Display options
Cite
Raptis DA, Limani P, Jang JH, et al. GPR120 on Kupffer cells mediates hepatoprotective effects of ω3-fatty acids. J Hepatol. 2013;60(3):625-32doi: 10.1016/j.jhep.2013.11.006.
Raptis, D. A., Limani, P., Jang, J. H., Ungethüm, U., Tschuor, C., Graf, R., Humar, B., & Clavien, P. A. (2014). GPR120 on Kupffer cells mediates hepatoprotective effects of ω3-fatty acids. Journal of hepatology, 60(3), 625-32. https://doi.org/10.1016/j.jhep.2013.11.006
Raptis, Dimitri Aristotle, et al. "GPR120 on Kupffer cells mediates hepatoprotective effects of ω3-fatty acids." Journal of hepatology vol. 60,3 (2014): 625-32. doi: https://doi.org/10.1016/j.jhep.2013.11.006
Raptis DA, Limani P, Jang JH, Ungethüm U, Tschuor C, Graf R, Humar B, Clavien PA. GPR120 on Kupffer cells mediates hepatoprotective effects of ω3-fatty acids. J Hepatol. 2014 Mar;60(3):625-32. doi: 10.1016/j.jhep.2013.11.006. Epub 2013 Nov 18. PMID: 24262133.
Copy Download .nbib Format: NLM
Share it on

J Hepatol. 2014 Mar;60(3):625-32. doi: 10.1016/j.jhep.2013.11.006. Epub 2013 Nov 18.

GPR120 on Kupffer cells mediates hepatoprotective effects of ω3-fatty acids.

Journal of hepatology

Dimitri Aristotle Raptis, Perparim Limani, Jae Hwi Jang, Udo Ungethüm, Christoph Tschuor, Rolf Graf, Bostjan Humar, Pierre-Alain Clavien

Affiliations

  1. Department of Surgery, Laboratory of the Swiss HPB Center, University Hospital of Zurich, Switzerland.
  2. Department of Surgery, Laboratory of the Swiss HPB Center, University Hospital of Zurich, Switzerland. Electronic address: [email protected].

PMID: 24262133 DOI: 10.1016/j.jhep.2013.11.006

Abstract

BACKGROUND & AIMS: Many of the beneficial effects of ω3-fatty acids (ω3FAs) are being attributed to their anti-inflammatory properties. In animal models, ω3FAs also protect from hepatic ischemia reperfusion injury (IRI), a significant cause of complications following liver surgery. Omegaven®, a clinical ω3FA-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 ω3FAs, mediating their anti-inflammatory effects. Here, we sought to investigate whether Omegaven® 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®.

RESULTS: GPR120 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.

CONCLUSIONS: These findings establish KC-GPR120 as a key mediator of Omegaven® effects and suggest GPR120 as a therapeutic target to mitigate inflammatory stress in liver.

Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Keywords: ALT; AST; Alanine transaminase; Aspartate transaminase; Fatty acids; G protein-coupled receptor 120; GPR120; IRI; KC; Kupffer cells; Liver; O3far1; Omega-3; ROS; Reperfusion injury; i.p.; i.v.; intra-peritoneal; intra-venous; ischemia reperfusion injury; omega-3 fatty acids; reactive oxygen species; ω3FAs

Substances

MeSH terms

Publication Types