Long-term exercise-secreted extracellular vesicles promote browning of white adipocytes by suppressing miR-191a-5p.

The purpose of the study is to explore the mechanism of transdifferentiation from white adipose tissue (WAT) to Brown adipose tissue (BAT). In this study, we established a model of mouse obesity induced by a high-fat diet (HFD) before 30 days of forced exercise or sedentary mice. Then, we isolated extracellular vesicles (EVs) from plasma and identified them by transmission electron microscope, dynamic light scattering and western blot analysis. Body temperature and body weight were utilized for assessment of thermogenesis in vivo. Oil red O staining was used to measure triglyceride in vitro. Luciferase reporter assay was applied for the relationship between miR-191a-5p and Prdm16. As a result, mice that exercised for a long period time exhibited higher caloric expenditure, better weight maintenance and more WAT browning, as well as better resistance to obesity associated with a high-fat diet, compared to mice that lacked exercise. MircoRNA-191-5p (miR-191-5p) was found to be lowly expressed in the EVs from mice with long-term exercise (Exe-EVs). Functional experiments revealed that Exe-EVs promoted WAT browning by the silencing of miR-191-5p. At the molecular level, siRNA-mediated PRDM16 partly inhibited uncoupling protein-1(UCP-1) expression by miR-191-5p inhibitor in white adipocytes. Here, we observed that the lowly expressed miR-191-5p in Exe-EVs promoted the browning of WAT by negatively targeting the PRDM16-3'-untranslated region (PRDM16-3'UTR), thereby enhancing heat production and reducing obesity. MiR-191-5p may serve as a potential target for the identification and treatment of obesity.