Extracellular vesicles and microRNAs are altered in response to exercise, insulin sensitivity and overweight

Abstract

Extracellular vesicles induced by exercise have emerged as potential mediators of tissue crosstalk. Extracellular vesicles and their cargo miRNAs have been linked to dysglycemia and obesity in animal models, but their role in humans is unclear. Aim:The aim of the study was to characterize the miRNA content in plasma extracellular vesicle isolates after acute and long-term exercise and to study associations between extracellular vesicle miRNAs, mRNA expression in skeletal muscle and adipose tissue, and cardiometabolic risk factors.Methods: Sedentary men with or without dysglycemia and overweight underwent an acute bicycle test and a 12-week exercise intervention with extensive metabolic phenotyping. Gene expression in m. vastus lateralis and subcutaneous adipose tissue was measured with RNA sequencing. Extracellular vesicles were purified from plasma with membrane affinity columns or size exclusion chromatography.Results: Extracellular vesicle miRNA profiling revealed a transient increase in the number of miRNAs after acute exercise. We identified miRNAs, such as miR-652-3p, that were associated to insulin sensitivity and adiposity. By performing explorative association analyses, we identified two miRNAs, miR-32-5p and miR-339-3p, that were strongly correlated to an adipose tissue macrophage signature. Conclusion:Numerous miRNAs in plasma extracellular vesicle isolates were increased by exercise, and several miRNAs correlated to insulin sensitivity and adiposity. Our findings warrant future studies to characterize exercise-induced extracellular vesicles and cargo miRNA to clarify where exercise-induced extracellular vesicles originate from, and to determine whether they influence metabolic health or exercise adaptation.

Distinct microRNA and protein profiles of extracellular vesicles secreted from myotubes from morbidly obese donors with type 2 diabetes in response to electrical pulse stimulation

“…The finding that EPS increases miR-320b might therefore be noteworthy. Several studies on exercise and plasma EVs have been reported ( Estebanez et al, 2021 ; Doncheva et al, 2022 ). The review by Estebanez et al summarized results of released exosome miRs in plasma after four different exercise protocols ( Estebanez et al, 2021 ).…”

“…In this latter study, they additionally revealed that exercise evoked EVs could transfer their protein content into the liver, implying a role in tissue crosstalk during exercise. Also, the level of miRs in plasma EVs increased by exercise in a group of sedentary men ( Doncheva et al, 2022 ). However, the origin of plasma EV is manifold, and the contribution of skeletal muscle EVs is unknown, although, it has been suggested that about 5% of plasma EVs are derived from skeletal muscles ( Estrada et al, 2022 ).…”

Hormones—Modulators of metabolism

“…Acute exercise can increase several miRNAs (including miR-652-3p) in extracellular vesicles, which were associated with insulin sensitivity and adiposity. 10 Type 2 diabetes is characterized by insulin resistance coupled with insufficient glucose uptake by muscle and fat and unrestricted hepatic glucose production. This results in hyperglycemia.…”

“…Extracellular vesicles can function as components in cell–cell and tissue‐tissue communication and they are implicated in immune responses and insulin resistance. Acute exercise can increase several miRNAs (including miR‐652‐3p) in extracellular vesicles, which were associated with insulin sensitivity and adiposity 10 …”

The rise and fall of circulating miRNAs in response to exercise

“…In this issue of Acta Physiologica , Doncheva et al 1 advance our understanding of biomarkers that reflect tissue‐specific cardiometabolic disease. They did so by measuring circulating miRNAs within extracellular vesicles (EVs) regulated by exercise in human plasma and defining their associations with the transcriptome of metabolically active tissues during obesity.…”