{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:12:36Z","timestamp":1792098756278,"version":"4.4.0"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T00:00:00Z","timestamp":1584662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["19ZR1440200"],"award-info":[{"award-number":["19ZR1440200"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["2018MHZ044"],"award-info":[{"award-number":["2018MHZ044"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970684"],"award-info":[{"award-number":["31970684"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700510"],"award-info":[{"award-number":["81700510"]}],"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":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>NASH is one of the fastest growing liver diseases that leads to severe steatosis, inflammation and ultimately liver injury. However, the pathophysiological mechanisms of NASH remain unclear and pharmacological treatment against the disease is unavailable currently. Ferroptosis is a non\u2010apoptotic form of cell death induced by iron\u2010dependent lipid peroxidation. Since NASH progression is accompanied by massive lipid accumulation, which generates lipotoxic species, we investigated the role of ferroptosis in NASH progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Mice were fed on MCD\u2010diet to mimic NASH progression and gene expression in liver was analysed by RNA\u2010seq. The occurrence of hepatic ferroptosis was measured by lipid ROS level, electron microscopy and in vivo PI staining. The beneficial effects of ferroptosis inhibitors on NASH was evaluated by liver pathology analysis. The mechanism of lipid ROS induced lipid droplets\u00a0accumulation was investigated by in vitro cell culture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>RNA\u2010seq analysis suggested that elevated arachidonic acid metabolism promotes ferroptosis in MCD\u2010diet fed mouse livers, which was further demonstrated by lipid ROS accumulation, morphological change of mitochondria and increased cell death. Iron accumulation was detected in the liver and the serum of MCD\u2010fed mice. Scavenging of ferroptosis\u2010linked lipid peroxides reduced lipid accumulation both in vivo and in vitro. Importantly, ferroptosis inhibitors alleviated MCD\u2010diet induced inflammation, fibrogenesis and liver injury. Finally, lipid ROS promotes liver steatosis by boosting lipid droplets formation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results demonstrate an important role of ferroptosis in the progression of MCD\u2010diet induced NASH and suggest that ferroptosis may serve as a therapeutic target for NASH treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.14428","type":"journal-article","created":{"date-parts":[[2020,3,7]],"date-time":"2020-03-07T16:35:40Z","timestamp":1583598940000},"page":"1378-1394","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":259,"title":["Targeting ferroptosis alleviates methionine\u2010choline deficient (MCD)\u2010diet induced NASH by suppressing liver lipotoxicity"],"prefix":"10.1111","volume":"40","author":[{"given":"Xiaoya","family":"Li","sequence":"first","affiliation":[{"name":"Department of Endocrinology of the Fifth People\u2019s Hospital of Shanghai and the Molecular and Cell Biology Lab of the Institutes of Biomedical Sciences Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian\u2010Xiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of the Fifth People\u2019s Hospital of Shanghai and the Molecular and Cell Biology Lab of the Institutes of Biomedical Sciences Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of the Fifth People\u2019s Hospital of Shanghai and the Molecular and Cell Biology Lab of the Institutes of Biomedical Sciences Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of the Fifth People\u2019s Hospital of Shanghai and the Molecular and Cell Biology Lab of the Institutes of Biomedical Sciences Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiange","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of the Fifth People\u2019s Hospital of Shanghai and the Molecular and Cell Biology Lab of the Institutes of Biomedical Sciences Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shufei","family":"Zang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology of the Fifth People\u2019s Hospital of Shanghai and the Molecular and Cell Biology Lab of the Institutes of Biomedical Sciences Fudan University Shanghai 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