Deciphering the Role of Dietary Fatty Acids on Extracellular Vesicles-mediated Intercellular Communication and Their Implication in Atherosclerosis and Metabolic Syndrome: a Multi-omics Approach to Precision Nutrition

Dietary interventions have been consistently proposed as a part of a comprehensive strategy to lower the incidence and severity of atherosclerosis and coronary vascular disease. Excessive comsumption of fats enriched in saturated fatty acids (SFAs) is associated with an increased risk of atherosclerosis and other cardiovascular diseases (CVD). In contrasts, replacement of SFAs with monounsaturated fatty acids (MUFAs) and omega-3 long chain polyunsaturated fatty acids (ω3-LCPUFAs) has been reported to be inversely associated with risk of atherosclerosis. This is partly due to the ability of MUFAs (and ω3-LCPUFAs) to modulate lipoprotein composition, oxidation state, and consequently their functionality, among others. While most of the nutritional studies have focused on elucidating the mechanisms by which dietary fats affect lipoprotein particles, little or nothing is known about the regulatory effect of dietary fatty acids on extracellular vesicles (EVs). EVs are small phospholipid particles that convey molecular bioactive cargoes and play essential roles in intercellular communication and, hence, a multifaceted role in health and disease. For the first time, the purpose of this project is to establish whether the type of major fatty acids present on a diet (SFAs, MUFAs, or ω3-LCPUFAs) may alter the structure, cargo, and functionality of postprandial- and long-term-EVs. In the precision nutrition era, the investigators expect to offer a new insight on EVs and their relationship with dietary fatty acids through the following objectives: 1) To map changes in the lipidome, proteome, microtranscriptome, and functional properties of circulating EVs in healthy subjects and patients with metabolic syndrome (MetS) both at fasting and at postprandial state upon a challenge of a meal rich in SFAs, MUFAs, and ω3-LCPUFAs; 2) To analyse the contribution of postprandial triacylglyceride-rich lipoproteins (TRL) on EVs-mediated intercellular communication in a fatty acid-dependent manner; and 3) To determine the influence of diets rich in SFAs, MUFAs, and ω3-LCPUFAs on EVs in an animal model of atherosclerosis in the setting of MetS. Collectively, this project will provide fundamental insight into EV biology, and remarks the clinical and functional relevance and divergent consequences of dietary fatty acids in health and disease.