Molecular mechanisms linking adipose tissue-derived small extracellular vesicles/exosomes to the development or amelioration of obesity, insulin resistance, and diabetes-related complications.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by impaired glucose storage and utilization in adipose tissue and skeletal muscle. Type 2 diabetes mellitus (T2DM) is particularly prevalent among individuals with obesity, as excess weight fosters significant health complications, including inflammation and insulin resistance, ultimately contributing to the development of T2DM. It is believed that the crosstalk between adipose tissue, skeletal muscle, and the endocrine pancreas underlies the glucose dysmetabolism associated with excess weight. Extracellular vesicles (EVs) can play a role in mediating intercellular crosstalk and could be involved in the pathogenesis of T2DM and related complications in individuals with obesity. Exosomes/small EVs (sEVs) derived from adipose tissue may contribute to either the progression or management of metabolic syndromes, primarily through their effects on insulin resistance. Hence, the current narrative review was designed to evaluate the effect of adipose-derived sEVs in insulin resistance and its related complications. These sEVs have been isolated from white adipose tissue (WAT), brown adipose tissue (BAT), adipose-derived stem cells (ADSCs), adipose tissue macrophages (ATMs), as well as from plasma and other tissues of obese individuals and animal models. The present review showed that sEVs derived from adipose tissue and/or obese individuals and animal models may contribute significantly to the onset and enhancement of insulin resistance. However, sEVs extracted from ADSCs of healthy adipose tissue could enhance insulin sensitivity via their bioactive components (e.g., microRNAs). Additional complementary studies are required to validate the dual role of adipose-derived sEVs on the amelioration or progression of insulin resistance-related complications.