{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:53:53Z","timestamp":1791248033633,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"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":[[2025,8]]},"abstract":"ABSTRACT<\/jats:title>Background<\/jats:title>Intramuscular fat (IMF) is a key determinant of meat quality. Excessive IMF deposition, commonly observed in human obesity and aging, negatively affects skeletal muscle function. Circular RNAs (circRNAs) play critical regulatory roles in muscle and fat development, as well as in the progression of related diseases. However, the specific functions and underlying mechanisms of circRNAs in IMF deposition have not been extensively studied.<\/jats:p><\/jats:sec>Methods<\/jats:title>We screened adipogenic differentiation\u2010related circRNAs using circRNA\u2010seq combined with WGCNA. Functional analyses, including loss\u2010of\u2010function and gain\u2010of\u2010function experiments, were performed to determine the role of circGLIS3<\/jats:italic> in regulating adipogenesis in bovine intramuscular preadipocytes and 3T3\u2010L1 cells. A high\u2010fat diet\u2010induced mouse model was established to investigate the in\u00a0vivo effects of circGLIS3<\/jats:italic> on skeletal muscle fat infiltration in mice (C57BL\/6; n<\/jats:italic>\u2009=\u20096 males). Mechanistic studies involved transcriptomic analysis, dual\u2010luciferase reporter assays, RNA immunoprecipitation, and rescue experiments.<\/jats:p><\/jats:sec>Results<\/jats:title>We screened and characterized a novel circRNA, circGLIS3<\/jats:italic>, which is highly expressed in bovine IMF tissue and in the skeletal muscle of mice exhibiting fat infiltration. Functionally, circGLIS3<\/jats:italic> overexpression inhibited triglyceride synthesis (\u221216.19%, p<\/jats:italic>\u2009<\u20090.01) and lipid droplet accumulation (\u221242.44%, p<\/jats:italic>\u2009<\u20090.01) in intramuscular preadipocytes, concurrently downregulating the expression of key adipogenesis\u2010related genes and proteins (p<\/jats:italic>\u2009<\u20090.05). CircGLIS3<\/jats:italic> knockdown promoted triglyceride synthesis (+28.32%, p<\/jats:italic>\u2009<\u20090.05) and lipid droplet accumulation (+47.40%, p<\/jats:italic>\u2009<\u20090.01) in intramuscular preadipocytes, accompanied by a significant upregulation of adipogenesis\u2010related genes and proteins (p<\/jats:italic>\u2009<\u20090.05). Notably, circGLIS3<\/jats:italic> exhibits more than 80% sequence homology among bovine, mouse, and human species. CircGLIS3<\/jats:italic> overexpression inhibited triglyceride synthesis (\u221228.84%, p<\/jats:italic>\u2009<\u20090.01) and lipid droplet accumulation (\u221246.49%, p<\/jats:italic>\u2009<\u20090.01) in 3T3\u2010L1 cells, concurrently downregulating the expression of adipogenesis\u2010related genes and proteins (p<\/jats:italic>\u2009<\u20090.05). Overexpression of circGLIS3<\/jats:italic> reduced skeletal muscle fat infiltration induced by high\u2010fat diet in mice (\u221257.88%, p<\/jats:italic>\u2009<\u20090.05). Mechanistically, circGLIS3<\/jats:italic> acts as a sponge for miR\u201021\u20103p, increasing the expression of its target gene, LEPR<\/jats:italic> (+56.05%, p<\/jats:italic>\u2009<\u20090.01), and promoting the phosphorylation level of its downstream signalling protein, AMPK\u03b1 (+68.68%, p<\/jats:italic>\u2009<\u20090.01).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>CircGLIS3<\/jats:italic> inhibits bovine intramuscular adipogenesis by regulating the miR\u201021\u20103p\/LEPR\/AMPK axis, reducing fat infiltration in mouse skeletal muscle. These findings suggest that circGLIS3<\/jats:italic> is a promising target for improving meat quality in livestock, and as a potential therapeutic marker for alleviating skeletal muscle fat infiltration associated with obesity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.70009","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:21:01Z","timestamp":1753867261000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["CircGLIS3<\/i> Inhibits Intramuscular Adipogenesis and Alleviates Skeletal Muscle Fat Infiltration"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1557-3760","authenticated-orcid":false,"given":"Shengchen","family":"Yu","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology Northwest A&F University Yangling China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfang","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Northwest A&F University Yangling China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibing","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Northwest A&F University Yangling China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juntao","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Northwest A&F University Yangling China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abebe\u00a0Belete","family":"Kuraz","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Northwest A&F University Yangling 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