Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue.
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Peer-reviewed
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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.
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2041-1723
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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)