{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:53:49Z","timestamp":1791557629045,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"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":["82341094"],"award-info":[{"award-number":["82341094"]}],"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":["82071352"],"award-info":[{"award-number":["82071352"]}],"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":["82171675"],"award-info":[{"award-number":["82171675"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2025A1515140091"],"award-info":[{"award-number":["2025A1515140091"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515011156"],"award-info":[{"award-number":["2022A1515011156"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515010458"],"award-info":[{"award-number":["2021A1515010458"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metabolic dysfunction\u2010associated steatotic liver disease (MASLD) is characterized by abnormalities in secreted protein biosynthesis. A comprehensive understanding of secreted proteins could lead to improved diagnostics and therapies for MASLD. This study investigates the therapeutic potential of lipocalin 13 (LCN13), a lipocain family protein, in MASLD and its more severe form, metabolic dysfunction\u2010associated steatohepatitis (MASH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We screened critical lipocalins linked to MASLD using the Gene Expression Omnibus databases, analysing data from both mice and humans. The functional role of LCN13 was assessed in global knockout mice and in two murine MASLD models. We investigated LCN13's impact on glucose intolerance, insulin resistance, hepatic steatosis, and metabolic dysfunction in C57BL\/6J mice subjected to high\u2010fat and methionine\u2013choline\u2010deficient diets. The methodologies employed included Western blotting, quantitative real\u2010time polymerase chain reaction (qPCR), enzyme\u2010linked immunosorbent assay (ELISA), haematoxylin and eosin staining (H&amp;E), and Oil Red O staining. Furthermore, we employed co\u2010immunoprecipitation (co\u2010IP), LC\u2013MS\/MS, Western blotting, and qPCR to investigate the underlying mechanisms involved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LCN13 expression was significantly reduced in both mouse and human MASLD cases. Administration of recombinant LCN13 protein (rLCN13) improved conditions like hepatic steatosis, inflammation, and hepatocyte injury in diet\u2010challenged mice, whereas LCN13 knockout worsened these effects. Mechanistically, LCN13 was found to inhibit the activation of the ERK signalling pathway by interacting with the extracellular loop 2 (ECL2) of the ADRB2, thereby representing a novel target for LCN13. This interaction suppressed CD36 expression, impacting lipid transport signalling and subsequently slowing the MASLD and MASH progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings highlight the protective role of LCN13 in MASLD and MASH, offering a new therapeutic approach for these metabolic disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70858","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:03:06Z","timestamp":1788843786000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipocalin 13 Mitigates Metabolic Dysfunction\u2010Associated Steatotic Liver Disease Through Inhibiting the\n                    <scp>ADRB2<\/scp>\n                    \/\n                    <scp>ERK<\/scp>\n                    Signalling Pathway"],"prefix":"10.1111","volume":"46","author":[{"given":"Xingliang","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Endocrinology The First Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Hong","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Laboratory Standard, Department of Immunology and Microbiology, Zhongshan School of Medicine Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Department of Neurosurgery, Affiliated Nanhua Hospital, Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2440-1410","authenticated-orcid":false,"given":"Weishu","family":"Ren","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Laboratory Standard, Department of Immunology and Microbiology, Zhongshan School of Medicine Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gewen","family":"Lei","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Laboratory Standard, Department of Immunology and Microbiology, Zhongshan School of Medicine Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8200-1562","authenticated-orcid":false,"given":"Weiwei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Laboratory Standard, Department of Immunology and Microbiology, Zhongshan School of Medicine Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0156-3141","authenticated-orcid":false,"given":"Siqi","family":"Wu","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Laboratory Standard, Department of Immunology and Microbiology, Zhongshan School of Medicine Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zifan","family":"Lin","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Laboratory Standard, Department of Immunology and Microbiology, Zhongshan School of Medicine Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyao","family":"Tan","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Laboratory Standard, Department of Immunology and Microbiology, Zhongshan School of Medicine Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyuan","family":"Cao","sequence":"additional","affiliation":[{"name":"Guangzhou Jishiyuan Bio\u2010Technology Co., Ltd.  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