Simon I. Dreher , Thomas Goj , Christine von Toerne , Miriam Hoene , Martin Irmler , Meriem Ouni , Markus Jähnert , Johannes Beckers , Martin Hrabě de Angelis , Andreas Peter , Anja Moller , Andreas L. Birkenfeld , Annette Schürmann , Stefanie M. Hauck , Cora Weigert
{"title":"静止骨骼肌的性别差异以及超重和肥胖个体对耐力运动的急性和长期反应。","authors":"Simon I. Dreher , Thomas Goj , Christine von Toerne , Miriam Hoene , Martin Irmler , Meriem Ouni , Markus Jähnert , Johannes Beckers , Martin Hrabě de Angelis , Andreas Peter , Anja Moller , Andreas L. Birkenfeld , Annette Schürmann , Stefanie M. Hauck , Cora Weigert","doi":"10.1016/j.molmet.2025.102185","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><div>Endurance exercise reduces the risk of metabolic diseases by improving skeletal muscle metabolism, particularly in individuals with overweight and obesity. As biological sex impacts glucose and fatty acid handling in skeletal muscle, we hypothesized sex differences at the transcriptomic and proteomic level in the acute response to exercise and after an 8-week exercise intervention.</div></div><div><h3>Methods</h3><div>We analyzed skeletal muscle biopsies from 25 sedentary subjects (16f/9 m) with overweight and obesity using transcriptomics and proteomics at baseline, after acute exercise, and following an 8-week endurance training program. Regulation of sex-specific differences was studied in primary myotubes from the donors.</div></div><div><h3>Results</h3><div>At baseline, differentially methylated CpG-sites potentially explain up to 59% of transcriptomic and 67% of proteomic sex differences. Differences were dominated by higher abundance of fast-twitch fiber type proteins, and transcripts and proteins regulating glycogen degradation and glycolysis in males. Females showed higher abundance of proteins regulating fatty acid uptake and storage. Acute exercise induced stress-responsive transcripts and serum myoglobin predominantly in males. Both sexes adapted to 8-week endurance training by upregulating mitochondrial proteins involved in TCA cycle, oxidative phosphorylation, and β-oxidation. Training equalized fast-twitch fiber type protein levels, mainly by reducing them in males. In vivo sex differences in autosomal genes were poorly retained in myotubes but partially restored by sex hormone treatment.</div></div><div><h3>Conclusions</h3><div>Our findings highlight sex-specific molecular signatures that reflect known differences in glucose and lipid metabolism between female and male skeletal muscle. After just 8 weeks of endurance training, these sex differences were attenuated, suggesting a convergence towards a shared beneficial adaptation at the molecular level.</div></div>","PeriodicalId":18765,"journal":{"name":"Molecular Metabolism","volume":"98 ","pages":"Article 102185"},"PeriodicalIF":6.6000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sex differences in resting skeletal muscle and the acute and long-term response to endurance exercise in individuals with overweight and obesity\",\"authors\":\"Simon I. Dreher , Thomas Goj , Christine von Toerne , Miriam Hoene , Martin Irmler , Meriem Ouni , Markus Jähnert , Johannes Beckers , Martin Hrabě de Angelis , Andreas Peter , Anja Moller , Andreas L. Birkenfeld , Annette Schürmann , Stefanie M. Hauck , Cora Weigert\",\"doi\":\"10.1016/j.molmet.2025.102185\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objectives</h3><div>Endurance exercise reduces the risk of metabolic diseases by improving skeletal muscle metabolism, particularly in individuals with overweight and obesity. As biological sex impacts glucose and fatty acid handling in skeletal muscle, we hypothesized sex differences at the transcriptomic and proteomic level in the acute response to exercise and after an 8-week exercise intervention.</div></div><div><h3>Methods</h3><div>We analyzed skeletal muscle biopsies from 25 sedentary subjects (16f/9 m) with overweight and obesity using transcriptomics and proteomics at baseline, after acute exercise, and following an 8-week endurance training program. Regulation of sex-specific differences was studied in primary myotubes from the donors.