Neurovascular Impairment in Type 2 Diabetes Mellitus: The Role of Adipocyte-Derived Exosomes.

Type 2 diabetes mellitus (T2DM) is a major metabolic disorder characterized by chronic hyperglycemia with far-reaching morbidities. Among these, diabetes-related cerebrovascular complications such as ischemic and hemorrhagic stroke, cerebral blood vessel disease, and vascular dementia are significant contributors to morbidity and mortality. Adipose tissue is a metabolically active endocrine organ that becomes dysfunctional in T2DM and communicates with distant tissues via secreted factors, including extracellular vesicles such as exosomes (EXs), phospholipid bilayer-enclosed nanosized particles. These adipocyte-derived exosomes (Ad-EXs) carry bioactive cargo, including lipids, proteins, and microRNAs that influence the function of distant organs, including the brain. Evidence indicates that Ad-EXs in T2DM are a significant risk factor for cerebrovascular complications via neurovascular impairment either directly through the adipose tissue-brain axis or indirectly by other organs. This review provides an overview of current knowledge on how Ad-EXs from different adipocyte populations contribute to cerebrovascular complications through oxidative stress, blood-brain barrier disruption, neuroinflammation, and mitochondrial dysfunction. Particular emphasis is placed on recent findings and gaps in knowledge linking diabetic Ad-EXs with brain microvascular endothelial cells that mediate neurovascular crosstalk, contributing to stroke susceptibility and cognitive decline. We also discuss the potential of Ad-EXs as biomarkers and therapeutic targets for cerebrovascular complications of T2DM.