Voluntary Exercise Ameliorates the Progression of Atherosclerotic Lesion Formation via Anti-Inflammatory Effects in Apolipoprotein E-Deficient Mice

Aim: A sedentary lifestyle with insufficient exercise is associated with cardiovascular disease. Previous studies have demonstrated that endurance exercise benefits atherosclerosis and cardiovascular disorders; however, the mechanisms by which physical activity, such as voluntary exercise (Ex), produces these effects are not fully understood. Methods and Results: Eight-week-old male apolipoprotein (ApoE)-deficient mice were fed a standard diet (STD) or high fat diet (HFD) for 10 weeks. The HFD+ Ex group mice performed Ex on a running wheel for 10 weeks. No significant differences in lipid profiles were observed between the HFD and HFD+ Ex groups. Although changes in body and brown adipose tissue weights were comparable between the HFD and HFD+ Ex groups, white adipose tissue weight was significantly lower in the HFD+ Ex group than in the HFD group. The areas of atherosclerotic lesions in the aortic sinus and thoracoabdominal aorta were significantly reduced in the HFD+ Ex group than in the HFD group (p< 0.001). There was a strong negative correlation between atherosclerotic areas and the mean running distance per day in the HFD+ Ex group (r =-0.90, p = 0.01). Endothelial function was significantly preserved in the HFD+ Ex group (p< 0.05). Serum interleukin-6 and macrophage chemoattractant protein-1 levels were significantly lower and those of adiponectin were significantly higher in the HFD+ Ex group than in the HFD group (p< 0.05). Conclusions: These results suggest that Ex ameliorates the progression of endothelial dysfunction and atherosclerotic lesion formation through anti-inflammatory effects, despite continued consumption of HFD.