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

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.