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Bitter taste cells in the ventricular walls of the murine brain regulate glucose homeostasis. 2023
Qiang Yu, and
Igor Gamayun, and
Philipp Wartenberg, and
Qian Zhang, and
Sen Qiao, and
Soumya Kusumakshi, and
Sarah Candlish, and
Viktoria Götz, and
Shuping Wen, and
Debajyoti Das, and
Amanda Wyatt, and
Vanessa Wahl, and
Fabien Ectors, and
Kathrin Kattler, and
Daniela Yildiz, and
Vincent Prevot, and
Markus Schwaninger, and
Gaetan Ternier, and
Paolo Giacobini, and
Philippe Ciofi, and
Timo D Müller, and
Ulrich Boehm
Department of Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany.
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.
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