{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:57:42Z","timestamp":1788973062523,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007129","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":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Declined skeletal muscle mass and function are inevitable consequences of long\u2010term diabetes and bring about many adverse events. Muscle fibre atrophy and interstitial fibrosis are major pathological manifestations of diabetic sarcopenia. Stimulator of interferon genes (STING) participates in various metabolic diseases. We aimed to explore whether and how STING regulates the above pathological manifestations of diabetic sarcopenia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Wild\u2010type and STING<jats:sup>gt\/gt<\/jats:sup> C57BL\/6J mice and C2C12 myotubes were used to study the role of STING in the regulation of diabetic sarcopenia and the underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>STING was abnormally activated in diabetic muscles and in PA\u2010treated myotubes (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01 for all parameters). The diabetic mice demonstrated decreased forelimb grip strength, lean mass, muscle weight and hanging impulse, which were improved by STING deficiency due to alleviated muscle fibre atrophy and interstitial fibrosis (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 for all parameters). STING deficiency alleviated muscle fibre atrophy through the following mechanisms. Firstly, STING deficiency or inhibition increased the contents of pDRP1<jats:sup>Ser616<\/jats:sup>, PINK1, Parkin and LC3\u2010II, decreased p62 content, and increased the amount of mito\u2010Keima fluorescent dots at 578\u00a0nm in diabetic state (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 for all parameters), suggesting improved mitofission and mitophagy. Secondly, STING deficiency or inhibition increased the expression of pAKT<jats:sup>Ser473<\/jats:sup> and GLUT4 post\u2010insulin change in diabetic state (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 for all), indicating alleviated insulin resistance (IR). Mechanically, STING deficiency or inhibition increased peroxisome proliferator activated receptors \u03b3 (PPAR\u03b3) protein content by reducing the degradation of ubiquitinated PPAR\u03b3 through the proteasome pathway and thus increased the expression of fatty acid oxidation (FAO)\u2010related proteins in diabetic state (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 for all parameters). Decreased expression of FAO\u2010related proteins caused by PPAR\u03b3 inhibition abolished the improvements in mitofission, mitophagy and IR achieved by STING inhibition in PA\u2010treated myotubes and thus promoted muscle fibre atrophy (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 for all parameters). STING deficiency alleviated interstitial fibrosis by decreasing TGF\u03b21 expression in diabetic state and TGF\u03b21 promoted the fibrogenic differentiation of fibro\u2010adipogenic progenitors (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 for all parameters). PPAR\u03b3 inhibition abolished the effect of STING inhibition on reducing TGF\u03b21 content in PA\u2010treated myotubes (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>STING deficiency exerted protective effects in diabetic sarcopenia by inhibiting the degradation of ubiquitinated PPAR\u03b3 through the proteasome pathway and enhancing PPAR\u03b3\u2010mediated FAO, which alleviated muscle fibre atrophy by promoting mitophagy and ameliorating IR, and alleviated interstitial fibrosis by reducing TGF\u03b21 production and suppressing the fibrogenic differentiation of fibro\u2010adipogenic progenitors.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13336","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T06:32:23Z","timestamp":1695364343000},"page":"2623-2641","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Stimulator of interferon genes promotes diabetic sarcopenia by targeting peroxisome proliferator activated receptors \u03b3 degradation and inhibiting fatty acid oxidation"],"prefix":"10.1002","volume":"14","author":[{"given":"Sen\u2010bo","family":"Yan","sequence":"first","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Liang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shandong Provincial Hospital Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zheng","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin\u2010xiao","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi\u2010jie","family":"Zheng","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui\u2010xia","family":"Lu","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo\u2010kai","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shandong Provincial Hospital 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