Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue.
Peirce, Vivian J
Horton, Antony R
Davies, Alun M
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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.. Nature communications, 9 (1), 4974. https://doi.org/10.1038/s41467-018-07453-x
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.
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
the American Heart Association (14EIA18860041) and the University of Iowa Fraternal Order of Eagles Diabetes Research Center.
British Heart Foundation (RG/12/13/29853)
Wellcome Trust (100574/Z/12/Z)
British Heart Foundation (PG/12/53/29714)
British Heart Foundation (RG/18/7/33636)
External DOI: https://doi.org/10.1038/s41467-018-07453-x
This record's URL: https://www.repository.cam.ac.uk/handle/1810/287204
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/