Estrogen Receptor-α Expressing Neurons in the Ventrolateral VMH Regulate Glucose Balance

Authors

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

Publication Date

5-1-2020

Journal

Nature Communications

DOI

10.1038/s41467-020-15982-7

PMID

32358493

PMCID

PMC7195451

PubMedCentral® Posted Date

5-1-2020

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Electrophysiology, Endocrinology, Estrogen Receptor alpha, Female, Glucose, Mice, Mice, Transgenic, Neurons, Real-Time Polymerase Chain Reaction, Neuroscience, Physiology

Abstract

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-ERαvlVMH) or glucose-excited neurons (GE-ERαvlVMH). Hypoglycemia activates GI-ERαvlVMH neurons via the anoctamin 4 channel, and inhibits GE-ERαvlVMH neurons through opening the ATP-sensitive potassium channel. Further, we show that GI-ERαvlVMH neurons preferentially project to the medioposterior arcuate nucleus of the hypothalamus (mpARH) and GE-ERαvlVMH neurons preferentially project to the dorsal Raphe nuclei (DRN). Activation of ERαvlVMH to mpARH circuit and inhibition of ERαvlVMH to DRN circuit both increase blood glucose. Thus, our results indicate that ERαvlVMH neurons detect glucose fluctuations and prevent severe hypoglycemia in mice.