon⁵  Shanie Landen⁶  Danielle Hiam⁷  Sarah Voisin⁸  Séverine Lamon⁹  Cheng Huang^1,10  Ralf B. Schittenhelm^1,10  Anup D. Shah^1,10  Joel R. Steele^1,10 

[1] Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Queensland University of Technology (QUT), 60 Musk Ave., 4059, Kelvin Grove, QLD, Australia;Faculty of Health Sciences and Medicine, Bond University, 4226, Gold Coast, QLD, Australia;Faculty of Health Sciences and Medicine, Bond University, 4226, Gold Coast, QLD, Australia;Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Queensland University of Technology (QUT), 60 Musk Ave., 4059, Kelvin Grove, QLD, Australia;Institute for Health and Sport (iHeS), Victoria University, Melbourne, Australia;Institute for Health and Sport (iHeS), Victoria University, Melbourne, Australia;Australian Regenerative Medicine Institute (ARMI), Monash University, 3800, Clayton, VIC, Australia;Institute for Health and Sport (iHeS), Victoria University, Melbourne, Australia;Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Melbourne, VIC, Australia;Institute for Health and Sport (iHeS), Victoria University, Melbourne, Australia;Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia;Institute for Health and Sport (iHeS), Victoria University, Melbourne, Australia;Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia;Monash Proteomics and Metabolomics Facility, Monash University, Melbourne, Australia;

关键词: Sex differences;    Skeletal muscle;    Proteome;    DNA methylation;    Epigenetics;    Exercise;   

DOI  :  10.1186/s13293-023-00539-2

 received in 2023-01-05, accepted in 2023-08-18,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundExercise training elicits changes in muscle physiology, epigenomics, transcriptomics, and proteomics, with males and females exhibiting differing physiological responses to exercise training. However, the molecular mechanisms contributing to the differing adaptations between the sexes are poorly understood.MethodsWe performed a meta-analysis for sex differences in skeletal muscle DNA methylation following an endurance training intervention (Gene SMART cohort and E-MTAB-11282 cohort). We investigated for sex differences in the skeletal muscle proteome following an endurance training intervention (Gene SMART cohort). Lastly, we investigated whether the methylome and proteome are associated with baseline cardiorespiratory fitness (maximal oxygen consumption; VO2max) in a sex-specific manner.ResultsHere, we investigated for the first time, DNA methylome and proteome sex differences in response to exercise training in human skeletal muscle (n = 78; 50 males, 28 females). We identified 92 DNA methylation sites (CpGs) associated with exercise training; however, no CpGs changed in a sex-dependent manner. In contrast, we identified 189 proteins that are differentially expressed between the sexes following training, with 82 proteins differentially expressed between the sexes at baseline. Proteins showing the most robust sex-specific response to exercise include SIRT3, MRPL41, and MBP. Irrespective of sex, cardiorespiratory fitness was associated with robust methylome changes (19,257 CpGs) and no proteomic changes. We did not observe sex differences in the association between cardiorespiratory fitness and the DNA methylome. Integrative multi-omic analysis identified sex-specific mitochondrial metabolism pathways associated with exercise responses. Lastly, exercise training and cardiorespiratory fitness shifted the DNA methylomes to be more similar between the sexes.ConclusionsWe identified sex differences in protein expression changes, but not DNA methylation changes, following an endurance exercise training intervention; whereas we identified no sex differences in the DNA methylome or proteome response to lifelong training. Given the delicate interaction between sex and training as well as the limitations of the current study, more studies are required to elucidate whether there is a sex-specific training effect on the DNA methylome. We found that genes involved in mitochondrial metabolism pathways are differentially modulated between the sexes following endurance exercise training. These results shed light on sex differences in molecular adaptations to exercise training in skeletal muscle.

【 授权许可】

CC BY   
© Society for Women's Health Research and BioMed Central Ltd. 2023

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