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dc.contributor.authorDi Pietro, Natalia
dc.contributor.authorMarcovecchio, M Loredana
dc.contributor.authorDi Silvestre, Sara
dc.contributor.authorde Giorgis, Tommaso
dc.contributor.authorCordone, Vincenzo Giuseppe Pio
dc.contributor.authorLanuti, Paola
dc.contributor.authorChiarelli, Francesco
dc.contributor.authorBologna, Giuseppina
dc.contributor.authorMohn, Angelika
dc.contributor.authorPandolfi, Assunta
dc.date.accessioned2018-08-01T14:16:24Z
dc.date.available2018-08-01T14:16:24Z
dc.date.issued2017-03-05
dc.identifier.issn0303-7207
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/278604
dc.description.abstractChildhood obesity is commonly associated with early signs of endothelial dysfunction, characterized by impairment of insulin signaling and vascular Nitric Oxide (NO) availability. However, the underlying mechanisms remain to be established. Hence, we tested the hypothesis that endothelial insulin-stimulated NO production and availability was impaired and related to Endoplasmic Reticulum (ER) in human umbilical vein endothelial cells (HUVECs) cultured with plasma obtained from pre-pubertal obese (OB) children. OB children (N = 28, age: 8.8 ± 2.2; BMI z-score: 2.15 ± 0.39) showed impaired fasting glucose, insulin and HOMA-IR than normal weight children (CTRL; N = 28, age: 8.8 ± 1.7; BMI z-score: 0.17 ± 0.96). The in vitro experiments showed that OB-plasma significantly impaired endothelial insulin-stimulated NO production and bioavailability compared to CTRL-plasma. In parallel, in HUVECs OB-plasma increased GRP78 and activated PERK, eIF2α, IkBα and ATF6 (all ER stress markers). Moreover, OB-plasma increased NF-κB activation and its nuclear translocation. Notably, all these effects proved to be significantly restored by using PBA and TUDCA, known ER stress inhibitors. Our study demonstrate for the first time that plasma from obese children is able to induce in vitro endothelial insulin resistance, which is characterized by reduced insulin-stimulated NO production and bioavailability, endothelial ER stress and increased NF-κB activation.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectCell Nucleus
dc.subjectHumans
dc.subjectObesity
dc.subjectNitric Oxide
dc.subjectInsulin
dc.subjectNF-kappa B
dc.subjectCyclic GMP
dc.subjectProtein Transport
dc.subjectBiological Availability
dc.subjectPhosphorylation
dc.subjectPuberty
dc.subjectModels, Biological
dc.subjectChild
dc.subjectProto-Oncogene Proteins c-akt
dc.subjectActivating Transcription Factor 6
dc.subjectNitric Oxide Synthase Type III
dc.subjectHuman Umbilical Vein Endothelial Cells
dc.subjectEndoplasmic Reticulum Stress
dc.subjectBiomarkers
dc.titlePlasma from pre-pubertal obese children impairs insulin stimulated Nitric Oxide (NO) bioavailability in endothelial cells: Role of ER stress.
dc.typeArticle
prism.endingPage62
prism.publicationDate2017
prism.publicationNameMol Cell Endocrinol
prism.startingPage52
prism.volume443
dc.identifier.doi10.17863/CAM.25944
dcterms.dateAccepted2017-01-02
rioxxterms.versionofrecord10.1016/j.mce.2017.01.001
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-03
dc.contributor.orcidMarcovecchio, Loredana [0000-0002-4415-316X]
dc.identifier.eissn1872-8057
rioxxterms.typeJournal Article/Review
cam.issuedOnline2017-01-03


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International