- 作者：Dimitri Aristotle Raptis ; Perparim Limani ; Jae Hwi Jang ; Udo Ungeth眉m ; Christoph Tschuor ; Rolf Graf ; Bostjan Humar ; Pierre-Alain Clavien
- 关键词：ALT ; Alanine transaminase ; AST ; Aspartate transaminase ; GPR120 ; G protein-coupled receptor 120 ; i.p. ; intra-peritoneal ; i.v. ; intra-venous ; IRI ; ischemia reperfusion injury ; KC ; Kupffer cells ; ROS ; reactive oxygen species ; 蠅3FAs ; omega-3 fatty acids
- 刊名：Journal of Hepatology
- 出版年：March, 2014
- 年：2014
- 卷：60
- 期：3
- 页码：625-632
- 全文大小：1940 K
Background & Aims
Many of the beneficial effects of 蠅3-fatty acids (蠅3FAs) are being attributed to their anti-inflammatory properties. In animal models, 蠅3FAs also protect from hepatic ischemia reperfusion injury (IRI), a significant cause of complications following liver surgery. Omegaven庐, a clinical 蠅3FA-formulation, might counteract the exaggerated inflammatory response underlying IRI, but the according mechanisms are unresearched. Recently, GPR120 has been identified as a first receptor for 蠅3FAs, mediating their anti-inflammatory effects. Here, we sought to investigate whether Omegaven庐 protects from hepatic IRI through GPR120.Methods
Using a mouse model of liver IRI, we compared the effects of a GPR120 agonist with those of Omegaven庐.
Results
GPR120 in liver was located to Kupffer cells (KCs). Agonist and Omegaven庐 provided similar protection from IRI, which was abolished by clodronate-depletion of KCs or by pretreatment with an 伪Gpr120-siRNA. In vitro and in vivo, both agents dampened the NF魏B/JNK-mediated inflammatory response. Dampening was associated with an M1>M2 macrophage polarization shift as assessed by marker expression. In 伪Gpr120-siRNA-pretreated mice with or without ischemia, Omegaven庐 was no more able to promote M2 marker expression, indicating its anti-inflammatory properties are dependent on GPR120 in liver.
Conclusions
These findings establish KC-GPR120 as a key mediator of Omegaven庐 effects and suggest GPR120 as a therapeutic target to mitigate inflammatory stress in liver.