GPR84-mediated signal transduction affects metabolic function by promoting brown adipocyte activity.
GPR84-mediated signal transduction affects metabolic function by promoting brown adipocyte activity.
复制标题
GPR84介导的信号转导通过促进棕色脂肪细胞活性影响代谢功能。
DOI：
10.1172/jci168992
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发表时间：
2023-12-15
期刊：
影响因子：
--
通讯作者：
Oh DY
中科院分区：
文献类型：
--
作者：
Sun XN;An YA;Paschoal VA;de Souza CO;Wang MY;Vishvanath L;Bueno LM;Cobb AS;Nieto Carrion JA;Ibe ME;Li C;Kidd HA;Chen S;Li W;Gupta RK;Oh DY
G蛋白偶联受体84(GPR84)是一种中链脂肪酸受体，因其可能参与一系列代谢条件而引起人们的关注。然而，这种效应背后的确切机制仍然难以捉摸。我们的研究揭示了GPR84的关键作用，揭示了它在棕色脂肪组织(BAT)中的强劲表达和功能意义。缺乏GPR84的小鼠表现出BAT中脂肪积累增加，使它们更容易受到寒冷的影响，并且与WT对应的小鼠相比，BAT活性降低。我们对来自GPR84-KO小鼠的原代棕色脂肪细胞进行的体外实验显示，生热基因的表达减少，氧气消耗减少。此外，应用GPR84激动剂6-正辛基氨基尿嘧啶(6-非统)可抵消这些效应，有效地恢复棕色脂肪细胞的活性。这些令人信服的体内和体外发现汇聚在一起，强调线粒体功能障碍是GPR84-KO小鼠BAT异常的主要原因。GPR84的激活诱导了细胞内钙离子水平的增加，从而复杂地影响了线粒体的呼吸。通过调节线粒体钙水平和呼吸作用，GPR84作为一种有效的分子参与了BAT的活动。这些发现表明，GPR84是一个潜在的治疗靶点，以振兴BAT和改善代谢紊乱。
The G protein–coupled receptor 84 (GPR84), a medium-chain fatty acid receptor, has garnered attention because of its potential involvement in a range of metabolic conditions. However, the precise mechanisms underlying this effect remain elusive. Our study has shed light on the pivotal role of GPR84, revealing its robust expression and functional significance within brown adipose tissue (BAT). Mice lacking GPR84 exhibited increased lipid accumulation in BAT, rendering them more susceptible to cold exposure and displaying reduced BAT activity compared with their WT counterparts. Our in vitro experiments with primary brown adipocytes from GPR84-KO mice revealed diminished expression of thermogenic genes and reduced O2 consumption. Furthermore, the application of the GPR84 agonist 6-n-octylaminouracil (6-OAU) counteracted these effects, effectively reinstating the brown adipocyte activity. These compelling in vivo and in vitro findings converge to highlight mitochondrial dysfunction as the primary cause of BAT anomalies in GPR84-KO mice. The activation of GPR84 induced an increase in intracellular Ca2+ levels, which intricately influenced mitochondrial respiration. By modulating mitochondrial Ca2+ levels and respiration, GPR84 acts as a potent molecule involved in BAT activity. These findings suggest that GPR84 is a potential therapeutic target for invigorating BAT and ameliorating metabolic disorders.
影响因子：
3.7
作者：
Lin DC;Zhang J;Zhuang R;Li F;Nguyen K;Chen M;Tran T;Lopez E;Lu JY;Li XN;Tang L;Tonn GR;Swaminath G;Reagan JD;Chen JL;Tian H;Lin YJ;Houze JB;Luo J
通讯作者：
Luo J