{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:30:15Z","timestamp":1772991015352,"version":"3.50.1"},"reference-count":56,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"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","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Metabolic dysfunction\u2010associated steatotic liver disease (MASLD) presents a high incidence globally and is a major cause of cirrhosis and hepatocellular carcinoma, lacking of efficient interventions. Patients with MASLD exhibit exceeded serum levels of palmitic acid (PA). However, the association between PA and MASLD remains obscure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Gene expression omnibus dataset analysis, western blotting, mRNA\u2010sequencing, RT\u2010qPCR, a click chemistry\u2010immunoprecipitation\u2010immunofluorescence system, ELISA, lipid extraction and UHPLC\u2013MS\/MS analysis, CyTOF mass cytometry, gene knockdown via lentivirus\u2010mediated shRNA, and high\u2010fat methionine and choline\u2010deficient diet\u2010fed WT and db\/db mice models were used to reveal the expression and functions of Porcupine in MASLD development both in\u00a0vitro and in\u00a0vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings show that PA, as a crucial substrate for protein palmitoylation, induced the expression of palmitoyltransferase Porcupine in a time\u2010dependent manner. This induction was closely associated with dysregulated lipid metabolism and stimulated inflammatory response observed in\u00a0vitro. Porcupine protein levels were significantly increased in liver tissues from both MASLD mice models, which was predominantly localised in lipid droplet\u2010rich hepatocytes. Pharmacological inhibition of Porcupine by Wnt974 markedly ameliorated the aberrant lipid accumulation and inflammatory response in mouse livers. Furthermore, increased Porcupine positively correlated with CD36 at protein levels, and its inhibition or knockdown decreased CD36 protein levels via mechanisms irrelevant to transcriptional regulation, but primarily dependent on protein palmitoylation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The current study reveals that PA\u2010induced Porcupine disrupts lipid metabolism and promotes inflammatory response during MASLD development, which can be ameliorated by the Porcupine inhibitor Wnt974. Therefore, Porcupine may be a potential pharmacological target for the treatment of MASLD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.16130","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T05:14:32Z","timestamp":1728969272000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Elevated Porcupine Disrupts Lipid Metabolism and Promotes Inflammatory Response in\n                    <scp>MASLD<\/scp>"],"prefix":"10.1111","volume":"45","author":[{"given":"Yalin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacology and School of Basic Medicine Clinical Pharmacy China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengyu","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and School of Basic Medicine Clinical Pharmacy China 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