Is the Adipose Tissue Vascular System a Therapeutic Target in the Era of Precision Medicine?

Changes in adipose tissue function, morphology, and secretome during obesity impair endothelial cell function and lead to persistent hypoxia and unresolved inflammation, which will contribute to whole-body endothelial dysfunction and chronic low-grade inflammation. Indeed, visceral fat dysfunction is more associated with insulin resistance than body mass index. Understanding the molecular landscape of visceral adipose tissue is pivotal to better comprehending an individual's metabolic health and even predicting future health outcomes. Single-cell studies are showing that the heterogeneity of the adipose depots relies not only on the diversity of cellular types, but also on the differential gene expression and secretome (even within the same cellular type). Adipose tissue cells respond in an orchestrated manner to adequate tissue plasticity to the current energetic needs, either by expanding or retracting. This response relies on coordinated regulation of adipocyte metabolism, angiogenesis, extracellular matrix remodeling, and short-term inflammation and oxidative stress. In this review, we look closely at cell intercommunication in the fat depot and discuss the main events occurring in adipose tissue associated with the progressive tissue dysfunction that happens in obesity: adipocyte metabolism, angiogenesis, and extracellular matrix remodeling. Furthermore, we discuss the modulation of angiogenesis as a potential therapeutic target in obesity by gathering relevant recent research and collectively discuss the metabolic implications of inhibiting or promoting angiogenesis at different stages of the metabolic sequelae of obesity.