Journal Article

Estrogen receptor-α expressing neurons in the ventrolateral VMH regulate glucose balance

Cai, Xing, Xu, Yong, Piyarathna, Badrajee, Wang, Julia, Xu, Pingwen, Zhao, Zhongming, Yang, Yongjie, Saito, Kenji, Chen, Rui, Khan, Sohaib A., Tong, Qingchun, He, Yanlin, Wang, Chunmei, Hyseni, Ilirjana, Xia, Yan, Qu, Na, Liu, Feng, Sun, Zheng, Robertson, Matthew, Coarfa, Cristian, Gao, Min, Yu, Kaifan, Yu, Meng

2020

Overview

Brain glucose-sensing neurons detect glucose fluctuations and prevent severe hypoglycemia, but mechanisms mediating functions of these glucose-sensing neurons are unclear. Here we report that estrogen receptor-α (ERα)-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH) can sense glucose fluctuations, being glucose-inhibited neurons (GI-ERα vlVMH ) or glucose-excited neurons (GE-ERα vlVMH ). Hypoglycemia activates GI-ERα vlVMH neurons via the anoctamin 4 channel, and inhibits GE-ERα vlVMH neurons through opening the ATP-sensitive potassium channel. Further, we show that GI-ERα vlVMH neurons preferentially project to the medioposterior arcuate nucleus of the hypothalamus (mpARH) and GE-ERα vlVMH neurons preferentially project to the dorsal Raphe nuclei (DRN). Activation of ERα vlVMH to mpARH circuit and inhibition of ERα vlVMH to DRN circuit both increase blood glucose. Thus, our results indicate that ERα vlVMH neurons detect glucose fluctuations and prevent severe hypoglycemia in mice. Glucose-sensing neurons are found in the ventromedial hypothalamic nucleus (VMH). Here the authors identify the role of estrogen receptor-α expressing neurons in the ventrolateral subdivision of the VMH in sensing hypoglycemia.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/91 / 631/378 / 631/443 / 64/110 / 692/163 / 9/74 / 9/97 / Animals / Arcuate nucleus / Chemoreception / Circuits / Detection / Electrophysiology / Endocrinology / Estrogen Receptor alpha - metabolism / Estrogens / Female / Fluctuations / Glucose / Glucose - metabolism / Humanities and Social Sciences / Hypoglycemia / Hypothalamus / Hypothalamus (ventromedial) / Mice / Mice, Transgenic / multidisciplinary / Neurons / Neurons - metabolism / Potassium / Raphe nuclei / Real-Time Polymerase Chain Reaction / Receptors / Science / Science (multidisciplinary)