{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:22:56Z","timestamp":1785853376190,"version":"3.56.0"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T00:00:00Z","timestamp":1711756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Liver ischaemia\/reperfusion (I\/R) injury, which is an inevitable clinical problem of liver resection, liver transplantation and haemorrhagic shock. Fibroblast growth factor 21 (FGF21) was intimately coupled with multiple metabolic processes and proved to protect against apoptosis and inflammatory response in hepatocytes during hepatic I\/R injury. However, the regulatory mechanisms of FGF21 in hepatic I\/R injury remains unknown. Therefore, we hypothesize that FGF21 protects hepatic tissues from I\/R injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Blood samples were available from haemangiomas patients undergoing hepatectomy and murine liver I\/R model and used to further evaluate the serum levels of FGF21 both in humans and mice. We further explored the regulatory mechanisms of FGF21 in murine liver I\/R model by using FGF21\u2010knockout mice (FGF21\u2010KO mice) and FGF21\u2010overexpression transgenic mice (FGF21\u2010OE mice) fed a high\u2010fat or ketogenic diet.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results show that the circulating levels of FGF21 were robustly decreased after liver I\/R in both humans and mice. Silencing FGF21 expression with FGF21\u2010KO mice aggravates liver injury at 6\u2009h after 75\u2009min of partial liver ischaemia, while FGF21\u2010OE mice display alleviated hepatic I\/R injury and inflammatory response. Compared with chow diet mice, exogenous FGF21 decreases the levels of aminotransferase, histological changes, apoptosis and inflammatory response in hepatic I\/R injury treatment mice with a high\u2010fat diet. Meanwhile, ketogenic diet mice are not sensitive to hepatic I\/R injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The circulating contents of FGF21 are decreased during liver warm I\/R injury and exogenous FGF21 exerts hepatoprotective effects on hepatic I\/R injury. Thus, FGF21 regulates hepatic I\/R injury and may be a key therapeutic target.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15911","type":"journal-article","created":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T11:10:09Z","timestamp":1711797009000},"page":"1668-1679","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["FGF21 protects against ischaemia reperfusion injury in normal and fatty livers"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6508-508X","authenticated-orcid":false,"given":"Yong","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetts USA"},{"name":"Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Minimal Invasive Hepatic Surgery The First Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garima","family":"Singhal","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne S.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoqun","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Minimal Invasive Hepatic Surgery The First Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjun","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Minimal Invasive Hepatic Surgery The First Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Yin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of Minimal Invasive Hepatic Surgery The First Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Malvar","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imad","family":"Nasser","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie L.","family":"Mather","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleftheria","family":"Maratos\u2010Flier","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,30]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001411"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14091"},{"key":"e_1_2_14_4_1","first-page":"2910643","article-title":"Mechanism and therapies of oxidative stress\u2010mediated cell death in ischemia reperfusion injury","author":"Li H","year":"2018","journal-title":"Hindawi"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40008"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-2001"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021115-105339"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2017.08.001"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13023"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.10.039"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.07.044"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.02.012"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2017.08.004"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2019.113007"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14007"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13952"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.03.100"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-015-0077-2"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-015-3630-8"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2016.05.026"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148252"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2017.4564"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2009.01464.x"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2016.05.010"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.19927"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201300010"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.07.009"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.04.054"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00361.2010"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12072141"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-37198-y"},{"issue":"1","key":"e_1_2_14_32_1","first-page":"1","article-title":"Circulating fibroblast growth factor 21 is a sensitive biomarker for severe ischemia\/reperfusion injury in patients with liver transplantation","volume":"6","author":"Ye D","year":"2016","journal-title":"Sci Rep"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00101"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2019.02.013"},{"issue":"3","key":"e_1_2_14_35_1","first-page":"1684","article-title":"FGF21 attenuates hypoxia\u2010induced dysfunction and apoptosis in HPAECs through alleviating endoplasmic reticulum stress","volume":"42","author":"Chen A","year":"2018","journal-title":"Int J Mol Med"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.07.020"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2018.10.013"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701600104"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23606"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21675"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-0285.2012.01325.x"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.08.002"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.03.005"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14384-z"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.15911","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T04:29:11Z","timestamp":1718684951000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.15911"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,30]]},"references-count":43,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1111\/liv.15911"],"URL":"https:\/\/doi.org\/10.1111\/liv.15911","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,30]]},"assertion":[{"value":"2023-08-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}