Obesity Alters the Vascular Morphology and VEGF-A Signaling in Adipose Tissue

Abstract

Obesity is a global health crisis, with its prevalence particularly severe in the United States, where over 42% of adults live with obesity. Obesity is driven by complex molecular and tissue-level mechanisms that remain poorly understood. Among these, angiogenesis—primarily mediated by vascular endothelial growth factor-A (VEGF-A)—is critical for adipose tissue expansion but presents unique challenges for therapeutic targeting due to its intricate regulation. Systems biology approaches have advanced our understanding of VEGF-A signaling in vascular diseases, but their application to obesity is limited by scattered and sometimes contradictory data. To address this gap, we performed a comprehensive analysis of the existing literature to synthesize key findings, standardize data, and provide a holistic perspective on the adipose vascular microenvironment. The data mining revealed five key findings: (1) obesity increases adipocyte size by 78%; (2) vessel density in adipose tissue decreases by 51% in mice with obesity, with vessels being 47%–58% smaller and four to nine times denser in comparison with tumor vessels; (3) capillary basement membrane thickness remains similar regardless of obesity; (4) VEGF-A shows the strongest binding affinity for VEGFR1, with four times stronger affinity for VEGFR2 than for NRP1; and (5) binding affinities measured by radioligand binding assay and surface plasmon resonance are significantly different. These consolidated findings provide essential parameters for systems biology modeling, new insights into obesity-induced changes in adipose tissue, and a foundation for developing angiogenesis-targeting therapies for obesity.