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This study examines how fatty acid metabolism in hepatic macrophages shapes AILI progression. APAP was used to induce acute injury in mice, and lipid and macrophage functional changes were assessed. Mechanistically, HMGB1 from necrotic hepatocytes elevates FASN via PI3K/AKT/SREBP1, enhancing inflammatory factors and macrophage migration.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/targeting-fatty-acid-metabolism-in-hepatic-macrophages-mitigates-acetaminophen-induced-liver-injury-and-promotes-regeneration-in-mice/442861/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/targeting-fatty-acid-metabolism-in-hepatic-macrophages-mitigates-acetaminophen-induced-liver-injury-and-promotes-regeneration-in-mice/442861.png","ImageObject",300,407,{"name":92,"@type":93},"LangkahRina","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does APAP overdose lead to liver injury in this work?","Question",{"text":112,"@type":113},"The study describes APAP producing toxic reactive metabolites that exhaust glutathione, damage mitochondria and DNA, and cause hepatocyte necrosis, which intensifies sterile inflammation through activation and recruitment of immune cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What role does fatty acid metabolism in hepatic macrophages play in AILI?",{"text":117,"@type":113},"The findings show elevated lipid levels and increased inflammatory signaling in hepatic macrophages after AILI. These changes are linked to enhanced de novo lipogenesis that supports macrophage inflammatory factor expression and migration.",{"name":119,"@type":110,"acceptedAnswer":120},"Which molecular pathway connects HMGB1 to macrophage lipogenesis?",{"text":121,"@type":113},"HMGB1 released from necrotic hepatocytes increases FASN expression by activating the PI3K/AKT/SREBP1 signaling pathway in macrophages.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},442861,1790800841,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962090893776,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","DOI: 10.1097/HC9.0000000000000865  \nO R IG INAL ART ICL E  \nTargeting fatty acid metabolism in hepatic macrophages mitigates acetaminophen-induced liver injury and promotes regeneration in mice  \nXiaoyong Jiang 1 | Beng Wu1 | Liuyu Xie2 | Hao Li2 | Chen Chen 1 |  \nPanpan Huang2 | Xiaoyu Chen3 | Qian Zhu 1,4,5 | Hua Wang5,6 | Chaojie Hu2  \n1School of Pharmaceutic Science, Anhui Medical University, Hefei, China 2Division of Life Science and Medicine, Department of Clinical Laboratory, First Affiliated Hospital of USTC, University of  \nScience and Technology of China, Hefei, Anhui, China  \n3Anhui International Travel Health Care Center, Hefei, China  \n4Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China  \n5Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, China  \n6Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, China  \nCorrespondence  \nChaojie Hu, Division of Life Science and Medicine, Department of Clinical Laboratory, The First Affiliated Hospital of USTC, University of Science and Technology of China, Lujiang Road, Hefei 230001, China.  \nEmail: [hucj2018@ustc.edu.cn](hucj2018@ustc.edu.cn)  \nHua Wang, Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, Jixi Road, 230022, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Meishan Road, Hefei, 230032, China. [Email:](Email: wanghua@ahmu.edu.cn)[ wanghua@ahmu.edu.cn](Email: wanghua@ahmu.edu.cn)  \nQian Zhu, School of Pharmacy, Anhui Medical University, Meishan Road, Hefei, 230032, China.  \nEmail: [zhuqian@ahmu.edu.cn](zhuqian@ahmu.edu.cn)  \n\n|  | Abstract |  |\n| --- | --- | --- |\n| | Background: An overdose of acetaminophen (APAP) can cause severe liver injury and may even lead to death. However, the mechanisms that underlie APAP-induced liver injury (AILI) are not fully understood. The extensive liver necrosis resulting from APAP overdose aggravates the sterile inflammatory response by activating resident macrophages and recruiting various immune cells. Numerous studies have highlighted the crucial role of lipid metabolism in macrophage function. This study investigated fatty acid metabolism in hepatic macrophages and its impact on the progression of AILI.\u003Cbr>Methods: We administered APAP intraperitoneally to C57/B6L mice to induce acute liver injury and studied lipid changes in hepatic macrophages. We treated hepacytes with APAP and collected the conditioned medium to stimulate macrophages. Moreover, we generated a myeloid-specific knockout of Fasn mice to validate the role of de novo lipogenesis in macrophages during AILI.\u003Cbr>Results: We stained liver tissue sections with Bodipy493/503 lipid dye and observed elevated lipid levels in hepatic macrophages after AILI. Mechanistically, HMGB1 released from necrotic hepatocytes increases FASN expression by activating the PI3K/AKT/sterol regulatory element-binding protein-1 (SREBP1) signaling pathway in macrophages. The enhanced de novo lipogenesis increased inflammatory factor expression in macrophages and facilitated their migratory ability. Conversely, myeloid-specific knockout of Fasn reduced the inflammatory response of macrophages and inhibited |  |\n|  |  |  |\n\nAbbreviations: APAP, acetaminophen; AILI, acetaminophen-induced liver injury; BMDM, bone marrow–derived macrophage; CM, conditioned medium; DNL, de novo lipogenesis; FASN, fatty acid synthase; HMGB1, high-mobility group protein B1; PI3K, phosphatidylinositol 3-kinase; MoM, monocyte-derived macrophage; SREBP1, sterol regulatory element-binding protein-1 .  \nXiaoyong Jiang, Beng Wu, and Liuyu Xie contributed equally to this work.  \nSupplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website, www.hepcommjournal.com.  \n-- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- -----","cbCaip6kvAyN88tJ","https://ap.wps.com/l/cbCaip6kvAyN88tJ","pdf",1685429,15,"English","# Abstract\n# Introduction","[{\"question\":\"How does APAP overdose lead to liver injury in this work?\",\"answer\":\"The study describes APAP producing toxic reactive metabolites that exhaust glutathione, damage mitochondria and DNA, and cause hepatocyte necrosis, which intensifies sterile inflammation through activation and recruitment of immune cells.\"},{\"question\":\"What role does fatty acid metabolism in hepatic macrophages play in AILI?\",\"answer\":\"The findings show elevated lipid levels and increased inflammatory signaling in hepatic macrophages after AILI. These changes are linked to enhanced de novo lipogenesis that supports macrophage inflammatory factor expression and migration.\"},{\"question\":\"Which molecular pathway connects HMGB1 to macrophage lipogenesis?\",\"answer\":\"HMGB1 released from necrotic hepatocytes increases FASN expression by activating the PI3K/AKT/SREBP1 signaling pathway in macrophages.\"}]","Targeting fatty acid metabolism in hepatic macrophages mitigates acetaminophen-induced liver injury and promotes regeneration in mice | PDF",1790701891,38]