A REVIEW ON EXOSOME-MEDIATED INTER-ORGAN COMMUNICATION IN METABOLIC DISEASES: A CONCEPTUAL FRAMEWORK-LINKING KEY METABOLIC TISSUES FOR THERAPEUTIC APPLICATIONS

Recent years have seen increasing recognition of metabolic diseases like type 2 diabetes mellitus (T2DM), obesity, and non-alcoholic fatty liver disease (NAFLD) as systemic disorders characterized by aberrant inter-organ communications. As vesicles that include miRNAs, proteins, lipids, and metabolites, exosomes have been demonstrated as an important mechanism underlying the inter-organ communications. This review critically analyzes the evidence for exosome-dependent signals between liver, pancreas, skeletal muscle, adipose tissue, and intestine – the five major metabolic tissues – in regulating insulin sensitivity, lipid metabolism, inflammation, and energy metabolism. While the importance of the tissue-specific exosomal components in metabolism is well-documented in experimental studies, the level of evidence has not been convincing, especially due to its reliance on pre-clinical models. Specifically, miRNAs found in exosomes like miR-122 and miR-375 have been proposed as biomarkers for various metabolic disorders; yet, their diagnostic value has not been validated in clinical populations due to low reproducibility. Engineered exosomes are currently explored for delivering therapy. Still, the efficacy of these approaches is hindered by various technical obstacles. This review provides an overview of the existing evidence on exosomes’ role in metabolism and draws the line between verified and speculative mechanisms.