{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:03:10Z","timestamp":1791568990412,"version":"4.3.4"},"reference-count":36,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Graduate Student Research Innovation Program in Shanxi Province","award":["2024KY311"],"award-info":[{"award-number":["2024KY311"]}]},{"name":"Fundamental Research Program of Shanxi Province Graduate Education Innovation Programme","award":["2024TD14"],"award-info":[{"award-number":["2024TD14"]}]},{"name":"Fund for the Fundamental Research Program of Shanxi Province","award":["202303021211092"],"award-info":[{"award-number":["202303021211092"]}]},{"name":"Shanxi Agricultural University Science and Technology Innovation Enhancement Project","award":["CXGC2023017"],"award-info":[{"award-number":["CXGC2023017"]}]},{"name":"Shanxi Veterinary Pharmaceutical Industry Technology Innovation Research Institute","award":["2024CXYRH-042"],"award-info":[{"award-number":["2024CXYRH-042"]}]},{"name":"Shanxi Veterinary Pharmaceutical Industry Technology Innovation Strategic Alliance","award":["2024CXYRH-046"],"award-info":[{"award-number":["2024CXYRH-046"]}]},{"name":"Young Science & Technology Leadership Program","award":["2024YQPYGC02"],"award-info":[{"award-number":["2024YQPYGC02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Sarcopenia, characterized by progressive skeletal muscle mass, strength, and functional loss, imposes a substantial global health burden. Irisin, a myokine derived from fibronectin type III domain-containing protein 5 (FNDC5), is critical for muscle health. Here, we investigate its role in mitigating glucocorticoid-induced sarcopenia using a mouse and C2C12 myotubes model. We quantified FNDC5\/irisin levels in skeletal muscle and plasma and assessed muscle function (body weight, grip strength, wire-hanging, and locomotor activity), histology, and mitochondrial features following irisin administration to dexamethasone-treated mice. Western blot analyzed synthesis\/hydrolysis regulators, apoptosis markers, and mitochondrial regulators in mouse muscle tissues and C2C12 myotubes. The results show that FNDC5\/irisin was significantly downregulated in sarcopenic mice and atrophic C2C12 myotubes; exogenous irisin rescued muscle mass loss and functional impairment, improving body weight, muscle mass, grip strength, and mobility. Mechanistically, irisin bound SIRT1 with \u221212.7 kcal\/mol affinity, activating a deacetylation cascade that suppressed FoxO3a transcriptional activity (attenuating proteasomal degradation) and enhanced mTORC1-mediated protein synthesis in C2C12 myotubes. Additionally, irisin potentiated PGC-1\u03b1 signaling in mouse myocytes, promoting mitochondrial biogenesis and restoring contractile function in dystrophic fibers. Collectively, these findings demonstrate irisin alleviates glucocorticoid-induced muscle atrophy via SIRT1-dependent pathways, rebalancing muscle physiology and systemic energy homeostasis. This highlights irisin-based therapeutics as a promising exercise surrogate for sarcopenia management, offering novel clinical avenues.<\/jats:p>","DOI":"10.3390\/cells14211675","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T11:47:19Z","timestamp":1761652039000},"page":"1675","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Irisin Increases Sirtuin 1 to Improve Glucocorticoid-Induced Sarcopenia and Mitochondrial Dysfunction"],"prefix":"10.3390","volume":"14","author":[{"given":"Hongwei","family":"Shi","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Sun","sequence":"additional","affiliation":[{"name":"Shanghai General Hosptial, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuepeng","family":"Fan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Xie","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Hao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simiao","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7315-0729","authenticated-orcid":false,"given":"Jiayin","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomao","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjun","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6907-7172","authenticated-orcid":false,"given":"Haidong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai General Hosptial, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1007\/s00125-020-05177-6","article-title":"Exercise and metabolic health: Beyond skeletal muscle","volume":"63","author":"Thyfault","year":"2020","journal-title":"Diabetologia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/nrd4467","article-title":"Muscle wasting in disease: Molecular mechanisms and promising therapies","volume":"14","author":"Cohen","year":"2014","journal-title":"Nat. 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