</div></div><div><h3>Results</h3><div>At baseline, differentially methylated CpG-sites potentially explain up to 59% of transcriptomic and 67% of proteomic sex differences. Differences were dominated by higher abundance of fast-twitch fiber type proteins, and transcripts and proteins regulating glycogen degradation and glycolysis in males. Females showed higher abundance of proteins regulating fatty acid uptake and storage. Acute exercise induced stress-responsive transcripts and serum myoglobin predominantly in males. Both sexes adapted to 8-week endurance training by upregulating mitochondrial proteins involved in TCA cycle, oxidative phosphorylation, and β-oxidation. Training equalized fast-twitch fiber type protein levels, mainly by reducing them in males. In vivo sex differences in autosomal genes were poorly retained in myotubes but partially restored by sex hormone treatment.</div></div><div><h3>Conclusions</h3><div>Our findings highlight sex-specific molecular signatures that reflect known differences in glucose and lipid metabolism between female and male skeletal muscle. After just 8 weeks of endurance training, these sex differences were attenuated, suggesting a convergence towards a shared beneficial adaptation at the molecular level.</div></div>\",\"PeriodicalId\":18765,\"journal\":{\"name\":\"Molecular Metabolism\",\"volume\":\"98 \",\"pages\":\"Article 102185\"},\"PeriodicalIF\":6.6000,\"publicationDate\":\"2025-06-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Metabolism\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2212877825000924\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Metabolism","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2212877825000924","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Sex differences in resting skeletal muscle and the acute and long-term response to endurance exercise in individuals with overweight and obesity
Objectives
Endurance exercise reduces the risk of metabolic diseases by improving skeletal muscle metabolism, particularly in individuals with overweight and obesity. As biological sex impacts glucose and fatty acid handling in skeletal muscle, we hypothesized sex differences at the transcriptomic and proteomic level in the acute response to exercise and after an 8-week exercise intervention.
Methods
We analyzed skeletal muscle biopsies from 25 sedentary subjects (16f/9 m) with overweight and obesity using transcriptomics and proteomics at baseline, after acute exercise, and following an 8-week endurance training program. Regulation of sex-specific differences was studied in primary myotubes from the donors.
Results
At baseline, differentially methylated CpG-sites potentially explain up to 59% of transcriptomic and 67% of proteomic sex differences. Differences were dominated by higher abundance of fast-twitch fiber type proteins, and transcripts and proteins regulating glycogen degradation and glycolysis in males. Females showed higher abundance of proteins regulating fatty acid uptake and storage. Acute exercise induced stress-responsive transcripts and serum myoglobin predominantly in males. Both sexes adapted to 8-week endurance training by upregulating mitochondrial proteins involved in TCA cycle, oxidative phosphorylation, and β-oxidation. Training equalized fast-twitch fiber type protein levels, mainly by reducing them in males. In vivo sex differences in autosomal genes were poorly retained in myotubes but partially restored by sex hormone treatment.
Conclusions
Our findings highlight sex-specific molecular signatures that reflect known differences in glucose and lipid metabolism between female and male skeletal muscle. After just 8 weeks of endurance training, these sex differences were attenuated, suggesting a convergence towards a shared beneficial adaptation at the molecular level.
期刊介绍:
Molecular Metabolism is a leading journal dedicated to sharing groundbreaking discoveries in the field of energy homeostasis and the underlying factors of metabolic disorders. These disorders include obesity, diabetes, cardiovascular disease, and cancer. Our journal focuses on publishing research driven by hypotheses and conducted to the highest standards, aiming to provide a mechanistic understanding of energy homeostasis-related behavior, physiology, and dysfunction.
We promote interdisciplinary science, covering a broad range of approaches from molecules to humans throughout the lifespan. Our goal is to contribute to transformative research in metabolism, which has the potential to revolutionize the field. By enabling progress in the prognosis, prevention, and ultimately the cure of metabolic disorders and their long-term complications, our journal seeks to better the future of health and well-being.