Exercise protects against obesity-induced endothelial dysfunction via promoting perivascular adipose tissue browning

Abstract

Overweight and obesity have reached epidemics worldwide. Obesity represents the independent risk factor for a serious of diseases including cardiovascular diseases. Exercise is one of the most efficient ways to prevent or delay the onset of cardiovascular diseases. But the detailed mechanism is still poorly understood. Perivascular adipose tissue (PVAT) is the adipose tissue surrounding the blood vessels. Emerging evidence has shown that PVAT plays an active role in modulating vascular functions and displays multiple characteristics of brown adipose tissue (BAT). Uncoupling protein-1 (UCP1) resides on the mitochondria inner membrane and serves to dissipate energy in form of heat. In the current project, we aim to elucidate the effects of moderate exercise on endothelial function and examined the role of PVAT and UCP1 within PVAT during this event. By using Ucp1 knockout (Ucp1 KO) mice, we firstly characterized the basic features of the mice and the adipose tissues. Morphological analysis indicated that PVAT exhibited morphology typical of BAT while Ucp1 deficient PVAT had enlarged lipid droplet within it. After one month of high fat diet feeding, both the obese WT and Ucp1 KO mice were subjected to daily exercise training and the metabolic benefits of the moderate exercise were evaluated. The results demonstrated that exercise improved glucose tolerance in both WT and Ucp1 KO mice. However, wire myograph analysis revealed that although exercise was efficacious to alleviate obesity-evoked endothelial dysfunction, such an effect was largely abolished in Ucp1 deleted mice. Therefore, we demonstrated that exercise-elicited protection against endothelial dysregulation was dependent on the presence of UCP1 within PVAT. The current study provides new insights into novel strategies to prevent/cure cardiovascular diseases.