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Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue.

Published version
Peer-reviewed

Type

Article

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Authors

Pellegrinelli, Vanessa 
Peirce, Vivian J 
Howard, Laura 
Virtue, Samuel 
Türei, Dénes 

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.

Description

Keywords

3T3-L1 Cells, Adipocytes, Brown, Adipose Tissue, Brown, Adrenergic Agents, Animals, Bone Morphogenetic Proteins, Female, Mice, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Neovascularization, Physiologic, Neuregulins, Proteomics, Signal Transduction, Subcutaneous Fat, Thermogenesis, Vascular Endothelial Growth Factor A

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

9

Publisher

Springer Science and Business Media LLC
Sponsorship
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)
European Commission (222639)
Medical Research Council (MC_PC_12012)
Medical Research Council (G0600717/1)
the American Heart Association (14EIA18860041) and the University of Iowa Fraternal Order of Eagles Diabetes Research Center.