{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:36:31Z","timestamp":1789662991876,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Skeletal muscle atrophy occurs in various situations, such as denervation, fasting and ageing. Disruption of the balance between protein synthesis and degradation plays an important role in muscle atrophy, and impaired Akt phosphorylation is considered to be crucial in this process. The attachment of an O\u2010linked N\u2010acetylglucosamine motif (O\u2010GlcNAcylation), which is a post\u2010translational modification mediated by the hexosamine biosynthetic pathway, an alternative pathway of glycolysis, is involved in the regulation of protein function. Akt O\u2010GlcNAcylation interacts with Akt phosphorylation, thereby regulating its function. The purpose of this study was to clarify the role of O\u2010GlcNAcylation in skeletal muscle atrophy and to identify a therapeutic target for its prevention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Denervation was induced by cutting the sciatic nerve on the right leg of male C57BL\/6J mice. A sham operation was performed on the left leg. Three days after the operation, the mice were divided into two groups: One group was treated with the O\u2010GlcNAcase inhibitor thiamet G (1\u2009mg\/kg body weight\/day), and the other group was treated with vehicle. Seven days after the operation, the gastrocnemius muscle was collected and analysed. The effect of adeno\u2010associated virus serotype 1\u2013mediated suppression of O\u2010GlcNAcase on skeletal muscle atrophy was also investigated. Finally, in C2C12 myotubes with adenovirus\u2010mediated overexpression of wild\u2010type Akt and O\u2010GlcNAcylation\u2010resistant mutant Akt (T479A), the interaction between the phosphorylation and O\u2010GlcNAcylation of Akt was investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The weight of denervated gastrocnemius muscle was decreased by 35.6% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) compared with sham. Akt phosphorylation was decreased by 27.8% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), and the expression of the muscle\u2010specific ubiquitin ligases muscle atrophy F\u2010box (atrogin\u20101) and muscle RING Finger\u20101 (MuRF1) was increased in denervated muscle compared with sham. Akt O\u2010GlcNAcylation was decreased in denervated muscle compared with sham by 45.3% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), together with an 8.9\u2010fold increase in O\u2010GlcNAcase expression. Thiamet G reduced gastrocnemius muscle weight loss by 22.7% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) compared with vehicle, and this was achieved through an increase in Akt phosphorylation by 63.5% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) and decreases in atrogin\u20101 and MuRF1 expression. The inhibition of O\u2010GlcNAcase by gene silencing also improved skeletal muscle atrophy. The overexpression of mutant Akt (T479A) showed less O\u2010GlcNAcase inhibition\u2010induced Akt phosphorylation than the overexpression of wild\u2010type Akt.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>O\u2010GlcNAcase inhibition improved denervation\u2010induced skeletal muscle atrophy in mice by increasing Akt O\u2010GlcNAcylation. O\u2010GlcNAcase may hence be a therapeutic target for preventing skeletal muscle atrophy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70066","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T09:15:06Z","timestamp":1757668506000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["O\u2010GlcNAcase Inhibitor Improves Denervation\u2010Induced Muscle Atrophy in Mice"],"prefix":"10.1002","volume":"16","author":[{"given":"Tomoyasu","family":"Suenaga","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Faculty of Medical Sciences Kyushu University  Fukuoka Japan"},{"name":"Division of Cardiovascular Medicine, Research Institute of Angiocardiology, Faculty of Medical Sciences Kyushu University  Fukuoka 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