{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:45:02Z","timestamp":1792043102338,"version":"4.4.0"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LR20H310001"],"award-info":[{"award-number":["LR20H310001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Metabolic dysfunction\u2010associated steatotic liver disease (MASLD) is associated with disturbances in arachidonic acid (AA) metabolism; however, the role and regulation of cyclooxygenase\u20102 (COX\u20102), a key enzyme in AA metabolism, during disease progression remain incompletely understood. Here, we identify fibroblast growth factor 21 (FGF21) as a previously unrecognized suppressor of hepatic COX\u20102 in MASLD. Although both FGF21 and COX\u20102 were elevated in steatotic livers, FGF21 deficiency further augmented hepatic COX\u20102 expression in mice fed with a high\u2010fat diet, leading to dysregulated AA metabolism, excessive prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ) production, aggravated inflammation, oxidative stress, and fibrosis. Conversely, adeno\u2010associated virus (AAV)\u2010mediated restoration of FGF21 normalized COX\u2010derived AA metabolites, suppressed COX\u20102 activation, and ameliorated hepatic injury. Pharmacological inhibition of COX\u20102 partially recapitulated the protective effects of FGF21 but failed to reverse fibrosis, suggesting that COX\u20102 contributes to disease progression but is not sufficient to account for fibrosis. Mechanistically, FGF21 suppressed COX\u20102 through a PPAR\u03b1\u2010dependent pathway, whereas ERK1\/2 phosphorylation acted upstream of the FGF21\/PPAR\u03b1 axis. In patients with MASLD, circulating PGE\n                    <jats:sub>2<\/jats:sub>\n                    was positively associated with liver injury after adjustment for body mass index and hepatic steatosis. Collectively, the FGF21\u2010PPAR\u03b1\u2010COX\u20102 axis represents a critical regulator of AA metabolic remodeling and a potential therapeutic target for MASLD.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70999","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:11:37Z","timestamp":1789459897000},"source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of COX\u20102\u2010Mediated Arachidonic Acid Metabolism by FGF21\u2010PPAR\u03b1 Axis Alleviates Liver Steatosis"],"prefix":"10.1002","volume":"7","author":[{"given":"Guangsen","family":"Xu","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University University Town  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University University Town  Wenzhou China"},{"name":"Taizhou 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojian","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases The Sixth Affiliated Hospital of Wenzhou Medical University Lishui People's Hospital  Lishui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baile","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong  Hong Kong China"},{"name":"Department of Medicine The University of Hong Kong  Hong Kong China"},{"name":"Guangdong\u2010Hong Kong Joint Laboratory for Metabolic Medicine The University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuebo","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University University Town  Wenzhou 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