{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T08:17:18Z","timestamp":1787991438747,"version":"build-2784847793"},"reference-count":45,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270438"],"award-info":[{"award-number":["32270438"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32170498"],"award-info":[{"award-number":["32170498"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32400574"],"award-info":[{"award-number":["32400574"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32500408"],"award-info":[{"award-number":["32500408"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2023ZD0506800"],"award-info":[{"award-number":["2023ZD0506800"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M752193"],"award-info":[{"award-number":["2024M752193"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M752198"],"award-info":[{"award-number":["2024M752198"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Metabolic dysfunction\u2010associated steatotic liver disease (MASLD) poses an increasing threat to global public health. Currently approved drugs for MASLD, such as resmetirom and semaglutide, have demonstrated clinical efficacy. However, their use is associated with notable adverse effects, including serious gastrointestinal reactions, metabolic and nutritional disturbances, and renal or urinary system disorders. The present study established that the expression levels of a liver\u2010secreted protein, the \u201cout at first homolog\u201d (\n                    <jats:italic>Oaf<\/jats:italic>\n                    ) gene product, are closely associated with metabolic disorders in humans and mice. In a high\u2010fat diet (HD) feeding mouse model,\n                    <jats:italic>Oaf<\/jats:italic>\n                    \u2010deficiency exacerbated hepatic lipid accumulation, whereas intraperitoneal injection of OAF protein ameliorated the development of MASLD. Mechanistically, OAF binds to SCPX and acts as a chaperone, preventing SCPX from degradation by SIAH1\u2010mediated ubiquitination. This stabilizes SCPX and increases its abundance, thereby enhancing cholesterol transport, lipid esterification, and lipid excretion, while inhibiting lipid biosynthesis. In mice, deficiency of either\n                    <jats:italic>Oaf<\/jats:italic>\n                    or\n                    <jats:italic>Scpx<\/jats:italic>\n                    reduced these effects. Collectively, our findings identify OAF as a novel therapeutic target for the treatment of MASLD and provide a rationale for further drug development targeting human fatty liver diseases.\n                  <\/jats:p>","DOI":"10.1002\/advs.77451","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T08:07:06Z","timestamp":1787990826000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["OAF Blocks SIAH1\u2010Mediated Degradation of SCPX, a Therapeutic Strategy for MASLD"],"prefix":"10.1002","author":[{"given":"Zongxi","family":"Li","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory For Biodiversity and Biotechnology College of Life Sciences Nanjing Normal University  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyue","family":"Song","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory For Biodiversity and Biotechnology College of Life Sciences Nanjing Normal University  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaili","family":"Ma","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory For Biodiversity and Biotechnology College of Life Sciences Nanjing Normal University  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunan","family":"Tang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory For Biodiversity and Biotechnology College of Life Sciences Nanjing Normal University  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqian","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory For Biodiversity and Biotechnology College of Life Sciences Nanjing Normal University  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenya","family":"Ji","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory For Biodiversity and Biotechnology College of Life Sciences Nanjing Normal University  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Lu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory For Biodiversity and Biotechnology College of Life Sciences Nanjing Normal University  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of High Altitude Medicine Center For High Altitude Medicine College of Life Sciences National Clinical Research Center for Geriatrics West China Hospital Sichuan University  Chengdu Sichuan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0716-8987","authenticated-orcid":false,"given":"Huaping","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of High Altitude Medicine Center For High Altitude Medicine College of Life Sciences National Clinical Research Center for Geriatrics West China Hospital Sichuan University  Chengdu Sichuan People's Republic of China"},{"name":"Institute of High Altitude Medicine High Altitude Medicine Key Laboratory of Sichuan Province West China Hospital Sichuan University  Chengdu Sichuan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2648-1119","authenticated-orcid":false,"given":"Xiaowei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery Karolinska Institute  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7316-678X","authenticated-orcid":false,"given":"Shanshan","family":"Lai","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory For Biodiversity and Biotechnology College of Life Sciences Nanjing Normal University  Nanjing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5296-8879","authenticated-orcid":false,"given":"Cheng","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of High Altitude Medicine Center For High Altitude Medicine College of Life Sciences National Clinical Research Center for Geriatrics West China Hospital Sichuan University  Chengdu Sichuan People's Republic of China"},{"name":"Institute of High Altitude Medicine High Altitude Medicine Key Laboratory of Sichuan Province West China Hospital Sichuan University  Chengdu Sichuan People's