The interplay between exosomal miRNAs and cytokine networks in metabolic diseases.

Exosomal microRNAs (miRNAs) are increasingly recognized as central regulators of metabolic pathways, influencing glucose homeostasis, lipid metabolism, and inflammatory responses. Their ability to mediate inter-organ communication positions them as both biomarkers and therapeutic candidates for metabolic diseases such as type 2 diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD). This review synthesizes recent literature on the mechanistic roles of exosomal miRNAs in metabolic regulation, their influence on insulin sensitivity and lipid homeostasis, and their interaction with cytokine networks. It also evaluates current approaches in exosome engineering, including miRNA enrichment, surface modification, and CRISPR/Cas9-based editing, as well as emerging high-throughput technologies for profiling exosomal miRNAs. Exosomal miRNAs modulate insulin signaling, lipid catabolism, adipogenesis, and inflammatory responses, thereby contributing to metabolic adaptation and disease progression. Specific miRNAs, such as miR-122, miR-155, and miR-34a, have been implicated in obesity, diabetes, and NAFLD, serving as both biomarkers and therapeutic targets. Advances in exosome engineering and delivery strategies have demonstrated improved specificity, stability, and therapeutic efficacy. High-throughput sequencing and single-vesicle analyses provide insights into the heterogeneity and dynamics of exosomal miRNAs, supporting their clinical translation. Exosomal miRNAs represent promising tools for diagnosis and therapy in metabolic disorders. Their dual role as regulators of metabolic processes and carriers of therapeutic cargo underscores their potential in precision medicine. Future integration of bioengineering, CRISPR-based modulation, and omics-driven predictive modeling will enhance their translational applicability, paving the way for personalized therapies in metabolic diseases.