Glucose; Mice; Animals; Brain; Signal Transduction; Homeostasis; Taste/physiology; Taste Buds; General Physics and Astronomy; General Biochemistry, Genetics and Molecular Biology; General Chemistry; Multidisciplinary
Abstract :
[en] 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.
Yu, Qiang; Department of Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany
Gamayun, Igor ; Department of Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany
Wartenberg, Philipp; Department of Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany
Zhang, Qian; Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany, German Center for Diabetes Research (DZD), Neuherberg, Germany
Qiao, Sen ; Department of Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany
Kusumakshi, Soumya; Department of Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany
Candlish, Sarah; Department of Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany
Götz, Viktoria; Department of Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany
Wen, Shuping; Department of Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany
Das, Debajyoti; Department of Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany
Wyatt, Amanda ; Department of Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany
Wahl, Vanessa ; Department of Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany
Ectors, Fabien ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Kattler, Kathrin ; Department of Genetics, Saarland University, Saarbrücken, Germany
Yildiz, Daniela; Department of Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany
Prevot, Vincent ; Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Postnatal Brain, Lille Neuroscience & Cognition, UMR-S1172, Lille, France
Schwaninger, Markus ; Institute for Experimental and Clinical Pharmacology and Toxicology, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany
Ternier, Gaetan ; Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Postnatal Brain, Lille Neuroscience & Cognition, UMR-S1172, Lille, France
Giacobini, Paolo ; Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Postnatal Brain, Lille Neuroscience & Cognition, UMR-S1172, Lille, France
Ciofi, Philippe; Neurocentre Magendie - INSERM Unit 1215, University of Bordeaux, Bordeaux, France
Müller, Timo D ; Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany, German Center for Diabetes Research (DZD), Neuherberg, Germany
Boehm, Ulrich ; Department of Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany. ulrich.boehm@uks.eu
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