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dc.contributorCasals i Farré, Núria
dc.contributorUniversitat Internacional de Catalunya. Departament de Ciències Bàsiques
dc.creatorRamírez Flores, Sara
dc.date2014-07-18
dc.date.accessioned2019-01-24T11:45:54Z
dc.date.available2019-01-24T11:45:54Z
dc.identifierB 18913 - 2014
dc.identifierhttp://hdl.handle.net/10803/276184
dc.identifier.urihttp://hdl.handle.net/20.500.12328/703
dc.descriptionRecent data suggest that ghrelin exerts its orexigenic action through regulation of hypothalamic AMP-activated protein kinase pathway, leading to a decline in malonyl-CoA levels and desinhibition of carnitine palmitoyltransferase 1A (CPT1A), which increases mitochondrial fatty acid oxidation and ultimately enhances the expression of the orexigenic neuropeptides agouti-related protein (AgRP) and neuropeptide Y (NPY). However, it is unclear whether the brain-specific isoform CPT1C, which is located in the endoplasmic reticulum of neurons, may play a role in this action. Here, we demonstrate that the orexigenic action of ghrelin is totally blunted in CPT1C knockout (KO) mice, despite having the canonical ghrelin signaling pathway activated. We also demonstrate that ghrelin elicits a marked upregulation of hypothalamic C18:0 ceramide levels mediated by CPT1C. Notably, central inhibition of ceramide synthesis with myriocin negated the orexigenic action of ghrelin and normalized the levels of AgRP and NPY, as well as their key transcription factors phosphorylated cAMP-response element-binding protein and forkhead box O1. Furthermore, central treatment with ceramide induced food intake and orexigenic neuropeptides expression in CPT1C KO mice. Third, we demonstrate that ceramides act increasing the BSX expression, the transcription factor that works coordinately with pCREB and FoxO1 to increase orexigenic neuropeptides. Finally we link CPT1C and longevity as we have seen that CPT1CKO mice have reduced lifespan. Overall, these data indicate that, in addition to formerly reported mechanisms, ghrelin also induces food intake through regulation of hypothalamic CPT1C and ceramide metabolism
dc.formatapplication/pdf
dc.format175 p.
dc.languageeng
dc.publisherUniversitat Internacional de Catalunya
dc.rightsL'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourceTDX (Tesis Doctorals en Xarxa)
dc.subjectCarnitina palmitoiltransferas 1c
dc.subjectCarnitine
dc.subjectPalmitoyltransferase 1C
dc.subjectGhrelina
dc.subjectGhrelin
dc.subjectCeramides
dc.subjectCeramide
dc.subjectBSX
dc.subjectNPY
dc.subjectAgRP
dc.subjectNeuro
dc.subject576
dc.subject577
dc.titleHypothalamic Ceramide levels regulated by CPT1C mediate the orexigenic effect of Ghrelin
dc.typeinfo:eu-repo/semantics/doctoralThesis
dc.typeinfo:eu-repo/semantics/publishedVersion


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