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

Pellegrinelli, Vanessa, Peirce, Vivian J., Howard, Laura, Virtue, Samuel, Türei, Dénes, Senzacqua, Martina, Frontini, Andrea, Dalley, Jeffrey W., Horton, Antony R., Bidault, Guillaume, Severi, Ilenia, Whittle, Andrew, Rahmouni, Kamal, Saez-Rodriguez, Julio, Cinti, Saverio, Davies, Alun M. ORCID: https://orcid.org/0000-0001-5841-8176 and Vidal-Puig, Antonio 2018. Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue. Nature Communications 9 , 4974. 10.1038/s41467-018-07453-x

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License.
Publisher:	Nature Research
ISSN:	2041-1723
Date of First Compliant Deposit:	27 November 2018
Date of Acceptance:	22 October 2018
Last Modified:	06 May 2023 12:19
URI:	https://orca.cardiff.ac.uk/id/eprint/117117

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