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Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice

Author

Listed:
  • Cheukyau Luk

    (University of Leeds)

  • Katherine I. Bridge

    (University of Leeds)

  • Nele Warmke

    (University of Leeds
    Max Delbrück Center for Molecular Medicine in the Helmholtz Association)

  • Katie J. Simmons

    (University of Leeds
    University of Leeds)

  • Michael Drozd

    (University of Leeds)

  • Amy Moran

    (University of Leeds)

  • Amanda D. V. MacCannell

    (University of Leeds)

  • Chew W. Cheng

    (University of Leeds)

  • Sam Straw

    (University of Leeds)

  • Jason L. Scragg

    (University of Leeds)

  • Jessica Smith

    (University of Leeds)

  • Claire H. Ozber

    (University of Leeds
    University of Leeds)

  • Chloe G. Wilkinson

    (University of Leeds
    Oxford Road)

  • Anna Skromna

    (University of Leeds)

  • Natallia Makava

    (University of Leeds)

  • Hiran A. Prag

    (University of Cambridge, Cambridge Biomedical Campus)

  • T. Simon Futers

    (University of Leeds)

  • Oliver I. Brown

    (University of Leeds)

  • Alexander-Francisco Bruns

    (University of Leeds)

  • Andrew MN Walker

    (University of Leeds)

  • Nicole T. Watt

    (University of Leeds)

  • Romana Mughal

    (University of Leeds
    University of Huddersfield)

  • Kathryn J. Griffin

    (University of Leeds)

  • Nadira Y. Yuldasheva

    (University of Leeds)

  • Sunti Limumpornpetch

    (University of Leeds
    Faculty of Medicine Prince of Songkla University)

  • Hema Viswambharan

    (University of Leeds)

  • Piruthivi Sukumar

    (University of Leeds)

  • David J. Beech

    (University of Leeds)

  • Antonio Vidal-Puig

    (University of Cambridge Metabolic Research Laboratories)

  • Klaus K. Witte

    (University of Leeds)

  • Michael P. Murphy

    (University of Cambridge, Cambridge Biomedical Campus)

  • Richard C. Hartley

    (University of Glasgow)

  • Stephen B. Wheatcroft

    (University of Leeds)

  • Richard M. Cubbon

    (University of Leeds)

  • Lee D. Roberts

    (University of Leeds)

  • Mark T. Kearney

    (University of Leeds)

  • Natalie J. Haywood

    (University of Leeds)

Abstract

During recent decades, changes in lifestyle have led to widespread nutritional obesity and its related complications. Remodelling adipose tissue as a therapeutic goal for obesity and its complications has attracted much attention and continues to be actively explored. The endothelium lines all blood vessels and is close to all cells, including adipocytes. The endothelium has been suggested to act as a paracrine organ. We explore the role of endothelial insulin-like growth factor-1 receptor (IGF-1R), as a paracrine modulator of white adipose phenotype. We show that a reduction in endothelial IGF-1R expression in the presence of high-fat feeding in male mice leads to depot-specific beneficial white adipose tissue remodelling, increases whole-body energy expenditure and enhances insulin sensitivity via a non-cell-autonomous paracrine mechanism. We demonstrate that increased endothelial malonate may be contributory and that malonate prodrugs have potentially therapeutically relevant properties in the treatment of obesity-related metabolic disease.

Suggested Citation

  • Cheukyau Luk & Katherine I. Bridge & Nele Warmke & Katie J. Simmons & Michael Drozd & Amy Moran & Amanda D. V. MacCannell & Chew W. Cheng & Sam Straw & Jason L. Scragg & Jessica Smith & Claire H. Ozbe, 2025. "Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-54669-1
    DOI: 10.1038/s41467-024-54669-1
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