Effects of a high saturated fat diet on inflammatory response in aortic endothelium of TLR-4 (-/-) mice supplemented with omega-3 and omega-6 fatty acids

Abstract

High fat diet is associated with insulin resistance and endothelial dysfunction, but the effects of n-3 and n-6 FA on inflammatory processes and its association with insulin resistance still remain to be clarified. The aim of this study is to investigate the effect of n-3 (fish oil) and n-6 (soybean oil) FA supplementation on the inflammatory process, insulin resistance and endothelial dysfunction induced by high saturated fat diet and the involvement of TLR-receptor 4 in these conditions. We will examine the vascular endothelium of the aorta from C3H/HeJ and TLR-4 (-/-) knockout mice. The supplementation with n-3 or n-6 FA will initiate in the first week and will extend until to the end of the experimental protocol (week 12). Up to the fourth week of FA supplementation, the animals will receive a balanced diet. After this period, animals will continue in a balanced diet or will be subjected to high saturated fat diet for 8 weeks (from weeks 5 to 12). The following parameters will be measured: insulin sensitivity, endothelial activation markers (ICAM-1, VCAM-1, E-selectina, P-selectina, MCP-1 and eNOS), mediators of inflammation (IL-6, TNF-alfa, IL-1 beta, IL-10 and C-reactive protein, TLR-4 protein and signaling proteins (MyD88, IRAK1 and NFºB) and MAPKinases signaling (JNK and p38). A better understanding of the mechanisms involved in the FA action have direct impact on the elucidation of the issues related to obesity and endothelial dysfunction as well as in developing new therapies that target intracellular pathways involved in inflammation.