Question: 

Endothelial dysfunction is an early step in the pathogenesis of atherosclerosis. A high-fat diet has been associated with an increased risk of endothelial dysfunction and atherosclerosis. Therefore, we investigated the impact of high-fat diet on endothelial function.

Methods and results: 

C57BL/6J mice were fed a high-fat diet containing 60 kcal% fat for 20 weeks. During feeding period mice on high-fat diet gained significantly more weight than mice on standard rodent chow. Interestingly, the cumulative food intake was lower in mice on high-fat diet compared to the control group. The mice on high-fat diet revealed differences in serum parameters compared to mice on standard chow. We detected increased blood glucose, triglyceride, total cholesterol, and low-density lipoprotein levels. Using Mulvany myograph, we characterized vascular function in the aorta of these mice. We could show an altered endothelium-dependent vasorelaxation by acetylcholine concentration response curves in mice on high-fat diet. This difference was partially reduced by COX-1/2 inhibitor diclofenac. Interestingly, catalase leads also to a different pattern of vasorelaxation. In addition, mice on high-fat diet showed a decrease in contractility as indicated by lower phenylephrine concentration response curves. Endothelium-independent vasorelaxation was tested by sodium nitroprusside and showed in all experimental set-ups no differences.

Conclusion: 

We established an obesity model in C57BL/6J mice. High-fat diet induced endothelial dysfunction in these mice. Hydrogen peroxide and prostaglandins might be involved in the development of severe endothelial dysfunction.