{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:52:34Z","timestamp":1790689954955,"version":"4.1.0"},"reference-count":31,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82374102"],"award-info":[{"award-number":["82374102"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Immunopharmacology"],"published-print":{"date-parts":[[2025,2]]},"DOI":"10.1016\/j.intimp.2025.114020","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T17:56:36Z","timestamp":1736445396000},"page":"114020","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"special_numbering":"C","title":["SFAs facilitates ceramide\u2019s de novo synthesis via TLR4 and intensifies hepatocyte lipotoxicity"],"prefix":"10.1016","volume":"147","author":[{"given":"Yuchao","family":"Zou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6524-2502","authenticated-orcid":false,"given":"Liuhua","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiannan","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinuo","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokai","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2465-3079","authenticated-orcid":false,"given":"Xiaobing","family":"Dou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"10215","key":"10.1016\/j.intimp.2025.114020_b0005","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1016\/S0140-6736(19)33041-7","article-title":"Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial","volume":"394","author":"Younossi","year":"2019","journal-title":"Lancet"},{"issue":"5","key":"10.1016\/j.intimp.2025.114020_b0010","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1097\/HEP.0000000000000670","article-title":"Metabolic dysfunction-associated steatotic liver disease: Update and impact of new nomenclature on the American Association for the study of liver diseases practice guidance on nonalcoholic fatty liver disease","volume":"79","author":"Kanwal","year":"2024","journal-title":"Hepatology"},{"issue":"1","key":"10.1016\/j.intimp.2025.114020_b0015","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/imr.12891","article-title":"Lipids, inflammasomes, metabolism, and disease","volume":"297","author":"Anand","year":"2020","journal-title":"Immunol. Rev."},{"issue":"2","key":"10.1016\/j.intimp.2025.114020_b0020","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/s41575-020-00406-0","article-title":"Nonalcoholic fatty liver disease: another leap forward","volume":"18","author":"Abdelmalek","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"issue":"2","key":"10.1016\/j.intimp.2025.114020_b0025","doi-asserted-by":"crossref","first-page":"E131","DOI":"10.1152\/ajpendo.00181.2019","article-title":"Amitriptyline inhibits nonalcoholic steatohepatitis and atherosclerosis induced by high-fat diet and LPS through modulation of sphingolipid metabolism","volume":"318","author":"Lu","year":"2020","journal-title":"Am. J. Phys. Endocrinol. Metab."},{"issue":"12","key":"10.1016\/j.intimp.2025.114020_b0030","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1001\/jama.2020.2298","article-title":"Nonalcoholic Steatohepatitis: A Review","volume":"323","author":"Sheka","year":"2020","journal-title":"J. Am. Med. Assoc."},{"issue":"9","key":"10.1016\/j.intimp.2025.114020_b0035","doi-asserted-by":"crossref","first-page":"5146","DOI":"10.3390\/ijms23095146","article-title":"Lipotoxicity as the leading cause of non-alcoholic steatohepatitis","volume":"23","author":"Brankovic","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.intimp.2025.114020_b0040","first-page":"47","article-title":"Role of metabolic lipases and lipotoxicity in the development of non-alcoholic steatosis and non-alcoholic steatohepatitis","volume":"28","author":"Berlanga","year":"2016","journal-title":"Clin Investig Arterioscler."},{"issue":"3","key":"10.1016\/j.intimp.2025.114020_b0045","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0172575","article-title":"Microvesicles released from fat-laden cells promote activation of hepatocellular NLRP3 inflammasome: A pro-inflammatory link between lipotoxicity and non-alcoholic steatohepatitis","volume":"12","author":"Cannito","year":"2017","journal-title":"PLoS One"},{"issue":"10213","key":"10.1016\/j.intimp.2025.114020_b0050","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1016\/S0140-6736(19)32517-6","article-title":"Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial","volume":"394","author":"Harrison","year":"2019","journal-title":"Lancet"},{"issue":"1","key":"10.1016\/j.intimp.2025.114020_b0055","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3350\/cmh.2022.0237","article-title":"Pathogenesis and treatment of non-alcoholic steatohepatitis and its fibrosis","volume":"29","author":"Lee","year":"2023","journal-title":"Clin. Mol. Hepatol."},{"issue":"10","key":"10.1016\/j.intimp.2025.114020_b0060","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1136\/gutjnl-2020-322509","article-title":"Sphingomyelin synthase 1 mediates hepatocyte pyroptosis to trigger non-alcoholic steatohepatitis","volume":"70","author":"Koh","year":"2021","journal-title":"Gut"},{"key":"10.1016\/j.intimp.2025.114020_b0065","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.lfs.2018.04.022","article-title":"Oleic acid protects saturated fatty acid mediated lipotoxicity in hepatocytes and rat of non-alcoholic steatohepatitis","volume":"203","author":"Chen","year":"2018","journal-title":"Life Sci."},{"issue":"1","key":"10.1016\/j.intimp.2025.114020_b0070","doi-asserted-by":"crossref","first-page":"11365","DOI":"10.1038\/s41598-018-29735-6","article-title":"Palmitate-induced lipotoxicity is crucial for the pathogenesis of nonalcoholic fatty liver disease in cooperation with gut-derived endotoxin","volume":"8","author":"Ogawa","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.intimp.2025.114020_b0075","doi-asserted-by":"crossref","DOI":"10.3389\/fnut.2022.952451","article-title":"Dietary fatty acids and risk of non-alcoholic steatohepatitis: A national study in the United States","volume":"9","author":"Lu","year":"2022","journal-title":"Front. Nutr."