Adipose tissue-derived extracellular vesicles as drivers of endothelial dysfunction in obesity

Abstract

Obesity and (white) adipose tissue (AT) inflammation are closely linked to endothelial dysfunction (ED) and neurological conditions associated with an impaired blood-brain barrier (BBB). AT-derived extracellular vesicles (AT-EVs), cell-derived particles involved in intercellular and interorgan communication, have emerged as active mediators of this process, yet the underlying mechanisms remain largely elusive. Molecular and functional profiling of AT-EVs' cargo has revealed obesity-related changes in miRNAs, proteins, and lipids that drive ED, primarily by activating proinflammatory signaling in endothelial cells. Importantly, these cargo changes in AT-EVs suggest a broader role, potentially modulating the neurovascular unit, thereby linking AT-EVs to brain pathologies. Collectively, these insights highlight AT-EVs as critical players in obesity-related ED and support their causal role in promoting neurological disease progression.