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

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, Eckhard Lammert, Joanna Kalucka, Christiana Ruhrberg, Stefanie Dimmeler and Andreas Fischer ()
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Sana S. Hasan: University Medical Center Göttingen
David John: Goethe University
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
Joanna Kalucka: Aarhus University
Christiana Ruhrberg: University College London
Stefanie Dimmeler: Goethe University
Andreas Fischer: University Medical Center Göttingen

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-60910-2

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