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

Nat Commun. 2018 Nov 26;9(1):4974. doi: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Adrenergic Agents
  • Bmp8b protein, mouse
  • Bone Morphogenetic Proteins
  • Neuregulins
  • Vascular Endothelial Growth Factor A
  • neuregulin-4