Extracellular Vesicles and Circulating miRNAs—Exercise-Induced Mitigation of Obesity and Associated Metabolic Diseases

Abstract

Obesity is a progressive chronic disease that is defined by increased adiposity and dysregulated blood lipid and glucose profiles. This, coupled with insulin resistance and hypertension, leads to the development of the metabolic syndrome in obese patients. Furthermore, obesity correlates strongly with an elevated risk and progression of a number of different cancers. Endurance exercise is a gold standard method for rescuing obesity and the associated metabolic dysfunction. Physical activity stimulates fat loss, evokes metabolic adaptations and induces browning of white adipose tissue. The ‘brown’ fat depots are thermogenically active, thereby facilitating energy expenditure and weight loss. New evidence suggests that the systemic effects of exercise are mediated by extracellular vesicles (EVs). These are released from all cell types, and contain canonical myokines that are shed from skeletal muscle, as well as a plethora of other molecular cargo including miRNA, mRNA, DNA, metabolites and proteins. Pro-metabolic myokines include proteins, as well as miRNAs that are linked to rescuing obesity and associated metabolic syndrome. Circulating miRNAs have been shown to be useful biomarkers of pathological conditions including obesity, cancer and the metabolic syndrome. EVs and their enclosed molecular cargo offers a viable therapeutic target for future studies designed to mimic exercise and recapitulate the beneficial effects of exercise in obese subjects.