Adipose-Derived Extracellular Vesicles and Intercellular Crosstalk With Skeletal Muscle: Implications for Sarcopenic Obesity and Metabolic Dysregulation.

Sarcopenic obesity, characterized by the concurrent presence of excess adiposity and diminished skeletal muscle mass and function, is closely linked to frailty, chronic inflammation, and insulin resistance. The increasing prevalence of sarcopenic obesity is driven by the global aging population, widespread adoption of sedentary lifestyles, and the ongoing obesity epidemic. Existing research describes a role for dysregulated crosstalk between adipose tissue and skeletal muscle tissue in driving sarcopenic obesity pathology, with recent evidence implying that extracellular vesicles (EVs, nano- to micro-scale, lipid bilayer membrane-delimited particles) have a significant role in facilitating intercellular communication to mediate critical tissue crosstalk. Given the significance of dysregulated tissue crosstalk in sarcopenic obesity pathology and the dysregulation of metabolism, the potential involvement of EVs has garnered considerable attention because of their scope as pharmacological targets and drug delivery vehicles, potentially leading to innovative therapeutic approaches. This review begins with an exploration of EV biology and the challenges associated with the standardization and execution of EV research. It then examines the impact of sarcopenic obesity risk factors on circulating and adipose-derived EV profiles. Current understanding of the role of specific EV cargo, including microRNAs, proteins, and lipids, in mediating crosstalk between adipose tissue and skeletal muscle is critically evaluated. Finally, the potential of EV-based therapeutics for treating sarcopenic obesity is discussed, along with recommendations for future research directions.