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; Antonio Vidal-Puig

doi:10.1038/s41467-018-07453-x

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

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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, …

Nature communications, Vol.9(1), pp.1-18

12/01/2018

DOI: 10.1038/s41467-018-07453-x

PMID: 30478315

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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. Enhancing thermogenesis is a promising therapeutic strategy for promoting metabolic health. Here the authors show that adipocyte-secreted BMP8b contributes to optimizing the thermogenic response by remodeling of the neuro-vascular networks in brown and white adipose tissue.

Details

Title: Subtitle: Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue
Creators: Vanessa Pellegrinelli - Cambridge, CB2 0QQ UK
Vivian J Peirce - Cambridge, CB2 0QQ UK
Laura Howard - Museum Avenue, Cardiff, CF10 3AT UK
Samuel Virtue - Cambridge, CB2 0QQ UK
Dénes Türei - Meyerhofstrasse 1, D-69117 Heidelberg, Germany
Martina Senzacqua - 60126 Ancona, Italy
Andrea Frontini - 27100 Pavia, Italy
Jeffrey W Dalley - Downing Street, Cambridge, CB2 3EB UK
Antony R Horton - Museum Avenue, Cardiff, CF10 3AT UK
Guillaume Bidault - Cambridge, CB2 0QQ UK
Ilenia Severi - 60126 Ancona, Italy
Andrew Whittle - Cambridge, CB2 0QQ UK
Kamal Rahmouni - Iowa City, IA 52242 USA
Julio Saez-Rodriguez - Cambridge, CB10 1SD UK
Saverio Cinti - 60126 Ancona, Italy
Alun M Davies - Museum Avenue, Cardiff, CF10 3AT UK
Antonio Vidal-Puig - Cambridge, CB2 0QQ UK
Resource Type: Journal article
Publication Details: Nature communications, Vol.9(1), pp.1-18
DOI: 10.1038/s41467-018-07453-x
PMID: 30478315
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Publisher: Nature Publishing Group UK; London
Language: English
Date published: 12/01/2018
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040345802771

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