Molecular smugglers in obesity-driven MASLD: Snitching on adipose-derived extracellular vesicles

Obesity-related adipose tissue (AT) dysfunction is closely associated with the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver disease. Emerging evidence highlights that the AT-liver crosstalk is mediated by AT-derived extracellular vesicles (EVs) that exacerbate the progression of MASLD during obesity. During obesity development, AT undergoes pathological remodeling characterized by hypertrophic adipocytes, pro-inflammatory macrophages, dysfunctional adipose-derived stem cells (ADSCs), and increased cellular heterogeneity, which collectively alter the composition and function of secreted EVs. AT-derived EVs enter the circulation and transport bioactive cargo, including microRNAs (miRNAs), mtDNA, proteins and lipids to the liver, where they can modulate hepatocellular metabolism, liver inflammation and fibrogenesis. This review outlines the current state of knowledge on AT-derived EVs during MASLD, emphasizing the dynamic changes in AT under metabolic stress as well as the interactions between AT-derived EVs and the liver. We further explore the potential of EVs and their associated molecules as noninvasive biomarkers and potential therapeutic targets and underscore that understanding AT-liver communication via EVs offers perspectives for precision medicine in MASLD.