Journal Article

DKFZ-2025-01289

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Obesity drives depot-specific vascular remodeling in male white adipose tissue.

Hasan, S. S. ; John, D. ; Rudnicki, M. ; AlZaim, I. ; Eberhard, D. ; Moll, I.DKFZ* ; Taylor, J.DKFZ* ; Klein, C. ; von Heesen, M. ; Conradi, L.-C. ; Adams, R. H. ; Lammert, E. ; Kalucka, J. ; Ruhrberg, C. ; Dimmeler, S. ; Fischer, A.

2025
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41467-025-60910-2

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.

Keyword(s): Animals (MeSH) ; Male (MeSH) ; Obesity: metabolism (MeSH) ; Obesity: pathology (MeSH) ; Obesity: genetics (MeSH) ; Adipose Tissue, White: metabolism (MeSH) ; Adipose Tissue, White: pathology (MeSH) ; Adipose Tissue, White: blood supply (MeSH) ; Mice (MeSH) ; Vascular Remodeling: genetics (MeSH) ; Vascular Remodeling: physiology (MeSH) ; Humans (MeSH) ; Endothelial Cells: metabolism (MeSH) ; Endothelial Cells: pathology (MeSH) ; Vascular Endothelial Growth Factor A: metabolism (MeSH) ; Vascular Endothelial Growth Factor A: genetics (MeSH) ; Vascular Endothelial Growth Factor A: antagonists & inhibitors (MeSH) ; Mice, Inbred C57BL (MeSH) ; Subcutaneous Fat: metabolism (MeSH) ; Subcutaneous Fat: pathology (MeSH) ; Subcutaneous Fat: blood supply (MeSH) ; Single-Cell Analysis (MeSH) ; Disease Models, Animal (MeSH) ; Intra-Abdominal Fat: metabolism (MeSH) ; Endothelium, Vascular: metabolism (MeSH) ; Endothelium, Vascular: pathology (MeSH) ; Vascular Endothelial Growth Factor A

Note: Division Vascular Signaling and Cancer

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Contributing Institute(s):

1. Vaskuläre Signaltransduktion und Krebs (A270)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2025

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