Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids
Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids
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DOI：
10.1016/s0006-291x(03)00488-1
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发表时间：
2003-04-18
影响因子：
3.1
通讯作者：
Olde, B
中科院分区：
文献类型：
--
作者：
Nilsson, NE;Kotarsky, K;Olde, B
短链脂肪酸（SCFA）长期以来一直被认为对血液白细胞产生细胞效应。乙酸盐、丙酸盐和丁酸盐代表最有能力的SCFA，诱导钙动员，随后调节免疫系统中的白细胞功能。我们已经克隆了先前描述的假定孤儿G蛋白偶联受体GPR43，并在功能上鉴定了SCFA作为活化配体。发现乙酸盐和丙酸盐是两种最有效的配体，尽管丁酸盐、甲酸盐和戊酸盐（以这种效力顺序）也能够诱导受体活化。人类和小鼠受体同源物被发现共享相同的配体激活模式。这一发现，以及小鼠和人类同源物之间高度的氨基酸序列相似性，表明进化保守的功能。在配体刺激后，受体在重组系统以及人粒细胞中动员细胞内钙。我们发现人类基因主要在外周血白细胞中表达，在较小程度上，在脾脏中。我们建议将游离脂肪酸激活的第二种受体命名为FFA（2）R。首先描述的FFAR，现在被命名为FFA（1）R，被中长链游离脂肪酸激活。(C)2003 Elsevier Science（美国）。All rights reserved.
Short-chain fatty acids (SCFAs) have long been known to exert cellular effects on blood leukocytes. Acetate, propionate, and butyrate represent the most capable SCFA, inducing calcium mobilization which subsequently regulates leukocyte function in the immune system. We have cloned the previously described putative orphan G-protein coupled receptor, GPR43, and have functionally identified SCFA as the activating ligands. Acetate and propionate were found to be the two most potent ligands, although butyrate, formate, and valerate (in this order of potency) also were able to induce receptor activation. Both the human and mouse receptor homologues were found to share the same pattern of ligand activation. This finding, together with a high degree of amino acid sequence similarity between the mouse and human homologues, indicates an evolutionary conserved function. Upon ligand stimulation, the receptor mobilized intracellular calcium in both a recombinant system as well as in human granulocytes. We found the human gene to be predominantly expressed in peripheral blood leukocytes and, to a lesser extent, in spleen. We suggest the designation FFA(2)R to this second receptor activated by free fatty acids. The first-described FFAR, now named FFA(1)R, is activated by medium- to long-chain free fatty acids. (C) 2003 Elsevier Science (USA). All rights reserved.