Republic of China"},{"name":"Center For High Altitude Medicine  Xining Qinghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.03.039"},{"key":"e_1_2_9_3_1","article-title":"A Comprehensive Review on Non\u2010Alcoholic Fatty Liver Disease","volume":"15","author":"Sahu P.","year":"2023","journal-title":"Cureus Journal of Medical Science"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3390\/nu14010103","article-title":"Metabolic\u2010Associated Fatty Liver Disease (MAFLD), Diabetes, and Cardiovascular Disease: Associations with Fructose Metabolism and Gut Microbiota","volume":"14","author":"Dro\u017cd\u017c K.","year":"2021","journal-title":"Nutrients"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.109"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2309000"},{"key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1056\/NEJMoa2413258","article-title":"Phase 3 Trial of Semaglutide in Metabolic Dysfunction\u2010Associated Steatohepatitis","volume":"392","author":"Sanyal A. J.","year":"2025","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13679\u2010026\u201000707\u20106"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.4183\/aeb.2024.494"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1416985"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2024.e34837","article-title":"Pharmacovigilance Analysis Of Orlistat Adverse Events Based on the FDA Adverse Event Reporting System (FAERS) database","volume":"10","author":"Zhu J. F.","year":"2024","journal-title":"Heliyon"},{"key":"e_1_2_9_12_1","first-page":"578","article-title":"Metabolic Dysfunction\u2010Associated Steatotic Liver Disease: Diagnosis and Management","volume":"113","author":"Ohri S.","year":"2026","journal-title":"American Family Physician"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/139.3.1331"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2017.12.012"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864\u2010023\u201009400\u20107"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15296"},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s13020-023-00793-x","article-title":"Yin\/Yang Associated Differential Responses to Psoralea corylifolia Linn. In Rat Models: An Integrated Metabolomics And Transcriptomics Study","volume":"18","author":"Zhang M. L.","year":"2023","journal-title":"Chinese Medicine"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2022.08.002"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201011576\u20100"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioadv\/vbac087"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022\u20102275(20)34472\u20102"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2022.155180"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163\u20107827(01)00015\u20107"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00460.2014"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00446.2009"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00195.2011"},{"key":"e_1_2_9_27_1","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1086\/503921","article-title":"Mutations in the Gene Encoding Peroxisomal Sterol Carrier Protein X (SCPx) Cause Leukencephalopathy With Dystonia And Motor Neuropathy","volume":"78","author":"Ferdinandusse S.","year":"2006","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40246\u2010022\u201000408\u2010w"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110897"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010025\u201002215\u2010w"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.314"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4645"},{"key":"e_1_2_9_33_1","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1039\/D2CB00187J","article-title":"Abilities of the BRICHOS Domain To Prevent Neurotoxicity And Fibril Formation Are Dependent On A Highly Conserved Asp Residue","volume":"3","author":"Chen G. F.","year":"2022","journal-title":"Rsc Chemical Biology"},{"key":"e_1_2_9_34_1","doi-asserted-by":"crossref","first-page":"4234","DOI":"10.1016\/j.apsb.2023.07.027","article-title":"MANF brakes TLR4 Signaling By Competitively Binding S100A8 with S100A9 to Regulate Macrophage Phenotypes In Hepatic Fibrosis","volume":"13","author":"Hou C.","year":"2023","journal-title":"Acta Pharmaceutica Sinica B"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255\u2010019\u20100065\u20104"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010017\u201002677\u20109"},{"key":"e_1_2_9_37_1","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.201708791","article-title":"FGF21 Gene Therapy As Treatment For Obesity And Insulin Resistance","volume":"10","author":"Jimenez V.","year":"2018","journal-title":"Embo Molecular Medicine"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.01.006"},{"key":"e_1_2_9_39_1","doi-asserted-by":"crossref","first-page":"260","DOI":"10.2337\/db23-0357","article-title":"Roles of Activin A and Gpnmb in Metabolic Dysfunction\u2010Associated Steatotic Liver Disease (MASLD)","volume":"73","author":"Liu H.","year":"2024","journal-title":"Diabetes"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201028889\u20102"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202514545"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102023\u2010330595"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201068188\u20100"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2009.09.010"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msx252"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.215"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77451","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.77451","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77451","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T08:07:09Z","timestamp":1787990829000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.77451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,29]]},"references-count":45,"alternative-id":["10.1002\/advs.77451"],"URL":"https:\/\/doi.org\/10.1002\/advs.77451","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,29]]},"assertion":[{"value":"2026-02-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e77451"}}