GABAergic disinhibition from the BNST to PNOC ARC neurons promotes HFD-induced hyperphagia.

Autor:	Sotelo-Hitschfeld T; Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany; Policlinic for Endocrinology, Diabetes, and Preventive Medicine (PEDP), University Hospital Cologne, Kerpener Strasse 26, 50924 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany., Minère M; Policlinic for Endocrinology, Diabetes, and Preventive Medicine (PEDP), University Hospital Cologne, Kerpener Strasse 26, 50924 Cologne, Germany; Synaptic Transmission in Energy Homeostasis Research Group, Max Planck Institute for Metabolism Research, Cologne, Germany., Klemm P; Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany; Policlinic for Endocrinology, Diabetes, and Preventive Medicine (PEDP), University Hospital Cologne, Kerpener Strasse 26, 50924 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany., Borgmann D; Synaptic Transmission in Energy Homeostasis Research Group, Max Planck Institute for Metabolism Research, Cologne, Germany; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Wnuk-Lipinski D; Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany; Policlinic for Endocrinology, Diabetes, and Preventive Medicine (PEDP), University Hospital Cologne, Kerpener Strasse 26, 50924 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany., Jais A; Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany; Policlinic for Endocrinology, Diabetes, and Preventive Medicine (PEDP), University Hospital Cologne, Kerpener Strasse 26, 50924 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany., Jia X; Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany; Policlinic for Endocrinology, Diabetes, and Preventive Medicine (PEDP), University Hospital Cologne, Kerpener Strasse 26, 50924 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany., Corneliussen S; Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany; Institute of Zoology, Faculty of Mathematics and Natural Sciences, University of Cologne, Cologne, Germany., Kloppenburg P; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany; Institute of Zoology, Faculty of Mathematics and Natural Sciences, University of Cologne, Cologne, Germany., Fenselau H; Policlinic for Endocrinology, Diabetes, and Preventive Medicine (PEDP), University Hospital Cologne, Kerpener Strasse 26, 50924 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany; Synaptic Transmission in Energy Homeostasis Research Group, Max Planck Institute for Metabolism Research, Cologne, Germany. Electronic address: henning.fenselau@sf.mpg.de., Brüning JC; Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Cologne, Germany; National Center for Diabetes Research (DZD), Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany. Electronic address: bruening@sf.mpg.de.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Jun 25; Vol. 43 (6), pp. 114343. Date of Electronic Publication: 2024 Jun 11.
DOI:	10.1016/j.celrep.2024.114343
Abstrakt:	Activation of prepronociceptin (PNOC)-expressing neurons in the arcuate nucleus (ARC) promotes high-fat-diet (HFD)-induced hyperphagia. In turn, PNOC ARC neurons can inhibit the anorexic response of proopiomelanocortin (POMC) neurons. Here, we validate the necessity of PNOC ARC activity for HFD-induced inhibition of POMC neurons in mice and find that PNOC ARC -neuron-dependent inhibition of POMC neurons is mediated by gamma-aminobutyric acid (GABA) release. When monitoring individual PNOC ARC neuron activity via Ca 2+ imaging, we find a subpopulation of PNOC ARC neurons that is inhibited upon gastrointestinal calorie sensing and disinhibited upon HFD feeding. Combining retrograde rabies tracing and circuit mapping, we find that PNOC neurons from the bed nucleus of the stria terminalis (PNOC BNST ) provide inhibitory input to PNOC ARC neurons, and this inhibitory input is blunted upon HFD feeding. This work sheds light on how an increase in caloric content of the diet can rewire a neuronal circuit, paving the way to overconsumption and obesity development. Competing Interests: Declaration of interests J.C.B. is a cofounder of Cerapeutix and has received research funding through collaborations with Sanofi Aventis and Novo Nordisk, Inc. He also consulted for Eli Lilly and Company and Novo Nordisk, all of which did not affect the content of this article. (Copyright © 2024. Published by Elsevier Inc.)
Databáze:	MEDLINE
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