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dc.contributor.authorPellegrinelli, Vanessa
dc.contributor.authorPeirce, Vivian J
dc.contributor.authorHoward, Laura
dc.contributor.authorVirtue, Samuel
dc.contributor.authorTürei, Dénes
dc.contributor.authorSenzacqua, Martina
dc.contributor.authorFrontini, Andrea
dc.contributor.authorDalley, Jeffrey
dc.contributor.authorHorton, Antony R
dc.contributor.authorBidault, Guillaume
dc.contributor.authorSeveri, Ilenia
dc.contributor.authorWhittle, Andrew
dc.contributor.authorRahmouni, Kamal
dc.contributor.authorSaez-Rodriguez, Julio
dc.contributor.authorCinti, Saverio
dc.contributor.authorDavies, Alun M
dc.contributor.authorVidal-Puig, Antonio
dc.date.accessioned2018-12-20T00:30:17Z
dc.date.available2018-12-20T00:30:17Z
dc.date.issued2018-11-26
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.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject3T3-L1 Cells
dc.subjectAnimals
dc.subjectMice, Inbred C57BL
dc.subjectMice, Transgenic
dc.subjectMice
dc.subjectVascular Endothelial Growth Factor A
dc.subjectNeuregulins
dc.subjectBone Morphogenetic Proteins
dc.subjectAdrenergic Agents
dc.subjectProteomics
dc.subjectSignal Transduction
dc.subjectThermogenesis
dc.subjectNeovascularization, Physiologic
dc.subjectModels, Biological
dc.subjectFemale
dc.subjectSubcutaneous Fat
dc.subjectAdipose Tissue, Brown
dc.subjectAdipocytes, Brown
dc.titleAdipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2018
prism.publicationNameNat Commun
prism.startingPage4974
prism.volume9
dc.identifier.doi10.17863/CAM.34512
dcterms.dateAccepted2018-10-22
rioxxterms.versionofrecord10.1038/s41467-018-07453-x
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-11-26
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.orcidSaez-Rodriguez, Julio [0000-0002-8552-8976]
dc.contributor.orcidVidal-Puig, Antonio [0000-0003-4220-9577]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Review
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idMedical Research Council (MC_UU_12012/2)
pubs.funder-project-idWellcome Trust (100574/Z/12/Z)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/J009865/1)
pubs.funder-project-idMedical Research Council (G0400192)
pubs.funder-project-idMedical Research Council (MC_UU_12012/5)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idMedical Research Council (G0600717)
pubs.funder-project-idMedical Research Council (G0802051)
pubs.funder-project-idMedical Research Council (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)
cam.issuedOnline2018-11-26


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