},{"key":"10.1016\/j.intimp.2025.114020_b0080","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.freeradbiomed.2019.05.029","article-title":"Lipidomic biomarkers and mechanisms of lipotoxicity in non-alcoholic fatty liver disease","volume":"144","author":"Svegliati-Baroni","year":"2019","journal-title":"Free Radic. Biol. Med."},{"issue":"2","key":"10.1016\/j.intimp.2025.114020_b0085","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jhep.2017.11.014","article-title":"Svegliati-Baroni, Lipotoxicity and the gut-liver axis in NASH pathogenesis","volume":"68","author":"Marra","year":"2018","journal-title":"J. Hepatol."},{"issue":"8","key":"10.1016\/j.intimp.2025.114020_b0090","doi-asserted-by":"crossref","first-page":"436","DOI":"10.4254\/wjh.v12.i8.436","article-title":"Lipidomics in non-alcoholic fatty liver disease","volume":"12","author":"Kartsoli","year":"2020","journal-title":"World J. Hepatol."},{"key":"10.1016\/j.intimp.2025.114020_b0095","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2022.115157","article-title":"Ceramide de novo synthesis in non-alcoholic fatty liver disease: Pathogenic mechanisms and therapeutic perspectives","volume":"202","author":"Yu","year":"2022","journal-title":"Biochem. Pharmacol."},{"issue":"10","key":"10.1016\/j.intimp.2025.114020_b0100","first-page":"1049","article-title":"Insulin resistance and neurodegeneration: roles of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis","volume":"10","author":"de la Monte","year":"2009","journal-title":"Curr. Opin. Invest. Drugs"},{"key":"10.1016\/j.intimp.2025.114020_b0105","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/978-3-319-48382-5_19","article-title":"Non-Alcoholic Fatty Liver Disease","volume":"960","author":"Engin","year":"2017","journal-title":"Advances in Experimental Medicine and Biology"},{"issue":"3","key":"10.1016\/j.intimp.2025.114020_b0110","doi-asserted-by":"crossref","DOI":"10.1002\/prp2.1094","article-title":"Novel oral SPT inhibitor CH5169356 inhibits hepatic stellate cell activation and ameliorates hepatic fibrosis in mouse models of non-alcoholic steatohepatitis (NASH)","volume":"11","author":"Hada","year":"2023","journal-title":"Pharmacol. Res. Perspect."},{"key":"10.1016\/j.intimp.2025.114020_b0115","doi-asserted-by":"crossref","first-page":"505","DOI":"10.3389\/fendo.2020.00505","article-title":"Too Much of a Good Thing? An Evolutionary Theory to Explain the Role of Ceramides in NAFLD","volume":"11","author":"Poss","year":"2020","journal-title":"Front Endocrinol (lausanne)"},{"issue":"3","key":"10.1016\/j.intimp.2025.114020_b0120","article-title":"A human liver chimeric mouse model for non-alcoholic fatty liver disease","volume":"3","author":"Bissig-Choisat","year":"2021","journal-title":"JHEP Rep."},{"key":"10.1016\/j.intimp.2025.114020_b0125","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2020.110076","article-title":"Gegen Qinlian Decoction abates nonalcoholic steatohepatitis associated liver injuries via anti-oxidative stress and anti-inflammatory response involved inhibition of toll-like receptor 4 signaling pathways","volume":"126","author":"Zhang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.intimp.2025.114020_b0130","doi-asserted-by":"crossref","first-page":"665","DOI":"10.3389\/fendo.2019.00665","article-title":"Inhibiting Ceramide Synthesis Attenuates Hepatic Steatosis and Fibrosis in Rats with Non-alcoholic Fatty Liver Disease","volume":"10","author":"Jiang","year":"2019","journal-title":"Front Endocrinol (lausanne)."},{"issue":"5633","key":"10.1016\/j.intimp.2025.114020_b0135","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1126\/science.1087262","article-title":"Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway","volume":"301","author":"Yamamoto","year":"2003","journal-title":"Science"},{"issue":"Suppl 1 0 1","key":"10.1016\/j.intimp.2025.114020_b0140","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/jgh.12019","article-title":"Toll-like receptors in alcoholic liver disease, non-alcoholic steatohepatitis and carcinogenesis","volume":"28","author":"Roh","year":"2013","journal-title":"J. Gastroenterol. Hepatol."},{"issue":"599","key":"10.1016\/j.intimp.2025.114020_b0145","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abe1692","article-title":"Hepatocyte TLR4 triggers inter-hepatocyte Jagged1\/Notch signaling to determine NASH-induced fibrosis","volume":"13","author":"Yu","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.intimp.2025.114020_b0150","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2024.117841","article-title":"Chaihu Guizhi Ganjiang Decoction attenuates nonalcoholic steatohepatitis by enhancing intestinal barrier integrity and ameliorating PPARalpha mediated lipotoxicity","volume":"326","author":"Wu","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.intimp.2025.114020_b0155","doi-asserted-by":"crossref","DOI":"10.1016\/j.cbi.2023.110461","article-title":"Chlorogenic acid ameliorated non-alcoholic steatohepatitis via alleviating hepatic inflammation initiated by LPS\/TLR4\/MyD88 signaling pathway","volume":"376","author":"Gu","year":"2023","journal-title":"Chem. Biol. Interact."}],"container-title":["International Immunopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576925000098?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576925000098?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T19:56:56Z","timestamp":1740599816000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1567576925000098"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":31,"alternative-id":["S1567576925000098"],"URL":"https:\/\/doi.org\/10.1016\/j.intimp.2025.114020","relation":{},"ISSN":["1567-5769"],"issn-type":[{"value":"1567-5769","type":"print"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"SFAs facilitates ceramide\u2019s de novo synthesis via TLR4 and intensifies hepatocyte lipotoxicity","name":"articletitle","label":"Article Title"},{"value":"International Immunopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.intimp.2025.114020","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"114020"}}