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dc.contributor.authorLopez-Guadamillas, Elena
dc.contributor.authorFernandez-Marcos, Pablo J
dc.contributor.authorPantoja, Cristina 
dc.contributor.authorMuñoz-Martin, Maribel
dc.contributor.authorMartinez Garcia, Maria Dolores 
dc.contributor.authorGómez-López, Gonzalo 
dc.contributor.authorCampos Olivas, Ramon 
dc.contributor.authorValverde, Angela M
dc.contributor.authorSerrano Marugan, Manuel 
dc.date.accessioned2019-12-23T10:03:14Z
dc.date.available2019-12-23T10:03:14Z
dc.date.issued2016-10
dc.identifier.citationSci Rep. 2016 ;6:32512.es_ES
dc.identifier.issn2045-2322es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/8868
dc.descriptionWe are grateful to Orlando Dominguez for excellent technical assistance. We also thank Gema Iglesias for animal handling. E.L.-G. was recipient of a predoctoral contract from the Spanish Ministry of Education. P.J.F.-M. has been funded by the Spanish Association Against Cancer (aecc). Work in the laboratory of M.S. is funded by the CNIO and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (SAF project), the European Research Council (ERC Advanced Grant), the Regional Government of Madrid co-funded by the European Social Fund (ReCaRe project), the Botin Foundation and Banco Santander (Santander Universities Global Division), the Ramon Areces Foundation, and the AXA Foundation.es_ES
dc.description.abstractFasting is a physiological stress that elicits well-known metabolic adaptations, however, little is known about the role of stress-responsive tumor suppressors in fasting. Here, we have examined the expression of several tumor suppressors upon fasting in mice. Interestingly, p21 mRNA is uniquely induced in all the tissues tested, particularly in liver and muscle (>10 fold), and this upregulation is independent of p53. Remarkably, in contrast to wild-type mice, p21-null mice become severely morbid after prolonged fasting. The defective adaptation to fasting of p21-null mice is associated to elevated energy expenditure, accelerated depletion of fat stores, and premature activation of protein catabolism in the muscle. Analysis of the liver transcriptome and cell-based assays revealed that the absence of p21 partially impairs the transcriptional program of PPARα, a key regulator of fasting metabolism. Finally, treatment of p21-null mice with a PPARα agonist substantially protects them from their accelerated loss of fat upon fasting. We conclude that p21 plays a relevant role in fasting adaptation through the positive regulation of PPARα.es_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Group es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimals es_ES
dc.subject.meshCyclin-Dependent Kinase Inhibitor p21 es_ES
dc.subject.meshFasting es_ES
dc.subject.meshMale es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Mutant Strains es_ES
dc.subject.meshPPAR alpha es_ES
dc.subject.meshTumor Suppressor Protein p53 es_ES
dc.subject.meshAdaptation, Physiological es_ES
dc.titlep21Cip1 plays a critical role in the physiological adaptation to fasting through activation of PPARαes_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID27721423es_ES
dc.format.volume6es_ES
dc.format.number1es_ES
dc.format.page34542es_ES
dc.identifier.doi10.1038/srep34542es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España) 
dc.contributor.funderAsociación Española Contra el Cáncer 
dc.contributor.funderUnión Europea. Comisión Europea. European Research Council (ERC) 
dc.contributor.funderComunidad de Madrid (España) 
dc.contributor.funderBotín Foundation 
dc.contributor.funderBanco Santander 
dc.contributor.funderFundación Ramón Areces 
dc.contributor.funderFundación AXA 
dc.identifier.e-issn2045-2322es_ES
dc.relation.publisherversionhttps://doi.org/10.1038/srep34542es_ES
dc.identifier.journalScientific reportses_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Antiguos CNIOes_ES
dc.rights.accessRightsopen accesses_ES


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