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mTORC1 pathway disruption abrogates the effects of the ciliary neurotrophic factor on energy balance and hypothalamic neuroinflammation

dc.rights.licenseopenen_US
dc.relation.isnodouble49801ba8-5981-4502-bdef-111cfe938b0f*
dc.contributor.authorANDRE, Caroline
dc.contributor.authorCATANIA, Caterina
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorREMUS-BOREL, Julie
dc.contributor.authorLADEVEZE, Elodie
dc.contributor.authorLESTE-LASSERRE, Thierry
dc.contributor.authorMAZIER, Wilfrid
dc.contributor.authorBINDER, Elke
dc.contributor.authorGONZALES, Delphine
dc.contributor.authorCLARK, Samantha
dc.contributor.authorGUZMAN-QUEVEDO, Omar
dc.contributor.authorABROUS, Djoher Nora
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorLAYE, Sophie
dc.contributor.authorCOTA, Daniela
dc.date.accessioned2021-09-23T08:38:51Z
dc.date.available2021-09-23T08:38:51Z
dc.date.issued2018-05
dc.identifier.issn0889-1591en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/112345
dc.description.abstractEnCiliary neurotrophic factor (CNTF) potently decreases food intake and body weight in diet-induced obese mice by acting through neuronal circuits and pathways located in the arcuate nucleus (ARC) of the hypothalamus. CNTF also exerts pro-inflammatory actions within the brain. Here we tested whether CNTF modifies energy balance by inducing inflammatory responses in the ARC and whether these effects depend upon the mechanistic target of rapamycin complex 1 (mTORC1) pathway, which regulates both energy metabolism and inflammation. To this purpose, chow- and high fat diet (HFD)- fed mice lacking the S6 kinase 1 (S6K1?/?), a downstream target of mTORC1, and their wild-type (WT) littermates received 12 days continuous intracerebroventricular (icv) infusion of the CNTF analogue axokine (CNTFAx15). Behavioral, metabolic and molecular effects were evaluated. Central chronic administration of CNTFAx15 decreased body weight and feed efficiency in WT mice only, when fed HFD, but not chow. These metabolic effects correlated with increased number of iba-1 positive microglia specifically in the ARC and were accompanied by significant increases of IL-1? and TNF-? mRNA expression in the hypothalamus. Hypothalamic iNOS and SOCS3 mRNA, molecular markers of pro-inflammatory response, were also increased by CNTFAx15. All these changes were absent in S6K1?/? mice. This study reveals that CNTFAx15 requires a functional S6K1 to modulate energy balance and hypothalamic inflammation in a diet-dependent fashion. Further investigations should determine whether S6K1 is a suitable target for the treatment of pathologies characterized by a high neuroinflammatory state.
dc.language.isoENen_US
dc.subject.enCNTF
dc.subject.enGlia cells
dc.subject.enHypothalamus
dc.subject.enInflammation
dc.subject.enMicroglia
dc.subject.enmTOR
dc.subject.enObesity
dc.subject.enS6K1
dc.title.enmTORC1 pathway disruption abrogates the effects of the ciliary neurotrophic factor on energy balance and hypothalamic neuroinflammation
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.bbi.2018.03.014en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed29548998en_US
bordeaux.journalBrain, Behavior, and Immunityen_US
bordeaux.page325-334en_US
bordeaux.volume70en_US
bordeaux.hal.laboratoriesNutriNeurO (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286en_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
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Brain,%20Behavior,%20and%20Immunity&rft.date=2018-05&rft.volume=70&rft.spage=325-334&rft.epage=325-334&rft.eissn=0889-1591&rft.issn=0889-1591&rft.au=ANDRE,%20Caroline&CATANIA,%20Caterina&REMUS-BOREL,%20Julie&LADEVEZE,%20Elodie&LESTE-LASSERRE,%20Thierry&rft.genre=article


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