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

Author

Listed:
  • 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
    European Bioinformatics Institute (EBI)
    Joint Research Centre for Computational Biomedicine)

  • Martina Senzacqua

    (Università Politecnica delle Marche)

  • Andrea Frontini

    (University of Pavia)

  • Jeffrey W. Dalley

    (University of Cambridge
    Addenbrooke’s Hospital)

  • 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)
    Joint Research Centre for Computational Biomedicine)

  • Saverio Cinti

    (Università Politecnica delle Marche)

  • Alun M. Davies

    (Cardiff University)

  • Antonio Vidal-Puig

    (University of Cambridge
    Wellcome Trust Genome Campus)

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.

Suggested Citation

  • 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 &, 2018. "Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue," Nature Communications, Nature, vol. 9(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07453-x
    DOI: 10.1038/s41467-018-07453-x
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    Cited by:

    1. Elisa Duregotti & Christina M. Reumiller & Ursula Mayr & Maria Hasman & Lukas E. Schmidt & Sean A. Burnap & Konstantinos Theofilatos & Javier Barallobre-Barreiro & Arne Beran & Maria Grandoch & Alessa, 2022. "Reduced secretion of neuronal growth regulator 1 contributes to impaired adipose-neuronal crosstalk in obesity," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Lai Yee Cheong & Baile Wang & Qin Wang & Leigang Jin & Kelvin H. M. Kwok & Xiaoping Wu & Lingling Shu & Huige Lin & Sookja Kim Chung & Kenneth K. Y. Cheng & Ruby L. C. Hoo & Aimin Xu, 2023. "Fibroblastic reticular cells in lymph node potentiate white adipose tissue beiging through neuro-immune crosstalk in male mice," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Tatsuya Yoshizawa & Yoshifumi Sato & Shihab U. Sobuz & Tomoya Mizumoto & Tomonori Tsuyama & Md. Fazlul Karim & Keishi Miyata & Masayoshi Tasaki & Masaya Yamazaki & Yuichi Kariba & Norie Araki & Eiichi, 2022. "SIRT7 suppresses energy expenditure and thermogenesis by regulating brown adipose tissue functions in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Sujun Yan & Xiaoling Zhou & Canlan Wu & Yunyi Gao & Yu Qian & Jingyu Hou & Renxiang Xie & Bing Han & Zhanghui Chen & Saisai Wei & Xiangwei Gao, 2023. "Adipocyte YTH N(6)-methyladenosine RNA-binding protein 1 protects against obesity by promoting white adipose tissue beiging in male mice," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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