{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:34:56Z","timestamp":1793043296055,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272421"],"award-info":[{"award-number":["82272421"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatic lipid deposition is a key factor in progressing metabolic dysfunction\u2010associated steatotic liver disease (MASLD). This study investigates the impact of the LIM domain and actin\u2010binding protein 1 (LIMA1) on hepatic steatotic in MASLD and explore the underlying mechanisms. Increased levels of LIMA1 is observed in both serum and serum sEV of metabolic dysfunction\u2010associated steatohepatitis (MASH) patients compared to healthy controls, with AUROC values of 0.76 and 0.86, respectively. Furthermore, increased LIMA1 O\u2010GlcNAcylation is observed in mouse models of MASLD, and steatotic hepatocytes. Mechanistic studies revealed that steatosis upregulated Host cell factor 1 (HCF1) and O\u2010GlcNAc transferase (OGT) expression, leading to catalyzed O\u2010GlcNAcylation at the T662 site of LIMA1 and subsequent inhibition of its ubiquitin\u2010dependent degradation. O\u2010GlcNAcylation of LIMA1 enhances hepatocyte lipid deposition by activating \u03b2\u2010catenin\/FASn\u2010associated signaling. Additionally, compared with their AAV8\u2010TBG\u2010LIMA1\u2010WT counterparts, AAV8\u2010TBG\u2010LIMA1<jats:sup>\u0394T662<\/jats:sup> injection exhibited decreases in systemic insulin resistance, steatosis severity, inflammation and fibrosis in HFD\u2010fed and CDAHFD\u2010fed LIMA1 HKO (hepatocyte\u2010specific knockout) mice. Moreover, LTH\u2010sEV\u2010mediated delivery of LIMA1 promoted MASLD progression by promoting hepatic stellate cell (HSC) activation. The findings suggest that serum sEV LIMA1 may be a potential noninvasive biomarker and therapeutic target for individuals with MASH.<\/jats:p>","DOI":"10.1002\/advs.202415941","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T05:17:48Z","timestamp":1739251068000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["LIMA1 O\u2010GlcNAcylation Promotes Hepatic Lipid Deposition through Inducing \u03b2\u2010catenin\u2010Regulated FASn Expression in Metabolic Dysfunction\u2010Associated Steatotic Liver Disease"],"prefix":"10.1002","volume":"12","author":[{"given":"Fuji","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Wujin Hospital Affiliated with Jiangsu University Jiangsu University  Changzhou 213017 China"},{"name":"Department of Laboratory Medicine School of Medicine Jiangsu University  Zhenjiang 212013 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Wujin Hospital Affiliated with Jiangsu University Jiangsu University  Changzhou 213017 China"},{"name":"Department of Laboratory Medicine School of Medicine Jiangsu University  Zhenjiang 212013 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine The Third People's Hospital of Changzhou  Changzhou 213017 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kefeng","family":"Gu","sequence":"additional","affiliation":[{"name":"Changzhou Key Laboratory of Exosome Foundation and Transformation Application Wujin Hospital Affiliated with Jiangsu University Jiangsu University  Changzhou 213017 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Fan","sequence":"additional","affiliation":[{"name":"Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University Jiangsu University  Changzhou 213017 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingfen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of laboratory medicine The Second People's Hospital of Changzhou  Changzhou 213614 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhu","sequence":"additional","affiliation":[{"name":"Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University Jiangsu University  Changzhou 213017 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1990-1170","authenticated-orcid":false,"given":"Yongmin","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Wujin Hospital Affiliated with Jiangsu University Jiangsu University  Changzhou 213017 China"},{"name":"Changzhou Key Laboratory of Exosome Foundation and Transformation Application Wujin Hospital Affiliated with Jiangsu University Jiangsu University  Changzhou 213017 China"},{"name":"Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University Jiangsu University  Changzhou 213017 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,8]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvad095"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.04.019"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000670"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.03.012"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02958-z"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.71"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15490"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1556"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2021.102430"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05815"},{"key":"e_1_2_9_11_1","first-page":"13","author":"Pang Y.","year":"2021","journal-title":"Nutrients"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01316-8"},{"key":"e_1_2_9_13_1","volume":"11","author":"Zhou Y.","year":"2022","journal-title":"Cells"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15812"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1115943"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28139-5"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao6575"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2024.155914"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42427-8"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.06.008"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.07.006"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1289004"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29226"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03857-z"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31743"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32620"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2023.101238"},{"key":"e_1_2_9_28_1","first-page":"11","author":"Zeng J.","year":"2021","journal-title":"Biomolecules"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2023.101776"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.395"},{"key":"e_1_2_9_31_1","first-page":"11","author":"Lee D. E.","year":"2019","journal-title":"Nutrients"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.080572"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14043"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2016.04.035"},{"key":"e_1_2_9_35_1","first-page":"505","volume":"3","author":"Dorn C.","year":"2010","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101238"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hep.2003.09.028"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2537"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115379"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-018-1472-0"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202301166"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.798735"},{"key":"e_1_2_9_43_1","first-page":"1176","volume":"10","author":"Xue T.","year":"2022","journal-title":"J. Clin. Transl. Hepatol."},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.12.037"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.09.014"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22541"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2006.11.004"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-023-00811-0"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.10.010"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202415941","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T23:57:31Z","timestamp":1759795051000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202415941"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,8]]},"references-count":49,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/advs.202415941"],"URL":"https:\/\/doi.org\/10.1002\/advs.202415941","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,8]]},"assertion":[{"value":"2024-11-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2415941"}}