Extracellular vesicles in metabolic dysfunction-associated steatotic liver disease: From intercellular signaling to clinical translation.

Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a substantial global health burden, progressing from simple steatosis to metabolic dysfunction-associated steatohepatitis and cirrhosis. A deeper understanding of the underlying mechanisms and associated complications is crucial for developing effective therapies. Extracellular vesicles (EVs), nanoscale membrane-enclosed particles carrying bioactive cargoes such as proteins and noncoding RNAs, including microRNAs and long noncoding RNAs, play crucial roles in intercellular communication and have emerged as critical mediators of MASLD pathogenesis. This article details the current understanding of the function of EVs in MASLD progression, emphasizing specific cell-derived EVs implicated in disease development. We elucidate how EVs facilitate intercellular communication and influence key pathological processes, including lipotoxicity, inflammation, and fibrosis. Furthermore, we examine the involvement of EVs in MASLD-associated complications and evaluate their potential as minimally invasive tools for disease diagnosis, staging, and prognosis. We also explore EV-based therapeutic strategies, encompassing preclinical studies, while acknowledging current challenges and future opportunities. Finally, we discuss emerging research trends, the potential for personalized medicine, and areas necessitating further investigation, particularly the utilization of EVs as therapeutic targets or delivery vehicles. This review underscores the pivotal role of EVs in MASLD, providing insights into their translational potential for improved patient outcomes.