TY  - JOUR
AU  - Hasan, Sana S
AU  - John, David
AU  - Rudnicki, Martina
AU  - AlZaim, Ibrahim
AU  - Eberhard, Daniel
AU  - Moll, Iris
AU  - Taylor, Jacqueline
AU  - Klein, Christian
AU  - von Heesen, Maximilian
AU  - Conradi, Lena-Christin
AU  - Adams, Ralf H
AU  - Lammert, Eckhard
AU  - Kalucka, Joanna
AU  - Ruhrberg, Christiana
AU  - Dimmeler, Stefanie
AU  - Fischer, Andreas
TI  - Obesity drives depot-specific vascular remodeling in male white adipose tissue.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-01289
SP  - 5392
PY  - 2025
N1  - Division Vascular Signaling and Cancer
AB  - 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.
KW  - Animals
KW  - Male
KW  - Obesity: metabolism
KW  - Obesity: pathology
KW  - Obesity: genetics
KW  - Adipose Tissue, White: metabolism
KW  - Adipose Tissue, White: pathology
KW  - Adipose Tissue, White: blood supply
KW  - Mice
KW  - Vascular Remodeling: genetics
KW  - Vascular Remodeling: physiology
KW  - Humans
KW  - Endothelial Cells: metabolism
KW  - Endothelial Cells: pathology
KW  - Vascular Endothelial Growth Factor A: metabolism
KW  - Vascular Endothelial Growth Factor A: genetics
KW  - Vascular Endothelial Growth Factor A: antagonists & inhibitors
KW  - Mice, Inbred C57BL
KW  - Subcutaneous Fat: metabolism
KW  - Subcutaneous Fat: pathology
KW  - Subcutaneous Fat: blood supply
KW  - Single-Cell Analysis
KW  - Disease Models, Animal
KW  - Intra-Abdominal Fat: metabolism
KW  - Endothelium, Vascular: metabolism
KW  - Endothelium, Vascular: pathology
KW  - Vascular Endothelial Growth Factor A (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40562785
DO  - DOI:10.1038/s41467-025-60910-2
UR  - https://inrepo02.dkfz.de/record/302263
ER  -