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dc.contributor.authorPellegrinelli, Vanessaen
dc.contributor.authorPeirce, Vivian Jen
dc.contributor.authorHoward, Lauraen
dc.contributor.authorVirtue, Samuelen
dc.contributor.authorTürei, Dénesen
dc.contributor.authorSenzacqua, Martinaen
dc.contributor.authorFrontini, Andreaen
dc.contributor.authorDalley, Jeffreyen
dc.contributor.authorHorton, Antony Ren
dc.contributor.authorBidault, Guillaumeen
dc.contributor.authorSeveri, Ileniaen
dc.contributor.authorWhittle, Andrewen
dc.contributor.authorRahmouni, Kamalen
dc.contributor.authorSaez-Rodriguez, Julioen
dc.contributor.authorCinti, Saverioen
dc.contributor.authorDavies, Alun Men
dc.contributor.authorVidal-Puig, Antonioen
dc.date.accessioned2018-12-20T00:30:17Z
dc.date.available2018-12-20T00:30:17Z
dc.date.issued2018-11-26en
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287204
dc.description.abstractActivation of brown adipose tissue-mediated thermogenesis is a strategy for tackling obesity and promoting metabolic health. BMP8b is secreted by brown/beige adipocytes and enhances energy dissipation. Here we show that adipocyte-secreted BMP8b contributes to adrenergic-induced remodeling of the neuro-vascular network in adipose tissue (AT). Overexpression of bmp8b in AT enhances browning of the subcutaneous depot and maximal thermogenic capacity. Moreover, BMP8b-induced browning, increased sympathetic innervation and vascularization of AT were maintained at 28°C, a condition of low adrenergic output. This reinforces the local trophic effect of BMP8b. Innervation and vascular remodeling effects required BMP8b signaling through the adipocytes to 1) secrete neuregulin-4 (NRG4), which promotes sympathetic axon growth and branching in vitro, and 2) induce a pro-angiogenic transcriptional and secretory profile that promotes vascular sprouting. Thus, BMP8b and NRG4 can be considered as interconnected regulators of neuro-vascular remodeling in AT and are potential therapeutic targets in obesity.
dc.description.sponsorshipthe American Heart Association (14EIA18860041) and the University of Iowa Fraternal Order of Eagles Diabetes Research Center.
dc.format.mediumElectronicen
dc.languageengen
dc.publisherSpringer Nature
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject3T3-L1 Cellsen
dc.subjectAnimalsen
dc.subjectMice, Inbred C57BLen
dc.subjectMice, Transgenicen
dc.subjectMiceen
dc.subjectVascular Endothelial Growth Factor Aen
dc.subjectNeuregulinsen
dc.subjectBone Morphogenetic Proteinsen
dc.subjectAdrenergic Agentsen
dc.subjectProteomicsen
dc.subjectSignal Transductionen
dc.subjectThermogenesisen
dc.subjectNeovascularization, Physiologicen
dc.subjectModels, Biologicalen
dc.subjectFemaleen
dc.subjectSubcutaneous Faten
dc.subjectAdipose Tissue, Brownen
dc.subjectAdipocytes, Brownen
dc.titleAdipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue.en
dc.typeArticle
prism.issueIdentifier1en
prism.publicationDate2018en
prism.publicationNameNature communicationsen
prism.startingPage4974
prism.volume9en
dc.identifier.doi10.17863/CAM.34512
dcterms.dateAccepted2018-10-22en
rioxxterms.versionofrecord10.1038/s41467-018-07453-xen
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-11-26en
dc.contributor.orcidFrontini, Andrea [0000-0002-7381-4107]
dc.contributor.orcidDalley, Jeffrey [0000-0002-2282-3660]
dc.contributor.orcidBidault, Guillaume [0000-0002-8396-9962]
dc.contributor.orcidSeveri, Ilenia [0000-0002-3985-1131]
dc.contributor.orcidRahmouni, Kamal [0000-0001-5136-6748]
dc.contributor.orcidSaez-Rodriguez, Julio [0000-0002-8552-8976]
dc.contributor.orcidCinti, Saverio [0000-0003-0362-5017]
dc.contributor.orcidVidal-Puig, Antonio [0000-0003-4220-9577]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBritish Heart Foundation (RG/12/13/29853)
pubs.funder-project-idMRC (MC_UU_12012/2)
pubs.funder-project-idWellcome Trust (100574/Z/12/Z)
pubs.funder-project-idBBSRC (BB/J009865/1)
pubs.funder-project-idMRC (G0400192)
pubs.funder-project-idMRC (MC_UU_12012/5)
pubs.funder-project-idBritish Heart Foundation (PG/12/53/29714)
pubs.funder-project-idMRC (G0600717B)
pubs.funder-project-idMRC (G0802051)
pubs.funder-project-idMRC (MC_G0802535)
pubs.funder-project-idMRC (MC_UU_00014/2)
pubs.funder-project-idMRC (MC_UU_00014/5)
pubs.funder-project-idBritish Heart Foundation (RG/18/7/33636)


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