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研究鉴定出调控食物摄入的神经细胞
2019-08-26 14:21

英国剑桥艾登布鲁克医院Frank Reimann研究组和Fiona M. Gribble研究组合作发现,下丘脑中葡萄糖依赖的促胰岛素多肽受体表达细胞参与调节食物摄入。这一研究成果于2019年8月22日在线发表在国际学术期刊《细胞—代谢》上。

为了能够鉴定和操控表达Gipr的细胞,研究人员构建了Gipr-Cre敲入小鼠。由于最近报道GIPR激动剂可抑制食物摄入,研究人员的目的是确定这种效应的中枢调节者。在小鼠和人的RNAscope实验中证实,在下丘脑的弓形、背内侧和室旁核中鉴定出Gipr细胞。单细胞RNA-seq鉴定出下丘脑Gipr细胞团,其表现出血管、神经胶质和神经元细胞的转录组学特征,后者表达生长抑素,但几乎没有阿片促黑素皮质素原或刺鼠相关肽。下丘脑Gipr细胞中Gq-DREADD的激活抑制了食物摄入,这与伴随的GLP1R激活不太相关。这些数据表明,下丘脑的GIPR是调节能量平衡的靶标。

研究人员表示,葡萄糖依赖性促胰岛素多肽(GIP)在肥胖中作用的不确定性源于相互矛盾的报道,这些报道声称GIP受体(GIPR)激动和拮抗作用均是抑制体重增加的有效策略。

附:英文原文

Title: Glucose-Dependent Insulinotropic Polypeptide Receptor-Expressing Cells in the Hypothalamus Regulate Food Intake

Author: Alice E. Adriaenssens 2,Emma K. Biggs,Tamana Darwish,John Tadross,Tanmay Sukthankar,Milind Girish,Joseph Polex-Wolf,Brain Y. Lam,Ilona Zvetkova,Warren Pan,Davide Chiarugi,Giles S.H. Yeo,Clemence Blouet,Fiona M. Gribble,Frank Reimann

Issue&Volume: 22 August 2019

Abstract: Ambiguity regarding the role of glucose-dependent insulinotropic polypeptide (GIP) in obesity arises from conflicting reports asserting that both GIP receptor (GIPR) agonism and antagonism are effective strategies for inhibiting weight gain. To enable identification and manipulation of Gipr-expressing (Gipr) cells, we created Gipr-Cre knockin mice. As GIPR-agonists have recently been reported to suppress food intake, we aimed to identify central mediators of this effect. Gipr cells were identified in the arcuate, dorsomedial, and paraventricular nuclei of the hypothalamus, as confirmed by RNAscope in mouse and human. Single-cell RNA-seq identified clusters of hypothalamic Gipr cells exhibiting transcriptomic signatures for vascular, glial, and neuronal cells, the latter expressing somatostatin but little pro-opiomelanocortin or agouti-related peptide. Activation of Gq-DREADDs in hypothalamic Gipr cells suppressed food intake in vivo, which was not obviously additive with concomitant GLP1R activation. These data identify hypothalamic GIPR as a target for the regulation of energy balance.

DOI: https://doi.org/10.1016/j.cmet.2019.07.013

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30386-9#

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:31.373
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx


本期文章:《细胞—代谢》:Online/在线发表

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