FGF21 modulates immunometabolic homeostasis via the ALOX15/15-HETE axis in early liver graft injury

Xinyu Yang, Hao Chen, Wei Shen, Yuanming Chen, Zuyuan Lin, Jianyong Zhuo, Shuai Wang, Modan Yang, Huigang Li, Chiyu He, Xuanyu Zhang, Zhihang Hu, Zhengxing Lian, Mengfan Yang, Rui Wang, Changbiao Li, Binhua Pan, Li Xu, Jun Chen, Xuyong Wei, Qiang Wei, Haiyang Xie, Shusen Zheng, Di Lu () and Xiao Xu ()
Additional contact information
Xinyu Yang: Hangzhou First People’s Hospital
Hao Chen: Zhejiang University School of Medicine
Wei Shen: Zhejiang University School of Medicine
Yuanming Chen: Zhejiang University School of Medicine
Zuyuan Lin: Hangzhou First People’s Hospital
Jianyong Zhuo: Hangzhou First People’s Hospital
Shuai Wang: Hangzhou First People’s Hospital
Modan Yang: Zhejiang University School of Medicine
Huigang Li: Zhejiang University School of Medicine
Chiyu He: Zhejiang University School of Medicine
Xuanyu Zhang: Zhejiang University School of Medicine
Zhihang Hu: Zhejiang University School of Medicine
Zhengxing Lian: Hangzhou First People’s Hospital
Mengfan Yang: Qilu Hospital of Shandong University
Rui Wang: Zhejiang University Medical Center
Changbiao Li: Hangzhou Medical College
Binhua Pan: Hangzhou First People’s Hospital
Li Xu: Zhejiang University School of Medicine
Jun Chen: Hangzhou Medical College
Xuyong Wei: Hangzhou First People’s Hospital
Qiang Wei: Hangzhou Medical College
Haiyang Xie: NHC Key Laboratory of Combined Multi-organ Transplantation
Shusen Zheng: Zhejiang University School of Medicine
Di Lu: Hangzhou Medical College
Xiao Xu: Hangzhou Medical College

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Fibroblast growth factor 21 (FGF21) is essential for modulating hepatic homeostasis, but the impact of FGF21 on liver graft injury remains uncertain. Here, we show that high FGF21 levels in liver graft and serum are associated with improved graft function and survival in liver transplantation (LT) recipients. FGF21 deficiency aggravates early graft injury and activates arachidonic acid metabolism and regional inflammation in male mouse models of hepatic ischemia/reperfusion (I/R) injury and orthotopic LT. Mechanistically, FGF21 deficiency results in abnormal activation of the arachidonate 15-lipoxygenase (ALOX15)/15-hydroxy eicosatetraenoic acid (15-HETE) pathway, which triggers a cascade of innate immunity-dominated pro-inflammatory responses in grafts. Notably, the modulating role of FGF21/ALOX15/15-HETE pathway is more significant in steatotic livers. In contrast, pharmacological administration of recombinant FGF21 effectively protects against hepatic I/R injury. Overall, our study reveals the regulatory mechanism of FGF21 and offers insights into its potential clinical application in early liver graft injury after LT.

Date: 2024
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-52379-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52379-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-52379-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().