The evolving functions of the vasculature in regulating adipose tissue biology in health and obesity

Adipose tissue is an endocrine organ and a crucial regulator of energy storage and systemic metabolic homeostasis. Additionally, adipose tissue is a pivotal regulator of cardiovascular health and disease, mediated in part by the endocrine and paracrine secretion of several bioactive products, such as adipokines. Adipose vasculature has an instrumental role in the modulation of adipose tissue expansion, homeostasis and metabolism. The role of the adipose vasculature has been extensively explored in the context of obesity, which is recognized as a global health problem. Obesity-induced accumulation of fat, in combination with vascular rarefaction, promotes adipocyte dysfunction and induces oxidative stress, hypoxia and inflammation. It is now recognized that obesity-associated endothelial dysfunction often precedes the development of cardiovascular diseases. Investigations have revealed heterogeneity within the vascular niche and dynamic reciprocity between vascular and adipose cells, which can become dysregulated in obesity. Here we provide a comprehensive overview of the evolving functions of the vasculature in regulating adipose tissue biology in health and obesity. This Review emphasizes new insights into adipose tissue endothelial cell biology and alterations linked to obesity. In particular, studies highlighting the identification of adipose tissue endothelial cell heterogeneity, epigenetic factors, and plasticity of adipocytes and endothelial cells are presented. Advances in technology have uncovered the heterogeneity of the adipose tissue endothelium, revealing that it consists of canonical (venous, capillary, arterial, lymphatic) and adipose tissue-specific (pre-adipocytes, early progenitor endothelial cells, and immunomodulatory endothelial cells) vascular subpopulations.Adipose tissue endothelial phenotypes and gene transcription are governed by a plethora of transcription factors (and their post-translational modifications) and non-coding RNAs. Further investigation into transcriptional and epigenetic factors modulating adipose tissue endothelial phenotypes is warranted.The vasculature of adipose tissue serves as a bidirectional channel for lipids, immune cells, and adipokines. Furthermore, endothelial cells within this tissue maintain active communication with adjacent adipocytes, particularly through paracrine signals such as extracellular vesicles.Obesity correlates with disrupted blood flow in adipose tissue, endothelial dysfunction and reduced vascular density. These changes collectively lead to tissue hypoxia, inflammation and fibrosis.Vascular ageing and obesity-associated vascular malfunction exhibit several common characteristics. Rejuvenating the vasculature might hold the potential to counteract the metabolic deterioration associated with obesity.Obesity correlates with disturbances in the circadian rhythm of adipose tissue, which can trigger metabolic disorders; however, the chronobiology of adipose tissue endothelial cells is still largely unexplored.