کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6104234 | 1211136 | 2014 | 8 صفحه PDF | دانلود رایگان |
Background & AimsMany of the beneficial effects of Ï3-fatty acids (Ï3FAs) are being attributed to their anti-inflammatory properties. In animal models, Ï3FAs also protect from hepatic ischemia reperfusion injury (IRI), a significant cause of complications following liver surgery. Omegaven®, a clinical Ï3FA-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 Ï3FAs, mediating their anti-inflammatory effects. Here, we sought to investigate whether Omegaven® protects from hepatic IRI through GPR120.MethodsUsing a mouse model of liver IRI, we compared the effects of a GPR120 agonist with those of Omegaven®.ResultsGPR120 in liver was located to Kupffer cells (KCs). Agonist and Omegaven® provided similar protection from IRI, which was abolished by clodronate-depletion of KCs or by pretreatment with an αGpr120-siRNA. In vitro and in vivo, both agents dampened the NFκB/JNK-mediated inflammatory response. Dampening was associated with an M1>M2 macrophage polarization shift as assessed by marker expression. In αGpr120-siRNA-pretreated mice with or without ischemia, Omegaven® was no more able to promote M2 marker expression, indicating its anti-inflammatory properties are dependent on GPR120 in liver.ConclusionsThese findings establish KC-GPR120 as a key mediator of Omegaven® effects and suggest GPR120 as a therapeutic target to mitigate inflammatory stress in liver.
Journal: Journal of Hepatology - Volume 60, Issue 3, March 2014, Pages 625-632