Functional heterogeneity of POMC neurons relies on mTORC1 signaling
| Autor: | Nicolas, Saucisse, Wilfrid, Mazier, Vincent, Simon, Elke, Binder, Caterina, Catania, Luigi, Bellocchio, Roman A, Romanov, Stéphane, Léon, Isabelle, Matias, Philippe, Zizzari, Carmelo, Quarta, Astrid, Cannich, Kana, Meece, Delphine, Gonzales, Samantha, Clark, Julia M, Becker, Giles S H, Yeo, Xavier, Fioramonti, Florian T, Merkle, Sharon L, Wardlaw, Tibor, Harkany, Federico, Massa, Giovanni, Marsicano, Daniela, Cota |
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| Přispěvatelé: | DESAILLY, Marion, Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Medizinische Universität Wien = Medical University of Vienna, Columbia University College of Physicians and Surgeons, University of Cambridge [UK] (CAM), Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Merkle, Florian [0000-0002-8513-2998], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
endocrine system CB1 receptor Pro-Opiomelanocortin Glutamic Acid CB(1) receptor Mechanistic Target of Rapamycin Complex 1 [SHS]Humanities and Social Sciences GABA Food intake Animals GABAergic Neurons Endocannabinoid Mice Knockout Appetite Regulation digestive oral and skin physiology Neural Inhibition Feeding Behavior POMC neuron Mice Inbred C57BL Phenotype nervous system Melanocortin mTOR [SHS] Humanities and Social Sciences Glutamate hormones hormone substitutes and hormone antagonists Paraventricular Hypothalamic Nucleus Signal Transduction |
| Zdroj: | Cell Reports Cell Reports, Elsevier Inc, 2021, 37 (2), pp.109800. ⟨10.1016/j.celrep.2021.109800⟩ |
| ISSN: | 2211-1247 |
| Popis: | International audience; Hypothalamic pro-opiomelanocortin (POMC) neurons are known to trigger satiety. However, these neuronal cells encompass heterogeneous subpopulations that release γ-aminobutyric acid (GABA), glutamate, or both neurotransmitters, whose functions are poorly defined. Using conditional mutagenesis and chemogenetics, we show that blockade of the energy sensor mechanistic target of rapamycin complex 1 (mTORC1) in POMC neurons causes hyperphagia by mimicking a cellular negative energy state. This is associated with decreased POMC-derived anorexigenic α-melanocyte-stimulating hormone and recruitment of POMC/GABAergic neurotransmission, which is restrained by cannabinoid type 1 receptor signaling. Electrophysiology and optogenetic studies further reveal that pharmacological blockade of mTORC1 simultaneously activates POMC/GABAergic neurons and inhibits POMC/glutamatergic ones, implying that the functional specificity of these subpopulations relies on mTORC1 activity. Finally, POMC neurons with different neurotransmitter profiles possess specific molecular signatures and spatial distribution. Altogether, these findings suggest that mTORC1 orchestrates the activity of distinct POMC neurons subpopulations to regulate feeding behavior. |
| Databáze: | OpenAIRE |
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