{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:20:10Z","timestamp":1787746810191,"version":"build-2784847793"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sarcopenia is a major contributor to frailty and mortality in ageing and obesity and is tightly linked to metabolic dysfunction. Imeglimin is a first\u2010in\u2010class oral hypoglycaemic agent targeting mitochondrial function; however, despite the central role of mitochondria in skeletal muscle homeostasis, its effects on skeletal muscle under sarcopenia\u2010relevant conditions remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Imeglimin was administered to male C57BL\/6 mice with high\u2010fat diet (HFD)\u2013induced obesity for 6\u2009weeks and to naturally aged (18\u2009months old) male mice for 12\u2009weeks. Skeletal muscle fibre morphology and transcriptomic profiles were analysed in fast\u2010 and slow\u2010twitch muscles. In parallel, C2C12 myotubes were exposed to palmitate with or without imeglimin, and inflammatory gene expression and reactive oxygen species (ROS) generation were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Imeglimin significantly increased the cross\u2010sectional area (CSA) of Type II fibres in the extensor digitorum longus (EDL) muscle of HFD\u2010fed mice (+66%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01 vs. controls). Transcriptomic analyses revealed suppression of conserved molecular signatures of muscle atrophy, including activation of immediate\u2010early genes and inflammatory pathways (\u221262% to \u221279%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05 vs. HFD\u2010fed mice). In palmitate\u2010treated C2C12 myotubes, imeglimin attenuated lipotoxicity\u2010induced inflammatory gene expression (\u221228% to \u221272%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05 vs. controls) with reduced ROS generation, consistent with its cell\u2010autonomous effect on myocytes. Notably, in naturally aged mice, 12\u2010week imeglimin treatment preserved EDL muscle fibre size (+14%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05 vs. controls) without altering systemic glucose tolerance, accompanied by transcriptomic changes overlapping with those observed in the HFD model (\u221227% to \u221282%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05 vs. aged controls).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Imeglimin attenuates skeletal muscle atrophy in obesity and ageing, accompanied by coordinated suppression of stress\u2010 and inflammation\u2010associated transcriptional programmes. These findings indicate that pharmacological regulation of mitochondrial stress responses influences skeletal muscle vulnerability under chronic metabolic stress and identify skeletal muscle as a previously underappreciated target of imeglimin action.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70354","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:52:41Z","timestamp":1785307961000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Imeglimin Attenuates Skeletal Muscle Atrophy in Mouse Models of Obesity and Ageing"],"prefix":"10.1002","volume":"17","author":[{"given":"Yangli","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Geriatrics Zhongshan Hospital, Fudan University  Shanghai China"},{"name":"Department of Molecular Diabetology, Diabetes Research Center Japan Institute for Health Security  Tokyo 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