Aerobic exercise training regulates serum extracellular vesicle miRNAs linked to obesity to promote their beneficial effects in mice

There is a growing body of evidence that extracellular vesicles (EVs) and their cargo of RNA, DNA, and protein are released in the circulation with exercise and might mediate interorgan communication. C57BL6/J male mice were subjected to diet-induced obesity and aerobic training on a treadmill for 8 wk. The effect of aerobic training was evaluated in the liver, muscle, kidney, and white/brown adipose tissue. To provide new mechanistic insight, we profiled miRNA from serum EVs of obese and obese trained mice. We demonstrate that aerobic training changes the circulating EV miRNA profile of obese mice, including decreases in miR-122, miR-192, and miR-22 levels. Circulating miRNA levels were associated with miRNA levels in mouse liver white adipose tissue (WAT). In WAT, aerobically trained obese mice showed reduced adipocyte hypertrophy and increased the number of smaller adipocytes and the expression of Cebpa, Pparg, Fabp4 (adipogenesis markers), and ATP-citrate lyase enzyme activity. Importantly, miR-22 levels negatively correlated with the expression of adipogenesis and insulin sensitivity markers. In the liver, aerobic training reverted obesity-induced steatohepatitis, and steatosis score and Pparg expression were negatively correlated with miR-122 levels. The prometabolic effects of aerobic exercise in obesity possibly involve EV nuRN As, which might be involved in communication between liver and WAT. Our data provide significant evidence demonstrating that aerobic training exercise-induced EVs mediate the effect of exercise on adipose tissue metabolism.