{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T19:28:37Z","timestamp":1773257317986,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"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":["82204953"],"award-info":[{"award-number":["82204953"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022M710552"],"award-info":[{"award-number":["2022M710552"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aocs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Lipids"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The precise involvement of ACSL1 in metabolic\u2010associated fatty liver disease (MAFLD) pathogenesis remains unclear. To this end, we analyzed the effects of long\u2010chain acyl\u2010CoA synthase (ACSL1) on MAFLD. Analysis of GEO datasets showed that ACSL1 was downregulated in MAFLD. To elucidate its mechanistic role, we generated BRL hepatocyte cell lines with stable ACSL1 knockdown or overexpression. These engineered cells were cultured with a lipid mixture containing 300\u2009\u03bcM oleic acid, 150\u2009\u03bcM palmitic acid, and 100\u2009\u03bcM linoleic acid (OPL) to mimic MAFLD pathophysiology in\u00a0vitro. Lipidomic profiling identified 195 upregulated and 357 downregulated lipid metabolites in OPL\u2010treated ACSL1\u2010knockdown cells (OPL\u2010shACSL1). Notably, the OPL\u2010shACSL1 group exhibited marked elevations in free fatty acids, including linoleic acid, arachidonic acid (AA), FA20:3, FA22:5, and FA22:2, accompanied by enhanced AA metabolism. Western blotting demonstrated that ACSL1 knockdown significantly upregulated key enzymes in AA metabolic pathways, including ELOVL5, COX1, and LOX5. Consistent with these in\u00a0vitro findings, mice with high\u2010fat diet\u2010induced MAFLD showed reduced hepatic ACSL1 expression with concurrent elevation of COX1 protein levels. Co\u2010immunoprecipitation assays showed that ACSL1 did not interact with LOX5 or COX1. Our findings demonstrate that ACSL1 knockdown enhances AA metabolism, evidenced by elevated levels of AA\u2010related metabolites and upregulated expression of key enzymes (ELOVL5, COX1, LOX5), and suggest that ACSL1 may represent a potential therapeutic target for MAFLD.<\/jats:p>","DOI":"10.1002\/lipd.70016","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T07:45:05Z","timestamp":1762415105000},"page":"175-185","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>ACSL1<\/scp>\n                    Contributes to Metabolic\u2010Associated Fatty Liver Disease by Mediating Arachidonic Acid Metabolism"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3364-9976","authenticated-orcid":false,"given":"Meiao","family":"Tan","sequence":"first","affiliation":[{"name":"First Clinical Medical College Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Chongqing Traditional Chinese Medicine Hospital  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zunming","family":"Zhou","sequence":"additional","affiliation":[{"name":"First Clinical Medical College Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chong","family":"Peng","sequence":"additional","affiliation":[{"name":"First Clinical Medical College Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuehong","family":"Ke","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Long","sequence":"additional","affiliation":[{"name":"Chongqing Traditional Chinese Medicine Hospital  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keer","family":"Huang","sequence":"additional","affiliation":[{"name":"First Clinical Medical College Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"397","article-title":"TNF\u2010\u03b1 Induces a Pro\u2010Inflammatory Phenotypic Shift in Monocytes Through ACSL1: Relevance to Metabolic Inflammation","volume":"52","author":"Al\u2010Rashed F.","year":"2024","journal-title":"Cellular Physiology and 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