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CRH-R2 signalling modulates feeding and circadian gene expression in hypothalamic mHypoA-2/30 neurons

dc.creatorAlcántara-Alonso, Viridianaes_ES
dc.creatorDallmann, Robertes_ES
dc.creatorLehnert, Hendrikes_ES
dc.creatorGortari, Patricia dees_ES
dc.creatorGrammatopoulos, Dimitris K.es_ES
dc.date2023
dc.date.accessioned2025-03-10T17:43:28Z
dc.date.available2025-03-10T17:43:28Z
dc.date.issued2023
dc.identifierJC07NC23es_ES
dc.identifier.urihttp://repositorio.inprf.gob.mx/handle/123456789/8233
dc.identifier.urihttps://doi.org/10.3389/fendo.2023.1266081
dc.descriptionThe hypothalamic type 2 corticotropin releasing hormone receptor (CRH-R2) plays critical roles in homeostatic regulation, particularly in fine tuning stress recovery. During acute stress, the CRH-R2 ligands CRH and urocortins promote adaptive responses and feeding inhibition. However, in rodent models of chronic stress, over-exposure of hypothalamic CRH-R2 to its cognate agonists is associated with urocortin 2 (Ucn2) resistance; attenuated cAMP-response element binding protein (CREB) phosphorylation and increased food intake. The molecular mechanisms involved in these altered CRH-R2 signalling responses are not well described. In the present study, we used the adult mouse hypothalamus-derived cell line mHypoA-2/30 to investigate CRH-R2 signalling characteristics focusing on gene expression of molecules involved in feeding and circadian regulation given the role of clock genes in metabolic control. We identified functional CRH-R2 receptors expressed in mHypoA-2/30 cells that differentially regulate CREB and AMP-activated protein kinase (AMPK) phosphorylation and downstream expression of the appetite-regulatory genes proopiomelanocortin (Pomc) and neuropeptide Y (Npy) in accordance with an anorexigenic effect. We studied for the first time the effects of Ucn2 on clock genes in native and in a circadian bioluminescence reporter expressing mHypoA-2/30 cells, detecting enhancing effects of Ucn2 on mRNA levels and rhythm amplitude of the circadian regulator Aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1), which could facilitate anorexic responses in the activity circadian phase. These data uncover novel aspects of CRH-R2 hypothalamic signalling that might be important in regulation of circadian feeding during stress responses.es_ES
dc.formatPDFes_ES
dc.language.isoenges_ES
dc.publisherFrontiers Research Foundationes_ES
dc.relation14:1266081
dc.rightsAcceso Cerradoes_ES
dc.titleCRH-R2 signalling modulates feeding and circadian gene expression in hypothalamic mHypoA-2/30 neuronses_ES
dc.typeArtículoes_ES
dc.contributor.affiliationTranslational Medicine, Warwick Medical School, University of Warwick, Coventry, United Kingdom
dc.contributor.emailD.Grammatopoulos@warwick.ac.uk (Dimitris K. Grammatopoulos) ; gortari@imp.edu.mx (Patricia de Gortari)
dc.relation.jnabreviadoFRONT ENDOCRINOL
dc.relation.journalFrontiers in Endocrinology
dc.identifier.placeSuiza
dc.date.published2023
dc.identifier.organizacionInstituto Nacional de Psiquiatría Ramón de la Fuente Muñiz
dc.identifier.eissn1664-2392
dc.identifier.doi10.3389/fendo.2023.1266081
dc.subject.kwFeeding
dc.subject.kwHypothalamic peptides
dc.subject.kwCRH-R2
dc.subject.kwUrocortin 2 (UCN2)
dc.subject.kwAMPK
dc.subject.kwCREB
dc.subject.kwCircadian rhythm


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