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Central anorexigenic actions of bile acids are mediated by TGR5

dc.rights.licenseopenen_US
dc.contributor.authorPERINO, Alessia
dc.contributor.authorVELAZQUEZ-VILLEGAS, Laura A.
dc.contributor.authorBRESCIANI, Nadia
dc.contributor.authorSUN, Yu
dc.contributor.authorHUANG, Qingyao
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorFENELON, Valerie S.
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorCASTELLANOS-JANKIEWICZ, Ashley
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorZIZZARI, Philippe
dc.contributor.authorBRUSCHETTA, Giuseppe
dc.contributor.authorJIN, Sungho
dc.contributor.authorBALEISYTE, Aiste
dc.contributor.authorGIOIELLO, Antimo
dc.contributor.authorPELLICCIARI, Roberto
dc.contributor.authorIVANISEVIC, Julijana
dc.contributor.authorSCHNEIDER, Bernard L.
dc.contributor.authorDIANO, Sabrina
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorCOTA, Daniela
dc.contributor.authorSCHOONJANS, Kristina
dc.date.accessioned2022-03-02T12:50:42Z
dc.date.available2022-03-02T12:50:42Z
dc.date.issued2021-05-01
dc.identifier.issn2522-5812en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/128793
dc.description.abstractEnBile acids (BAs) are signalling molecules that mediate various cellular responses in both physiological and pathological processes. Several studies report that BAs can be detected in the brain1, yet their physiological role in the central nervous system is still largely unknown. Here we show that postprandial BAs can reach the brain and activate a negative-feedback loop controlling satiety in response to physiological feeding via TGR5, a G-protein-coupled receptor activated by multiple conjugated and unconjugated BAs2 and an established regulator of peripheral metabolism3,4,5,6,7,8. Notably, peripheral or central administration of a BA mix or a TGR5-specific BA mimetic (INT-777) exerted an anorexigenic effect in wild-type mice, while whole-body, neuron-specific or agouti-related peptide neuronal TGR5 deletion caused a significant increase in food intake. Accordingly, orexigenic peptide expression and secretion were reduced after short-term TGR5 activation. In vitro studies demonstrated that activation of the Rho–ROCK–actin-remodelling pathway decreases orexigenic agouti-related peptide/neuropeptide Y (AgRP/NPY) release in a TGR5-dependent manner. Taken together, these data identify a signalling cascade by which BAs exert acute effects at the transition between fasting and feeding and prime the switch towards satiety, unveiling a previously unrecognized role of physiological feedback mediated by BAs in the central nervous system.
dc.description.sponsorshipDéveloppment d'une infrastructure française distribuée coordonnéeen_US
dc.description.sponsorshipLa signalisation des acides biliaires dans le cerveau et son rôle dans le contrôle métabolique - ANR-17-CE14-0007en_US
dc.description.sponsorshipInnovations instrumentales et procédurales en psychopathologie expérimentale chez le rongeur - ANR-10-EQPX-0008en_US
dc.language.isoENen_US
dc.rights*
dc.rights.uri*
dc.title.enCentral anorexigenic actions of bile acids are mediated by TGR5
dc.title.alternativeNat Metab.en_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s42255-021-00398-4en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed34031591en_US
bordeaux.journalNature Metabolismen_US
bordeaux.page595-603en_US
bordeaux.volume3en_US
bordeaux.hal.laboratoriesNeurocentre Magendie - UMR-S 1215en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDÉcole Polytechnique Fédérale de Lausanneen_US
bordeaux.identifier.funderIDAXA Research Funden_US
hal.identifierhal-03594102
hal.version1
hal.date.transferred2022-03-02T12:50:46Z
hal.exporttrue
dc.rights.ccen_US
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