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dc.contributor.authorContreras, Cristina
dc.contributor.authorGonzález-García, Ismael
dc.contributor.authorMartínez-Sánchez, Noelia
dc.contributor.authorSeoane-Collazo, Patricia
dc.contributor.authorJacas i Mateu, Jordi
dc.contributor.authorMorgan, Donald A.
dc.contributor.authorSerra, Dolors
dc.contributor.authorGallego, Rosalía
dc.contributor.authorGonzalez, Francisco
dc.contributor.authorCasals i Farré, Núria
dc.contributor.authorNogueiras, Rubén
dc.contributor.authorRahmouni, Kamal
dc.contributor.authorDiéguez, Carlos
dc.contributor.authorLópez, Miguel
dc.date.accessioned2019-12-22T17:44:37Z
dc.date.available2019-12-22T17:44:37Z
dc.date.issued2014-10
dc.identifier.citationContreras, Cristina; González-García, Ismael; Martínez-Sánchez, Noelia [et al.]. Central ceramide-induced hypothalamic lipotoxicity and ER stress regulate energy balance. Cell Press, 2014, vol. 9, núm. 1, p. 366-377. Disponible en: <https://www.sciencedirect.com/science/article/pii/S2211124714007335?via%3Dihub>. Fecha de acceso: 22 dic. 2019. DOI: 10.1016/j.celrep.2014.08.057ca
dc.identifier.issn2211-1247ca
dc.identifier.urihttp://hdl.handle.net/20.500.12328/1404
dc.description.abstractHypothalamic endoplasmic reticulum (ER) stress is a key mechanism leading to obesity. Here, we demonstrate that ceramides induce lipotoxicity and hypothalamic ER stress, leading to sympathetic inhibition, reduced brown adipose tissue (BAT) thermogenesis, and weight gain. Genetic overexpression of the chaperone GRP78/BiP (glucose-regulated protein 78 kDa/binding immunoglobulin protein) in the ventromedial nucleus of the hypothalamus (VMH) abolishes ceramide action by reducing hypothalamic ER stress and increasing BAT thermogenesis, which leads to weight loss and improved glucose homeostasis. The pathophysiological relevance of this mechanism is demonstrated in obese Zucker rats, which show increased hypothalamic ceramide levels and ER stress. Overexpression of GRP78 in the VMH of these animals reduced body weight by increasing BAT thermogenesis as well as decreasing leptin and insulin resistance and hepatic steatosis. Overall, these data identify a triangulated signaling network involving central ceramides, hypothalamic lipotoxicity/ER stress, and BAT thermogenesis as a pathophysiological mechanism of obesity.ca
dc.format.extent13ca
dc.language.isoengca
dc.publisherElsevierca
dc.relation.ispartofCell Reportsca
dc.relation.ispartofseries9;1
dc.rightsThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).ca
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.otherHipotàlemca
dc.subject.otherObesitat
dc.subject.otherLípids
dc.subject.otherHipotálamo
dc.subject.otherObesidad
dc.subject.otherLípidos
dc.subject.otherHypothalamus
dc.subject.otherObesity
dc.subject.otherLipids
dc.titleCentral ceramide-induced hypothalamic lipotoxicity and ER stress regulate energy balanceca
dc.typeinfo:eu-repo/semantics/articleca
dc.description.versioninfo:eu-repo/semantics/acceptedVersionca
dc.embargo.termscapca
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/281854ca
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/245009ca
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/3PN/BFU-2010-14968ca
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/3PN/SAF2011-30520-C02-01ca
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/1PE/BFU2012-35255ca
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/3PN/SAF2011-30520-C02-02ca
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/3PN/BFU2011-29102ca
dc.subject.udc61ca
dc.identifier.doihttps://dx.doi.org/10.1016/j.celrep.2014.08.057ca


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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-nd/3.0/
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