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

被引：266

作者：

Adriaenssens, Alice E. ^{[1
]}

Biggs, Emma K. ^{[1
]}

Darwish, Tamana ^{[1
]}

Tadross, John ^{[1
]}

Sukthankar, Tanmay ^{[1
]}

Girish, Milind ^{[1
]}

Polex-Wolf, Joseph ^{[1
]}

Lam, Brain Y. ^{[1
]}

Zvetkova, Ilona ^{[1
]}

Pan, Warren ^{[1
]}

Chiarugi, Davide ^{[1
]}

Yeo, Giles S. H. ^{[1
]}

Blouet, Clemence ^{[1
]}

Gribble, Fiona M. ^{[1
]}

Reimann, Frank ^{[1
]}

机构：

[1] Addenbrookes Hosp, Wellcome Trust MRC Inst Metab Sci, Metab Res Labs, Hills Rd, Cambridge CB2 0QQ, England

来源：

CELL METABOLISM | 2019年 / 30卷 / 05期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

GASTRIC-INHIBITORY POLYPEPTIDE; GLUCAGON-LIKE PEPTIDE-1; BODY-WEIGHT; KNOCKOUT MICE; GIP; NEURONS; MOUSE; IDENTIFICATION; HETEROGENEITY; PHARMACOLOGY;

D O I：

10.1016/j.cmet.2019.07.013

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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-cellRNA-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.

引用

页码：987 / +

页数：16

共 54 条

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