GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects.

GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects.
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DOI:
10.1016/j.cell.2010.07.041
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发表时间:
2010-09-03
期刊:
影响因子:
64.5
通讯作者:
Olefsky JM
Olefsky JM
中科院分区:
生物学1区
文献类型:
--
作者:
Oh DY;Talukdar S;Bae EJ;Imamura T;Morinaga H;Fan W;Li P;Lu WJ;Watkins SM;Olefsky JM

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ω-3脂肪酸(ω-3 FAs)、DHA和EPA具有抗炎作用,但其机制尚不清楚。这里我们展示了G蛋白偶联受体120 (GPR120)作为ω-3 FA受体/传感器。ω-3脂肪酸或化学激动剂刺激GPR120可在单核细胞RAW 264.7细胞和原代腹腔巨噬细胞中产生广泛的抗炎作用。GPR120基因敲除后,这些影响均消失。由于慢性巨噬细胞介导的组织炎症是肥胖胰岛素抵抗的关键机制,我们给肥胖WT和GPR120基因敲除小鼠喂食高脂肪饮食,并添加或不添加ω-3脂肪酸。ω-3 FA处理能抑制WT小鼠的炎症反应,增强全身胰岛素敏感性,但对GPR120敲除小鼠无影响。综上所述,GPR120是一种功能性ω-3 FA受体/传感器,通过抑制巨噬细胞诱导的组织炎症,在体内介导有效的胰岛素增敏和抗糖尿病作用。
Omega-3 fatty acids (ω-3 FAs), DHA and EPA, exert anti-inflammatory effects, but the mechanisms are poorly understood. Here we show that the G protein-coupled receptor 120 (GPR120) functions as an ω-3 FA receptor/sensor. Stimulation of GPR120 with ω-3 FAs or a chemical agonist causes broad anti-inflammatory effects in monocytic RAW 264.7 cells and in primary intraperitoneal macrophages. All of these effects are abrogated by GPR120 knockdown. Since chronic macrophage-mediated tissue inflammation is a key mechanism for insulin resistance in obesity, we fed obese WT and GPR120 knockout mice a high fat diet with or without ω-3 FA supplementation. The ω-3 FA treatment inhibited inflammation and enhanced systemic insulin sensitivity in WT mice, but was without effect in GPR120 knockout mice. In conclusion, GPR120 is a functional ω-3 FA receptor/sensor and mediates potent insulin sensitizing and anti-diabetic effects in vivo by repressing macrophage-induced tissue inflammation.
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