加巴能
导水管周围灰质
暴饮暴食
内分泌学
内科学
脂肪组织
肥胖
生物
神经科学
医学
中脑
中枢神经系统
受体
作者
Xiaomeng Wang,Xiaotong Wu,Hao Wu,Hanyang Xiao,Sijia Hao,Bingwei Wang,Chen Li,Katherin Bleymehl,Stefan G. Kauschke,Volker Mack,Boris Ferger,H. Klein,Ruimao Zheng,Shumin Duan,Hao Wang
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-11-03
卷期号:9 (44)
标识
DOI:10.1126/sciadv.adh2884
摘要
Overeating disorders largely contribute to worldwide incidences of obesity. Available treatments are limited. Here, we discovered that long-term chemogenetic activation of ventrolateral periaqueductal gray (vlPAG) GABAergic cells rescue obesity of high-fat diet–induced obesity (DIO) mice. This was associated with the recovery of enhanced mIPSCs, decreased food intake, increased energy expenditure, and inguinal white adipose tissue (iWAT) browning. In vivo calcium imaging confirmed vlPAG GABAergic suppression for DIO mice, with corresponding reduction in intrinsic excitability. Single-nucleus RNA sequencing identified transcriptional expression changes in GABAergic cell subtypes in DIO mice, highlighting Cacna2d1 as of potential importance. Overexpressing CACNA2D1 in vlPAG GABAergic cells of DIO mice rescued enhanced mIPSCs and calcium response, reversed obesity, and therefore presented here as a potential target for obesity treatment.
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