Project R-13425

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

In obesity, body fat distribution is a strong cardiometabolic risk factor, being associated with obesity-related comorbidities and all-cause mortality. Moreover, sexual dimorphism in adipose tissue (AT) distribution partly explains gender differences in tissue-specific insulin sensitivity, which may result from ectopic lipid deposition in metabolic organs. Besides an impaired AT function, interorgan crosstalk is often disturbed in the obese insulin-resistant state. Within this field, the study of AT derived secretory extracellular vesicles (adEVs), which are submicron-sized membranous biological vesicles involved in the transport of a wide range of disease-specific biomarkers through biological fluids, is novel. However, sexual dimorphism in terms of adEVs, their association with depotspecificity, as well as their role in skeletal muscle insulin resistance need to be characterized in more detail. The aim of this translational project is to investigate the role of human depot-specific adEVs in skeletal muscle insulin resistance and their association with gender. Gaining mechanistic insights into the role of depot- and/or genderspecific adEVs in inducing skeletal muscle-specific insulin resistance will help to explain metabolic heterogeneity among obese individuals and may identify novel targets for prevention and treatment strategies of obesity, possibly including more personalized, EV-based exercise interventions.

01 November 2022 - 31 October 2026