Final Report Summary - ENDOMED (Characterizing the effects of the Mediterranean diet on endothelial dysfunction) Postprandial metabolism raises as a main factor for developing inflammation related diseases. Glucose homeostasis, thrombosis or fibrinolysis balance and lipoprotein metabolism are features of the postprandial metabolism that can be changed by the type of diet, and particularly by the type of consumed fat. It was recently discovered by our group that dietary fat could even influence gene expression in Peripheral blood mononuclear cells (PBMCs), inducing different gene expression profiles depending on the type of consumed fat. These gene expression changes were the result of the combination of the direct and indirect effects of the fatty acids on the PBMCs, the different tissues and organs that released several hormones and cytokines as a response to the impact induced by the consumed fat. Whether these gene expression changes are in fact translated to protein is not known yet; however previous studies pointed to an increased adhesion capacity to the endothelial cells after the consumption of a high fat meal, therefore promoting intravascular infiltration of the PBMCs. Following these preliminary results we considered that pathways of the transcription factors NF-?B and PPARa, plus the Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, might be differently up-regulated by the distinct types of dietary fat. IL1B is a potent pro-inflammatory cytokine that is secreted by macrophages in the adipose tissue of type-II diabetic patients and its transcription is regulated by the nuclear transcription factor ?B (NF-?B) activity. Moreover, PDK4 is a known PPARa target gene and NCF4 is a cytosolic regulatory member of the NADPH oxidase complex, which is responsible of the production of superoxide anion within the cells. The up-regulation of these genes suggested that Polyunsaturated fatty acids (PUFA) and Mono-unsaturated fatty acid (MUFA) might be able to induce a postprandial pro-inflammatory response prior to an increase in Reactive oxygen species (ROS) production. Moreover, in response to the fat intake, the Peroxisome proliferator-activated receptor alpha (PPARa) was up-regulated as well and proved to be sensible to polyunsaturated and monounsaturated fatty acids. Along the course of the ENDOMED project we also examined whether these pathways were fully activated during in vivo monocytes from lean healthy and obese healthy subjects via the measurement of other genes related to inflammation, lipid metabolism and oxidative stress pathways. These studies were anticipated to reveal whether distinct dietary fats induced different gene expression changes, thus providing some information for future nutritional advice and for reducing the development of inflammation related diseases, such as type-II diabetes or cardiovascular diseases. Related documents Final Report - ENDOMED (Characterizing the effects of the Mediterranean diet on endothelial dysfunction)
