2. Academic Validation
  3. Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue

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.
Vanessa Pellegrinelli 1,  Vivian J Peirce 2,  Laura Howard 3,  Samuel Virtue 2,  Dénes Türei 4 5 6,  Martina Senzacqua 7,  Andrea Frontini 8,  Jeffrey W Dalley 9 10,  Antony R Horton 3,  Guillaume Bidault 2,  Ilenia Severi 7,  Andrew Whittle 2,  Kamal Rahmouni 11,  Julio Saez-Rodriguez 5 6,  Saverio Cinti 7,  Alun M Davies 3,  Antonio Vidal-Puig 12 13
Affiliations

Affiliations

  • 1 Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, CB2 0QQ, UK. vp332@medschl.cam.ac.uk.
  • 2 Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, CB2 0QQ, UK.
  • 3 School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AT, UK.
  • 4 European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, D-69117, Heidelberg, Germany.
  • 5 European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute (EBI), Cambridge, CB10 1SD, UK.
  • 6 RWTH Aachen University, Faculty of Medicine, Joint Research Centre for Computational Biomedicine, MTI2 Wendlingweg 2, D-52074, Aachen, Germany.
  • 7 Department of Experimental and Clinical Medicine, Center of Obesity, Università Politecnica delle Marche, 60126, Ancona, Italy.
  • 8 Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100, Pavia, Italy.
  • 9 Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK.
  • 10 Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.
  • 11 Department of Pharmacology, University of Iowa, Iowa City, IA, 52242, USA.
  • 12 Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, CB2 0QQ, UK. ajv22@medschl.cam.ac.uk.
  • 13 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. ajv22@medschl.cam.ac.uk.
PMID: 30478315 DOI: 10.1038/s41467-018-07453-x
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.

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