Bitter taste cells in the ventricular walls of the murine brain regulate glucose homeostasis
Qiang Yu, Igor Gamayun, Philipp Wartenberg, Qian Zhang, Sen Qiao, Soumya Kusumakshi, Sarah Candlish, Viktoria Götz, Shuping Wen, Debajyoti Das, Amanda Wyatt, Vanessa Wahl, Fabien Ectors, Kathrin Kattler, Daniela Yildiz, Vincent Prévot, Markus Schwaninger, Gaëtan Ternier, Paolo Giacobini, Philippe Ciofi, Timo D. Müller, Ulrich Boehm
Abstract
The median eminence (ME) is a circumventricular organ at the base of the brain that controls body homeostasis. Tanycytes are its specialized glial cells that constitute the ventricular walls and regulate different physiological states, however individual signaling pathways in these cells are incompletely understood. Here, we identify a functional tanycyte subpopulation that expresses key taste transduction genes including bitter taste receptors, the G protein gustducin and the gustatory ion channel TRPM5 (M5). M5 tanycytes have access to blood-borne cues via processes extended towards diaphragmed endothelial fenestrations in the ME and mediate bidirectional communication between the cerebrospinal fluid and blood. This subpopulation responds to metabolic signals including leptin and other hormonal cues and is transcriptionally reprogrammed upon fasting. Acute M5 tanycyte activation induces insulin secretion and acute diphtheria toxin-mediated M5 tanycyte depletion results in impaired glucose tolerance in diet-induced obese mice. We provide a cellular and molecular framework that defines how bitter taste cells in the ME integrate chemosensation with metabolism.