Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue PMID: 30478315

ADC Targets in Oncology

2026-04-10

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

1. Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, CB2 0QQ, UK. [email protected].
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. [email protected].
13. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. [email protected].

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.