{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:35:59Z","timestamp":1789133759388,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:00:00Z","timestamp":1735171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:00:00Z","timestamp":1735171200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170575"],"award-info":[{"award-number":["82170575"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370900"],"award-info":[{"award-number":["82370900"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Skeletal muscle remodelling can cause clinically important changes in muscle phenotypes. Satellite cells (SCs) myogenic potential underlies the maintenance of muscle plasticity. Accumulating evidence shows the importance of succinate in muscle metabolism and function. However, whether succinate can affect SC function and subsequently coordinate muscle remodelling to exercise remains unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A mouse model of high\u2010intensity interval training (HIIT) was used to investigate the effects of succinate on muscle remodelling and SC function by exercise capacity test and biochemical methods. Mice with succinate receptor 1 (SUCNR1)\u2010specific knockout in SCs were generated as an in\u00a0vivo model to explore the underlying mechanisms. RNA sequencing of isolated SCs was performed to identify molecular changes responding to succinate\u2010SUCNR1 signalling. The effects of identified key molecules on the myogenic capacity of SCs were investigated using gain\u2010 and loss\u2010of\u2010function assays in\u00a0vitro. To support the translational application, the clinical efficacy of succinate was explored in muscle\u2010wasting mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After 21\u2009days of HIIT, mice supplemented with 1.5% succinate exhibited striking gains in grip strength (+0.38\u2009\u00b1\u20090.04 vs. 0.26\u2009\u00b1\u20090.03\u2009N,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and endurance (+276.70\u2009\u00b1\u200955.80 vs. 201.70\u2009\u00b1\u200945.31\u2009s,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), accompanied by enhanced muscle hypertrophy and neuromuscular junction regeneration (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). The myogenic capacity of SCs was significantly increased in gastrocnemius muscle of mice supplemented with 1% and 1.5% succinate (+16.48% vs. control,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.008; +47.25% vs. control,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001, respectively). SUCNR1\u2010specific deletion in SCs abolished the modulatory influence of succinate on muscle adaptation in response to exercise, revealing that SCs respond to succinate\u2013SUCNR1 signalling, thereby facilitating muscle remodelling. SUCNR1 signalling markedly upregulated genes associated with stem cell differentiation and phosphorylation pathways within SCs, of which p38\u03b1 mitogen\u2010activated protein kinase (MAPK; fold change\u2009=\u20096.7,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and protein kinase C eta (PKC\u03b7; fold change\u2009=\u200912.5,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) expressions were the most enriched, respectively. Mechanistically, succinate enhanced the myogenic capacity of isolated SCs by activating the SUCNR1\u2013PKC\u03b7\u2013p38\u03b1 MAPK pathway. Finally, succinate promoted SC differentiation (1.5\u2010fold,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), ameliorating dexamethasone\u2010induced muscle atrophy in mice (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings reveal a novel function of succinate in enhancing SC myogenic capacity via SUCNR1, leading to enhanced muscle adaptation in response to exercise. These findings provide new insights for developing pharmacological strategies to overcome muscle atrophy\u2013related diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13670","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T07:32:37Z","timestamp":1735198357000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Succinate Regulates Exercise\u2010Induced Muscle Remodelling by Boosting Satellite Cell Differentiation Through Succinate Receptor 1"],"prefix":"10.1002","volume":"16","author":[{"given":"Yifan","family":"Shi","sequence":"first","affiliation":[{"name":"Clinical Nutrition Service Center, Department of General Surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing Jiangsu China"},{"name":"Department of Gastrointestinal Surgery Affiliated Hospital of Jiangnan University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Zhou","sequence":"additional","affiliation":[{"name":"Clinical Nutrition Service Center, Department of General Surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Nutrition Service Center, Department of General Surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longchang","family":"Huang","sequence":"additional","affiliation":[{"name":"Clinical Nutrition Service Center, Department of General Surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing Jiangsu 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