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 Prevot, Markus Schwaninger, Gaetan Ternier, Paolo Giacobini, Philippe Ciofi, Timo D. Müller and Ulrich Boehm ()
Additional contact information
Qiang Yu: Center for Molecular Signaling (PZMS), Saarland University School of Medicine
Igor Gamayun: Center for Molecular Signaling (PZMS), Saarland University School of Medicine
Philipp Wartenberg: Center for Molecular Signaling (PZMS), Saarland University School of Medicine
Qian Zhang: Helmholtz Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany; German Center for Diabetes Research (DZD)
Sen Qiao: Center for Molecular Signaling (PZMS), Saarland University School of Medicine
Soumya Kusumakshi: Center for Molecular Signaling (PZMS), Saarland University School of Medicine
Sarah Candlish: Center for Molecular Signaling (PZMS), Saarland University School of Medicine
Viktoria Götz: Center for Molecular Signaling (PZMS), Saarland University School of Medicine
Shuping Wen: Center for Molecular Signaling (PZMS), Saarland University School of Medicine
Debajyoti Das: Center for Molecular Signaling (PZMS), Saarland University School of Medicine
Amanda Wyatt: Center for Molecular Signaling (PZMS), Saarland University School of Medicine
Vanessa Wahl: Center for Molecular Signaling (PZMS), Saarland University School of Medicine
Fabien Ectors: Liège University
Kathrin Kattler: Saarland University
Daniela Yildiz: Center for Molecular Signaling (PZMS), Saarland University School of Medicine
Vincent Prevot: Laboratory of Development and Plasticity of the Postnatal Brain, Lille Neuroscience & Cognition, UMR-S1172
Markus Schwaninger: Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck
Gaetan Ternier: Laboratory of Development and Plasticity of the Postnatal Brain, Lille Neuroscience & Cognition, UMR-S1172
Paolo Giacobini: Laboratory of Development and Plasticity of the Postnatal Brain, Lille Neuroscience & Cognition, UMR-S1172
Philippe Ciofi: Neurocentre Magendie - INSERM Unit 1215, University of Bordeaux
Timo D. Müller: Helmholtz Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany; German Center for Diabetes Research (DZD)
Ulrich Boehm: Center for Molecular Signaling (PZMS), Saarland University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-37099-3

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