Project R-16004

Message in a bubble: adipocyte-derived mitochondrial extracellular vesicles as metabolic regulators in obesity-related insulin resistance (Research)

Obesity and type 2 diabetes mellitus are marked by impaired adipose tissue function, contributing to obesityrelated metabolic dysfunction. Adipocyte-derived extracellular vesicles (adEVs) play a crucial role in interorgan crosstalk, influencing metabolism in distant tissues, such as the skeletal muscle. Preclinical studies suggest that adEVs derived from obese adipocytes impair insulin signaling in skeletal muscle. Recent work has identified a novel role of mitochondria in communicating with the endosomal compartment, by the release of mitochondrialderived EVs. Interestingly, pilot data show mitochondrial proteins in adEVs and demonstrated their uptake by in vitro myotubes, suggesting a role in regulating energy conversion and insulin signaling. In this project, we hypothesize that adEVs carry mitochondrial cargo that affects skeletal muscle metabolism and insulin sensitivity. This project aims to investigate how mitochondrial-derived vesicles (MDVs) in adipocytes from donors with or without obesity shape adEVs, and how mimicking exercise in vitro influences their mitochondrial protein signature. These findings could offer novel insights into interorgan crosstalk in metabolic disease states, ultimately advancing therapeutic strategies for obesity and type 2 diabetes mellitus.

01 October 2025 - 30 September 2029