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The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system

dc.rights.licenseopenen_US
dc.contributor.authorBOUYAKDAN, Khalil
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorMARTIN, Hugo
dc.contributor.authorLIENARD, Fabienne
dc.contributor.authorBUDRY, Lionel
dc.contributor.authorTAIB, Bouchra
dc.contributor.authorRODAROS, Demetra
dc.contributor.authorCHRETIEN, Chloe
dc.contributor.authorBIRON, Eric
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorHUSSON, Zoe
dc.contributor.authorCOTA, Daniela
dc.contributor.authorPENICAUD, Luc
dc.contributor.authorFULTON, Stephanie
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorFIORAMONTI, Xavier
dc.contributor.authorALQUIER, Thierry
dc.date.accessioned2021-09-22T13:10:56Z
dc.date.available2021-09-22T13:10:56Z
dc.date.issued2019-04
dc.identifier.issn0021-9738en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/112328
dc.description.abstractEnGlial cells have emerged as key players in the central control of energy balance and etiology of obesity. Astrocytes play a central role in neural communication via the release of gliotransmitters. Acyl-CoA binding protein (ACBP)-derived endozepines are secreted peptides that modulate the GABAA receptor. In the hypothalamus, ACBP is enriched in arcuate nucleus (ARC) astrocytes, ependymocytes and tanycytes. Central administration of the endozepine octadecaneuropeptide (ODN) reduces feeding and improves glucose tolerance, yet the contribution of endogenous ACBP in energy homeostasis is unknown. We demonstrated that ACBP deletion in GFAP+ astrocytes, but not in Nkx2.1-lineage neural cells, promoted diet-induced hyperphagia and obesity in both male and female mice, an effect prevented by viral rescue of ACBP in ARC astrocytes. ACBP-astrocytes were observed in apposition with proopiomelanocortin (POMC) neurons and ODN selectively activated POMC neurons through the ODN-GPCR but not GABAA, and supressed feeding while increasing carbohydrate utilization via the melanocortin system. Similarly, ACBP overexpression in ARC astrocytes reduced feeding and weight gain. Finally, the ODN-GPCR agonist decreased feeding and promoted weight loss in ob/ob mice. These findings uncover ACBP as an ARC gliopeptide playing a key role in energy balance control and exerting strong anorectic effects via the central melanocortin system.
dc.description.sponsorshipDissection des mécanismes hypothalamiques impliqués dans la détection du statut nutritionnel et régulation de la prise alimentaire via les interactions entre mTORC1, les mélanocortines et les endocannabinoïdes.en_US
dc.description.sponsorshipRôle du récepteur aux cannabinoïdes de type 1 mitochondriale dans les circuits hypothalamiques et son interaction avec la voie mTORC1 dans l'obésité.en_US
dc.language.isoENen_US
dc.subject.enMetabolism
dc.subject.enNeuroscience
dc.title.enThe gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system
dc.typeArticle de revueen_US
dc.identifier.doi10.1172/JCI123454en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed30938715en_US
bordeaux.journalJournal of Clinical Investigationen_US
bordeaux.page2417-2430en_US
bordeaux.volume129en_US
bordeaux.hal.laboratoriesNutriNeurO (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286en_US
bordeaux.issue6en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINRAEen_US
bordeaux.institutionINSERM
bordeaux.teamPsychoneuroimmunologie et Nutrition: Approches expérimentales et cliniquesen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDCanadian Institutes of Health Researchen_US
bordeaux.identifier.funderIDSociété Francophone du Diabèteen_US
bordeaux.identifier.funderIDDiabète Québecen_US
bordeaux.identifier.funderIDFonds de Recherche du Québec - Santéen_US
bordeaux.identifier.funderIDInstitut National de la Santé et de la Recherche Médicaleen_US
bordeaux.identifier.funderIDAgence Nationale de la Rechercheen_US
bordeaux.identifier.funderIDLabEx BRAINen_US
bordeaux.identifier.funderIDDepartement Alimentation Humaine, Institut National de la Recherche Agronomiqueen_US
bordeaux.identifier.funderIDConseil Régional Aquitaineen_US
bordeaux.identifier.funderIDConseil régional de Bourgogne-Franche-Comtéen_US
bordeaux.identifier.funderIDDiabetes Canadaen_US
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
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