Perivascular adipose tissue (PVAT), a type of adipose tissue which surrounds blood vessels, has been considered as an active component of blood vessel walls and involved in vascular homeostasis. Recent evidence shows that increased inflammation and oxidative stress in PVAT contribute to endothelial dysfunction in type 2 diabetes (T2D). Exercise is an important non-pharmacological approach for vascular diseases. However, there is limited information regarding whether the beneficial effects of exercise on vascular function is related to PVAT status. In this study, we investigated whether exercise can decrease oxidative stress and inflammation of PVAT and promote the improvement of endothelial function in a T2D mouse model. Diabetic db/db (5-wk old) mice performed treadmill exercise (10 m/min) or keep sedentary for 8 wks. Body weight, fasting blood glucose levels, glucose and insulin tolerance were determined. The cytokines (IL-6, IL-10, IFN-r, TNF-a) and adiponectin levels, macrophage polarization in PVAT, and oxidative stress and nitric oxide expression in vascular wall were evaluated. The leukocyte adhesion ability of aorta endothelial cells isolated from the db/db mice was analyzed. Our data showed that: 1) Exercise decreased body weight and the fasting blood glucose level as well as improved glucose tolerance and insulin sensitivity in T2D mice. 2) Exercise increased adiponectin and IL-10 levels, decreased IFN-r, IL-6, TNF-a levels and promoted M1 to M2 polarization in PVAT. 3) Exercise decreased superoxide production in the vascular wall of diabetic mice, accompanied with increased nitric oxide bioavailability. 4) Exercise decreased the adhesion of diabetic aorta endothelial cells to leukocytes, accompanying with decreased ICAM-1 and VCAM-1 expression.
In conclusion, our data suggest that exercise improved endothelial function by attenuating the oxidative stress and inflammation in PVAT.
J. Wang: None. V. Polaki: None. S. Chen: None. J. Bihl: None.
American Diabetes Association (1-17-IBS-187 to J.B.)