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dc.contributor.authorVázquez Pérez, Patriciaes_ES
dc.contributor.authorHernández-Sánchez, Catalinaes_ES
dc.contributor.authorEscalona-Garrido, Carmenes_ES
dc.contributor.authorPereira, Lauraes_ES
dc.contributor.authorContreras, Cristinaes_ES
dc.contributor.authorLópez, Migueles_ES
dc.contributor.authorBalsinde, Jesúses_ES
dc.contributor.authorPablo, Flora dees_ES
dc.contributor.authorValverde, Ángela M.es_ES
dc.date.accessioned2018-10-29T12:42:06Z-
dc.date.available2018-10-29T12:42:06Z-
dc.date.issued2018-10-23-
dc.identifier.citationJournal of Lipid Research 59(12): 2308-2320 (2018)es_ES
dc.identifier.issn0022-2275-
dc.identifier.urihttp://hdl.handle.net/10261/171702-
dc.description.abstractTyrosine hydroxylase (TH) catalyzes the first step in catecholamines synthesis. We studied the impact of reduced TH in brown adipose tissue (BAT) activation. In adult heterozygous (Th+/-) mice, dopamine and noradrenaline (NA) content in BAT decreased after cold exposure. This reduced catecholaminergic response did not impair cold adaptation, since these mice induced uncoupling protein-1 (UCP1) and maintained BAT temperature to a similar extent than controls (Th+/+). Possible compensatory mechanisms implicated were studied. Prdm16 and Fgf21 expression, key genes in BAT activation, were elevated in Th+/- mice at thermoneutrality from day 18.5 of embryonic life. Likewise, plasma FGF21 and liver Fgf21 mRNA were increased. Analysis of endoplasmic reticulum (ER) stress, a process that triggers elevations in FGF21, showed higher phospho-IRE1, phospho-JNK and CHOP in BAT of Th+/- mice at thermoneutrality. Also, increased lipolysis in BAT of coldexposure Th+/- mice was demonstrated by increased phosphorylation of hormone-sensitive lipase (HSL), as well as diacylglycerol (DAG) and free fatty acids (FFA) content. Overall, these results indicate that the mild effects of Th haploinsufficiency on BAT function are likely due to compensatory mechanisms involving elevations in Fgf21 and Prdm16 and through adaptive changes in the lipid profile.es_ES
dc.description.sponsorshipThis work was supported by a Ministry of Science, Technology and Innovation grants BFU 2010-15868 to FdeP and CHS, SAF2015-73000-EXP and SAF2016-80883 to JB and SAF2015-65267-R to AMV. We also acknowledge grant INFLAMES (ISCIII PIE14/00045, co-funded by ERDF, “Investing in your future”) to AMV and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas CIBERdem This is an initiative of the Instituto de Salud Carlos III (Madrid,Spain). We thank MICINN-CSIC and Fondo Social Europeo (FSE) for the JAE-DOC contract (2013 to PV) and CIBERdem contract (to PV 2016).es_ES
dc.language.isoenges_ES
dc.publisherAmerican Society for Biochemistry and Molecular Biologyes_ES
dc.relationMINECO/ICTI2013-2016/SAF2015-73000-EXPes_ES
dc.relationMINECO/ICTI2013-2016/SAF2016-80883-Res_ES
dc.relationMINECO/ICTI2013-2016/SAF2015-65267-Res_ES
dc.relationMINECO/ICTI2013-2016/SAF2015-73000-EXP-
dc.relation.isversionofPublisher's versiones_ES
dc.rightsopenAccesses_ES
dc.subjectAdipose tissuees_ES
dc.subjectBrown adipose tissuees_ES
dc.subjectCatecholamineses_ES
dc.subjectDiabeteses_ES
dc.subjectFatty acidses_ES
dc.subjectFGF21es_ES
dc.subjectMetabolic diseasees_ES
dc.subjectObesityes_ES
dc.subjectPRDM16es_ES
dc.subjectUCP-1es_ES
dc.titleIncreased FGF21 in brown adipose tissue of tyrosine hydroxylase heterozygous mice: implications for cold adaptationes_ES
dc.title.alternativeIncreased FGF21 expression in BAT of TH heterozygous micees_ES
dc.typeartículoes_ES
dc.identifier.doi10.1194/jlr.M085209-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.1194/jlr.M085209es_ES
dc.identifier.e-issn1539-7262-
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.contributor.funderInstituto de Salud Carlos IIIes_ES
dc.contributor.funderEuropean Commissiones_ES
dc.relation.csices_ES
oprm.item.hasRevisionno ko 0 false*
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004837es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000780es_ES
dc.contributor.orcidHernández-Sánchez, Catalina [0000-0002-0846-5019]es_ES
dc.contributor.orcidContreras, Cristina [0000-0002-7015-7922]es_ES
dc.contributor.orcidBalsinde, Jesús [0000-0002-4157-6714]es_ES
dc.contributor.orcidPablo, Flora de [0000-0002-8357-5074 ]es_ES
dc.contributor.orcidValverde, Ángela M. [0000-0003-1192-9045]es_ES
dc.identifier.pmid30352954-
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