PNOC ARC Neurons Promote Hyperphagia and Obesity upon High-Fat-Diet Feeding.

Autor:	Jais A; Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany; Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), 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, Cologne, Germany., Paeger L; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Institute for Zoology, Biocenter, University of Cologne, Cologne, Germany., Sotelo-Hitschfeld T; Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany; Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), 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, Cologne, Germany., Bremser S; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Institute for Zoology, Biocenter, University of Cologne, Cologne, Germany., Prinzensteiner M; Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany; Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), 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, Cologne, Germany., Klemm P; Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany; Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), 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, Cologne, Germany., Mykytiuk V; Neuronal Circuits and Behaviour Group, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany., Widdershooven PJM; Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany; Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), 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, Cologne, Germany., Vesting AJ; Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), 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, Cologne, Germany; Obesity and Cancer Group, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany., Grzelka K; Synaptic Transmission in Energy Homeostasis Group, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany., Minère M; Synaptic Transmission in Energy Homeostasis Group, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany., Cremer AL; Multimodal Imaging of Brain Metabolism Group, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany., Xu J; Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA., Korotkova T; Neuronal Circuits and Behaviour Group, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany., Lowell BB; Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02215, USA., Zeilhofer HU; Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland., Backes H; Multimodal Imaging of Brain Metabolism Group, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany., Fenselau H; Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), University Hospital Cologne, Kerpener Strasse 26, 50924 Cologne, Germany; Synaptic Transmission in Energy Homeostasis Group, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany., Wunderlich FT; Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), 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, Cologne, Germany; Obesity and Cancer Group, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany., Kloppenburg P; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Institute for Zoology, Biocenter, University of Cologne, Cologne, Germany. Electronic address: peter.kloppenburg@uni-koeln.de., Brüning JC; Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany; Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP), 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, Cologne, Germany. Electronic address: bruening@sf.mpg.de.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2020 Jun 17; Vol. 106 (6), pp. 1009-1025.e10. Date of Electronic Publication: 2020 Apr 16.
DOI:	10.1016/j.neuron.2020.03.022
Abstrakt:	Calorie-rich diets induce hyperphagia and promote obesity, although the underlying mechanisms remain poorly defined. We find that short-term high-fat-diet (HFD) feeding of mice activates prepronociceptin (PNOC)-expressing neurons in the arcuate nucleus of the hypothalamus (ARC). PNOC ARC neurons represent a previously unrecognized GABAergic population of ARC neurons distinct from well-defined feeding regulatory AgRP or POMC neurons. PNOC ARC neurons arborize densely in the ARC and provide inhibitory synaptic input to nearby anorexigenic POMC neurons. Optogenetic activation of PNOC ARC neurons in the ARC and their projections to the bed nucleus of the stria terminalis promotes feeding. Selective ablation of these cells promotes the activation of POMC neurons upon HFD exposure, reduces feeding, and protects from obesity, but it does not affect food intake or body weight under normal chow consumption. We characterize PNOC ARC neurons as a novel ARC neuron population activated upon palatable food consumption to promote hyperphagia. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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