LGR4 is essential for R-spondin1-mediated suppression of food intake via pro-opiomelanocortin
LGR4 is essential for R-spondin1-mediated suppression of food intake via pro-opiomelanocortin
复制标题
DOI：
10.1080/09168451.2019.1591266
复制
发表时间：
2019-03-29
影响因子：
1.6
通讯作者：
Nishimori, Katsuhiko
中科院分区：
文献类型：
--
作者：
Otsuka, Ayano;Jinguji, Ayana;Nishimori, Katsuhiko
富含亮氨酸重复的G蛋白偶联受体4（LGR 4）通过结合其配体R-spondins激活后抑制食物摄入。我们研究了R-spondin 1在区域特异性Lgr 4基因敲除（LGR 4 cKO）小鼠模型中抑制食物摄入的机制，该模型通过使用Lgr 4（fx/fx）小鼠结合AAV-Cre载体感染在弓状核（ARC）中缺失Lgr 4基因产生。在R-spondin 1给药后，与接受载体的对照小鼠相比，LGR 4 cKO小鼠没有表现出食欲抑制。在LGR 4 cKO小鼠的ARC中，Pomc mRNA表达降低，导致摄食量抑制。另一方面，神经元特异性LGR 4 KO小鼠在Pomc表达方面没有表现出差异，并且在突变小鼠的ARC中没有观察到结构差异。这些结果表明，LGR 4是该机制的重要组成部分，在小鼠ARC神经元中诱导Pomc基因表达R-spondin 1，从而调节摄食行为。
Leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4) suppresses food intake after its activation by binding of its ligands, R-spondins. We investigated the mechanism of food intake suppression by R-spondin1 in a region-specific Lgr4 gene knockout (LGR4 cKO) mouse model, generated by deletion of the Lgr4 gene in arcuate nucleus (ARC) using Lgr4(fx/fx) mice combined with infection of an AAV-Cre vector. After R-spondin1 administration, LGR4 cKO mice didn't exhibit a suppressed appetite, compared to that in control mice, which received a vehicle. In ARC of LGR4 cKO mice, Pomc mRNA expression was reduced, leading to suppressed food intake. On the other hand, neurons-specific LGR4 KO mice exhibited no differences in Pomc expression, and no structural differences were observed in the ARC of mutant mice. These results suggest that LGR4 is an essential part of the mechanism, inducing Pomc gene expression with R-spondin1 in ARC neurons in mice, thereby regulating feeding behavior.