Exosomes in Metabolic Diseases: From Molecular Mechanisms to Clinical Applications

Exosomes, nanoscale vesicles secreted by diverse cell types, serve as critical mediators of intercellular and interorgan communication in metabolic physiology. Their unique advantages include encapsulating cell-specific biomolecules that reflect cellular origins, enabling noninvasive liquid biopsy for early disease detection through distinct signatures (e.g., miRNA profiles), and functioning as biocompatible drug delivery platforms or bioactive therapeutics in preclinical models. However, despite their transformative potential in metabolic disease diagnostics and therapy, a systematic synthesis of recent advances, molecular mechanisms, and clinical translation challenges is lacking. To address this gap, this review synthesizes cutting-edge insights into exosome biology—spanning composition, biogenesis, secretion, and tissue-specific roles in adipose, liver, muscle, and pancreas—and critically evaluates their dual diagnostic–therapeutic applications across obesity, diabetes, nonalcoholic fatty liver disease (NAFLD), and associated complications. We further delineate key translational hurdles (e.g., production scalability, cargo heterogeneity, and clinical validation) and propose strategies for standardization. By integrating interdisciplinary advances from nanotechnology, omics, and artificial intelligence (AI), this work provides a foundational framework to accelerate the clinical implementation of exosome-based approaches, ultimately advancing precision medicine for metabolic disorders.