Abstract

Adipose tissue is now recognized as a complex immuno-endocrine organ that communicates with distant 
metabolic tissues through hormones, lipids and, increasingly appreciated, extracellular vesicles (EVs). In obesity, 
expanding adipose depots become inflamed, hypoxic and fibrotic, and this dysfunctional state is accompanied by 
a marked quantitative and qualitative shift in adipose-derived EVs released into the circulation. These vesicles, 
which include exosomes and microvesicles from adipocytes, adipose tissue macrophages (ATMs) and stromal 
cells, carry bioactive cargo such as microRNAs, proteins, lipids and mitochondrial fragments that modulate 
insulin signaling, inflammation and cell survival in liver, skeletal muscle, pancreatic islets and vasculature. 
Accumulating evidence indicates that EVs from obese adipose tissue can induce insulin resistance and glucose 
intolerance when transferred to lean animals or to naïve cells in vitro, and that specific miRNAs and proteins 
within these vesicles are sufficient to drive key features of the obese–diabetic phenotype. ATM-derived exosomal 
miRNAs such as miR-155 and miR-29a promote insulin resistance across liver, muscle and adipose tissue, while 
adipocyte-derived EVs polarize macrophages toward pro-inflammatory states, establishing a vicious cycle of 
adipose inflammation and systemic metabolic dysfunction.This review focuses on EVs from obese adipose tissue 
as “hidden messengers” in the early pathogenesis of type 2 diabetes (T2D). We outline EV biogenesis and the 
cellular sources of adipose EVs, describe how obesity remodels their cargo and release, and synthesize data on 
EV-mediated crosstalk with liver, muscle, β-cells and vascular cells. We then discuss emerging evidence that 
adipose EV signatures can serve as minimally invasive biomarkers of transition from obesity to T2D, and 
highlight therapeutic strategies that either normalize pathogenic adipose EV output or harness protective EVs 
from adipose-derived stem cells. Finally, we consider key challenges in translating EV biology into clinical tools, 
including issues of specificity, standardization and safety.