Liver-derived Exosomal miRNA in NAFLD: Mechanisms of Action, Biomarkers, and Therapeutic Applications

Nonalcoholic fatty liver disease (NAFLD) is of global concern due to its high prevalence worldwide. NAFLD, as one of the most common causes of liver function abnormalities, is associated with obesity, insulin resistance, and type 2 diabetes mellitus, and there are no medications available to treat NAFLD. Extracellular vesicles (EVs) are nanosized, membrane-bound vesicles that deliver biomolecules between cells. Exosomes are a subtype of EVs that mediate intercellular communication by delivering proteins and RNAs. MicroRNAs (miRNAs) are a highly conserved class of small tissue-specific non-coding RNAs that influence the expression of many functionally interacting genes. Hepatic-derived exosomal miRNAs are tightly associated with NAFLD occurrence and progression through multiple mechanisms. In addition, the characterization of miRNAs suggests that they may serve as multifunctional biomarkers for NAFLD, be used as clinical therapeutic targets for NAFLD, and be significant predictors of patient prognosis. Here, we review recent advances in the regulation and function of exosome- derived miRNAs in NAFLD, focusing on miRNAs specifically expressed or enriched in hepatocytes (HCs), hepatic macrophages, hepatic stellate cells (HSCs), and other immune cells in the liver. Finally, we discuss future research directions on exosomal miRNAs as biomarkers for NAFLD's diagnosis and clinical therapeutic targets.