{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:40:54Z","timestamp":1791942054956,"version":"4.3.4"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sarcopenia is highly prevalent in individuals with diabetes and is associated with impaired physical function and increased mortality. Diabetes-associated skeletal muscle atrophy is driven by chronic inflammation, dysregulated anabolic\u2013catabolic signaling, and activation of ubiquitin\u2013proteasome\u2013mediated protein degradation. Emerging evidence suggests that histone deacetylases (HDACs) act as epigenetic regulators of metabolic and inflammatory pathways; however, their role in diabetic sarcopenia remains incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male\n                      <jats:italic>db\/db<\/jats:italic>\n                      mice were used as a model of diabetes-associated muscle atrophy and treated with MS-275 (entinostat), a selective class I HDAC inhibitor, for 4 weeks. Skeletal muscle mass and fiber cross-sectional area were assessed by magnetic resonance imaging and histological analysis. Inflammatory responses, myostatin signaling, and Akt\/ARK5\u2013FoxO\u2013mediated catabolic pathways were evaluated using immunohistochemistry, quantitative PCR, ELISA, and western blotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MS-275 treatment significantly restored skeletal muscle mass and myofiber size in\n                      <jats:italic>db\/db<\/jats:italic>\n                      mice. These effects were accompanied by marked reductions in macrophage infiltration, pro-inflammatory cytokine expression, and NF-\u03baB activation. MS-275 also suppressed circulating myostatin levels and attenuated downstream Smad2\/3 signaling. Furthermore, MS-275 restored Akt and ARK5 phosphorylation and promoted FoxO1\/3 phosphorylation, resulting in decreased expression of the muscle-specific E3 ubiquitin ligases MuRF1 and atrogin-1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings demonstrate that epigenetic inhibition of class I HDACs by MS-275 attenuates diabetes-associated skeletal muscle atrophy by coordinately suppressing inflammatory signaling and myostatin-driven catabolic pathways while restoring Akt\/ARK5\u2013FoxO signaling. These results suggest that class I HDACs are key epigenetic regulators of diabetic muscle wasting and that targeting their activity provides important mechanistic insights for preserving skeletal muscle mass in diabetic sarcopenia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1788603","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:22:43Z","timestamp":1773033763000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Epigenetic inhibition of class I histone deacetylases by MS-275 attenuates diabetic skeletal muscle atrophy via Akt\/ARK5\u2013FoxO and myostatin\u2013Smad signaling"],"prefix":"10.3389","volume":"17","author":[{"given":"Youngho","family":"Son","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Ajou University School of Medicine","place":["Suwon, Republic of Korea"]},{"name":"Department of Biomedical 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