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Obesity drives depot-specific vascular remodeling in male white adipose tissue

Author

Listed:
  • Sana S. Hasan

    (University Medical Center Göttingen)

  • David John

    (Goethe University
    Cardio-Pulmonary Institute (CPI))

  • Martina Rudnicki

    (University College London)

  • Ibrahim AlZaim

    (Aarhus University)

  • Daniel Eberhard

    (Institute of Metabolic Physiology)

  • Iris Moll

    (German Cancer Research Center (DKFZ))

  • Jacqueline Taylor

    (German Cancer Research Center (DKFZ))

  • Christian Klein

    (Roche Glycart AG)

  • Maximilian von Heesen

    (University Medical Center Göttingen)

  • Lena-Christin Conradi

    (University Medical Center Göttingen)

  • Ralf H. Adams

    (Max Planck Institute for Molecular Biomedicine)

  • Eckhard Lammert

    (Institute of Metabolic Physiology
    Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf
    German Center for Diabetes Research (DZD e.V.))

  • Joanna Kalucka

    (Aarhus University)

  • Christiana Ruhrberg

    (University College London)

  • Stefanie Dimmeler

    (Goethe University
    Cardio-Pulmonary Institute (CPI)
    German Center for Cardiovascular Research (DZHK))

  • Andreas Fischer

    (University Medical Center Göttingen
    partner site Lower Saxony)

Abstract

Obesity-driven pathological expansion of white adipose tissue (WAT) is a key driver of endothelial dysfunction. However, early vascular alterations associated with over-nutrition also serve to exacerbate WAT dysfunction. Here, we conduct a single-cell transcriptomic analysis of WAT endothelium to delineate endothelial heterogeneity and elucidate vascular alterations and its consequence in a male murine model of obesity. We demarcate depot-specific differences in subcutaneous (sWAT) and visceral WAT (vWAT) endothelium through in sillico analysis and further corroboration of our findings. Moreover, we identify a sWAT-specific fenestrated endothelial cell (EC) subtype, which declines in obese conditions. Utilizing systemic anti-VEGFA blockade and genetic Vegfa manipulation, we demonstrate that VEGFA is necessary for maintaining fenestration in sWAT. Additionally, we detect this fenestrated EC subtype in male human WAT, which undergoes reduction in individuals with obesity. Collectively, this atlas serves as a valuable tool for future studies to decipher the functional significance of different WAT EC subtypes.

Suggested Citation

  • Sana S. Hasan & David John & Martina Rudnicki & Ibrahim AlZaim & Daniel Eberhard & Iris Moll & Jacqueline Taylor & Christian Klein & Maximilian von Heesen & Lena-Christin Conradi & Ralf H. Adams & Eck, 2025. "Obesity drives depot-specific vascular remodeling in male white adipose tissue," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60910-2
    DOI: 10.1038/s41467-025-60910-2
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    References listed on IDEAS

    as
    1. Fei Wang & Peiwen Ding & Xue Liang & Xiangning Ding & Camilla Blunk Brandt & Evelina Sjöstedt & Jiacheng Zhu & Saga Bolund & Lijing Zhang & Laura P. M. H. Rooij & Lihua Luo & Yanan Wei & Wandong Zhao , 2022. "Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Fei Wang & Peiwen Ding & Xue Liang & Xiangning Ding & Camilla Blunk Brandt & Evelina Sjöstedt & Jiacheng Zhu & Saga Bolund & Lijing Zhang & Laura P. M. H. Rooij & Lihua Luo & Yanan Wei & Wandong Zhao , 2022. "Author Correction: Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level," Nature Communications, Nature, vol. 13(1), pages 1-2, December.
    3. Margo P. Emont & Christopher Jacobs & Adam L. Essene & Deepti Pant & Danielle Tenen & Georgia Colleluori & Angelica Vincenzo & Anja M. Jørgensen & Hesam Dashti & Adam Stefek & Elizabeth McGonagle & So, 2022. "A single-cell atlas of human and mouse white adipose tissue," Nature, Nature, vol. 603(7903), pages 926-933, March.
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