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.

中文翻译：

---

下丘脑中的葡萄糖依赖性促胰岛素多肽受体表达细胞调节食物摄入。

关于葡萄糖依赖性促胰岛素多肽 (GIP) 在肥胖中的作用的模糊性源于相互矛盾的报道，声称 GIP 受体 (GIPR) 激动和拮抗都是抑制体重增加的有效策略。为了能够识别和操作表达 Gipr (Gipr) 的细胞，我们创建了 Gipr-Cre 敲入小鼠。由于最近有报道称 GIPR 激动剂可以抑制食物摄入，我们旨在确定这种效应的中枢介质。正如 RNAscope 在小鼠和人类中所证实的那样，在下丘脑的弓状核、背内侧核和室旁核中鉴定了 Gipr 细胞。单细胞 RNA-seq 鉴定了下丘脑 Gipr 细胞簇，这些细胞表现出血管、神经胶质和神经元细胞的转录组特征，后者表达生长抑素，但很少表达阿片黑皮质素原或刺鼠相关肽。下丘脑 Gipr 细胞中 Gq-DREADD 的激活抑制了体内的食物摄入，这与伴随的 GLP1R 激活没有明显的叠加。这些数据将下丘脑 GIPR 确定为调节能量平衡的目标。