Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue.
View / Open Files
Authors
Pellegrinelli, Vanessa
Peirce, Vivian J
Howard, Laura
Virtue, Samuel
Türei, Dénes
Senzacqua, Martina
Dalley, Jeffrey W
Horton, Antony R
Bidault, Guillaume
Whittle, Andrew
Rahmouni, Kamal
Cinti, Saverio
Davies, Alun M
Vidal-Puig, Antonio
Publication Date
2018-11-26Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
9
Issue
1
Pages
4974
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic
Metadata
Show full item recordCitation
Pellegrinelli, V., Peirce, V. J., Howard, L., Virtue, S., Türei, D., Senzacqua, M., Frontini, A., et al. (2018). Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue.. Nat Commun, 9 (1), 4974. https://doi.org/10.1038/s41467-018-07453-x
Abstract
Activation 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.
Keywords
3T3-L1 Cells, Animals, Mice, Inbred C57BL, Mice, Transgenic, Mice, Vascular Endothelial Growth Factor A, Neuregulins, Bone Morphogenetic Proteins, Adrenergic Agents, Proteomics, Signal Transduction, Thermogenesis, Neovascularization, Physiologic, Models, Biological, Female, Subcutaneous Fat, Adipose Tissue, Brown, Adipocytes, Brown
Sponsorship
the American Heart Association (14EIA18860041) and the University of Iowa Fraternal Order of Eagles Diabetes Research Center.
Funder references
British Heart Foundation (None)
Medical Research Council (MC_UU_12012/2)
Wellcome Trust (100574/Z/12/Z)
Biotechnology and Biological Sciences Research Council (BB/J009865/1)
Medical Research Council (G0400192)
Medical Research Council (MC_UU_12012/5)
British Heart Foundation (None)
Medical Research Council (G0600717)
Medical Research Council (G0802051)
Medical Research Council (MC_G0802535)
MRC (MC_UU_00014/2)
MRC (MC_UU_00014/5)
British Heart Foundation (RG/18/7/33636)
Identifiers
External DOI: https://doi.org/10.1038/s41467-018-07453-x
This record's URL: https://www.repository.cam.ac.uk/handle/1810/287204
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: support@repository.cam.ac.uk