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

Vanessa Pellegrinelli (), Vivian J. Peirce, Laura Howard, Samuel Virtue, Dénes Türei, Martina Senzacqua, Andrea Frontini, Jeffrey W. Dalley, Antony R. Horton, Guillaume Bidault, Ilenia Severi, Andrew Whittle, Kamal Rahmouni, Julio Saez-Rodriguez, Saverio Cinti, Alun M. Davies and Antonio Vidal-Puig ()
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Vanessa Pellegrinelli: University of Cambridge
Vivian J. Peirce: University of Cambridge
Laura Howard: Cardiff University
Samuel Virtue: University of Cambridge
Dénes Türei: Structural and Computational Biology Unit
Martina Senzacqua: Università Politecnica delle Marche
Andrea Frontini: University of Pavia
Jeffrey W. Dalley: University of Cambridge
Antony R. Horton: Cardiff University
Guillaume Bidault: University of Cambridge
Ilenia Severi: Università Politecnica delle Marche
Andrew Whittle: University of Cambridge
Kamal Rahmouni: University of Iowa
Julio Saez-Rodriguez: European Bioinformatics Institute (EBI)
Saverio Cinti: Università Politecnica delle Marche
Alun M. Davies: Cardiff University
Antonio Vidal-Puig: University of Cambridge

Nature Communications, 2018, vol. 9, issue 1, 1-18

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07453-x

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