Melanin-concentrating hormone acts through hypothalamic kappa opioid system and p70S6K to stimulate acute food intake

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Romero-Picó, Amparoca
• dc.contributor.author Sanchez-Rebordelo, Estrellaca
• dc.contributor.author Imbernon, Monicaca
• dc.contributor.author Gónzalez-Touceda, Davidca
• dc.contributor.author Folgueira, Cintiaca
• dc.contributor.author Senra, Anaca
• dc.contributor.author Fernø, Johanca
• dc.contributor.author Blouet, Clémenceca
• dc.contributor.author Cabrera Ortega, Robertoca
• dc.contributor.author Gestel, Margriet vanca
• dc.contributor.author Adan, Roger A.ca
• dc.contributor.author López, Miguelca
• dc.contributor.author Maldonado, Rafael, 1961-ca
• dc.contributor.author Nogueiras, Rubenca
• dc.contributor.author Diéguez, Carlosca
• dc.date.accessioned 2018-04-06T08:07:38Z
• dc.date.issued 2018
• dc.description.abstract Melanin-Concentrating Hormone (MCH) is one of the most relevant orexigenic factors specifically located in the lateral hypothalamic area (LHA), with its physiological relevance demonstrated in studies using several genetically manipulated mice models. However, the central mechanisms controlling MCH-induced hyperphagia remain largely uncharacterized. Here, we show that central injection of MCH in mice deficient for kappa opoid receptor (k-OR) failed to stimulate feeding. To determine the hypothalamic area responsible for this MCH/k-OR interaction, we performed virogenetic studies and found that downregulation of k-OR by adeno-associated viruses (shOprk1-AAV) in LHA, but not in other hypothalamic nuclei, was sufficient to block MCH-induced food intake. Next, we sought to investigate the molecular signaling pathway within the LHA that mediates acute central MCH stimulation of food intake. We found that MCH activates k-OR and that increased levels of phosphorylated extracellular signal regulated kinase (ERK) are associated with downregulation of phospho-S6 Ribosomal Protein. This effect was prevented when a pharmacological inhibitor of k-OR was co-administered with MCH. Finally, the specific activation of the direct upstream regulator of S6 (p70S6K) in the LHA attenuated MCH-stimulated food consumption. Our results reveal that lateral hypothalamic k-OR system modulates the orexigenic action of MCH via the p70S6K/S6 pathway.
• dc.description.sponsorship This work has been supported by grants from Ministerio de Economia y Competitividad (CD: BFU2014-55871; RN: BFU2015-70664-R; ML: SAF2015-71026-R), Xunta de Galicia (ML: 2015- CP079; RN: 2015-CP080 and PIE13/00024); Fundacion SEEN (RN); Helse Vest RHF (JF); Fundación AstraZeneca (RN: 2016-PO031); Centro de Investigacion Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutricion (CIBERobn). CIBERobn is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds. The research leading to these results has also received funding from the European Community's Seventh Framework Programme under the following grant: RN: ERC StG281408
• dc.format.mimetype application/pdf
• dc.identifier.citation Romero-Picó A, Sanchez-Rebordelo E, Imbernon M, González-Touceda D, Folgueira C, Senra A et al. Melanin-Concentrating Hormone acts through hypothalamic kappa opioid system and p70S6K to stimulate acute food intake. Neuropharmacology. 2018 Mar 1;130:62-70. DOI: 10.1016/j.neuropharm.2017.11.040
• dc.identifier.doi http://dx.doi.org/10.1016/j.neuropharm.2017.11.040
• dc.identifier.issn 0028-3908
• dc.identifier.uri http://hdl.handle.net/10230/34302
• dc.language.iso eng
• dc.publisher Elsevierca
• dc.relation.ispartof Neuropharmacology. 2018 Mar 1;130:62-70
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/281408
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-55871
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-70664-R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-71026-R
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.neuropharm.2017.11.040
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.other Hipotàlem
• dc.subject.other Hormones hipotalàmiques
• dc.subject.other Opiacis -- Receptors
• dc.subject.other Aliments -- Consum
• dc.title Melanin-concentrating hormone acts through hypothalamic kappa opioid system and p70S6K to stimulate acute food intakeca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion