Adipose-derived extracellular vesicle miRNAs: multifunctional regulators of brain function

Adipose tissue is increasingly recognized as a highly heterogeneous secretory organ, and the extracellular vesicle-associated microRNAs (EV-miRNAs) it releases can act as peripheral molecular signals involved in long-distance regulation. Current evidence indicates that adipose-derived EV-miRNAs exhibit pronounced adipose depot- and cell-of-origin specificity, and that their composition can be dynamically altered by metabolic state. Following biogenesis and selective sorting, these miRNAs can be transported through the circulation within EVs and, under certain conditions, gain access to the central nervous system (CNS). Functional studies have shown that adipose-derived EV-miRNAs primarily act on neurons and, in some pathological models, modulate microglial function, thereby contributing to the regulation of hypothalamic energy homeostasis, learning and memory, emotional and stress-related responses, and neuroimmune processes. Obesity further remodels the adipose-derived EV-miRNA repertoire, enhancing pathological miRNA signals while concomitantly reducing certain homeostatic miRNA signals, thereby altering their regulatory effects on the central nervous system. This review systematically summarizes the tissue and cellular origins, biogenesis and selective sorting, circulatory transport and central delivery of adipose-derived EV-miRNAs, as well as their regulatory effects across multiple dimensions of brain function. Collectively, adipose-derived EV-miRNAs constitute an important molecular signaling layer through which adipose tissue states influence brain function; however, their source-specific profiles under physiological conditions, mechanisms of brain region- and cell-specific targeting, and causal roles and translational potential in human disease remain to be further elucidated.