PostEVs

Postprandial nutritional stress is known to be the cause of transient metabolic disturbances whose long-term recurrence contributes to the development of cardiometabolic diseases. Among the physiological changes occurring after a meal, the postprandial secretion of extracellular vesicles (EVs) is poorly documented. However, these nanostructures composed of cell membranes are of increasing interest because of the variations in their circulating levels in physiological stress situations and in the onset of cardiometabolic disorders. These structures sustain a cell-to-cell communication because of their content which confers them the capacity to propagate biological messages made up of lipid mediators, protein signals and nucleic acid molecules. The factors that modulate EV secretion and the biological consequences associated with these structures are still poorly understood. However, nutritional approaches based on plant foods rich in microconstituents such as polyphenols, known for their health benefits, have been shown to reduce the elevation of EV level in cardiometabolic disorders. However, the daily impact of our diet and these plant microconstituents on the secretion of postprandial EVs and their biological activities is not known. The Post'EVs project hypothesizes that the polyphenols provided by the plant food may favorably impact the biology of postprandial EVs, particularly in response to nutritional stress. To answer this question, the first objective is to characterize accurately the secreted EVs (population and content) following a pro-oxidative and pro-inflammatory postprandial stress and to determine the constituents allowing to identify specifically postprandial EVs. The project also aims to determine the biological role(s) of postprandial EVs, particularly on cardiometabolic functions. Post’EVs will also evaluate the capacity of certain bioactive plant microconstituents (mainly polyphenol) to modulate the secretion, content and biological functions of postprandial EVs in humans. To meet these objectives, the project will use human samples from an ongoing randomized controlled nutritional intervention study. It will combine for the first time an innovative EV identification technology with a multi-dimensional and untargeted analysis of EV constituents to provide the most comprehensive characterization of postprandial EV populations and their contents. It will determine the bioactivity of postprandial EVs on different cardiometabolic functions through ex vivo assessments. Finally, the proof of concept that polyphenols can modulate postprandial VEs will be done for hesperidin, the main polyphenol of the orange, which represents one of the 3 most consumed citrus fruits in the world and for which numerous studies show beneficial effects for health in connection with its polyphenol content. The achievement of the Post'EVs project is a need for understanding the role of postprandial EVs in the effects of our diet, and especially the polyphenol component , on our physiology and our health. As a whole, the project will shed new light on the postprandial response and its primary role in the development of cardiometabolic disorders. Beyond the knowledge in nutritional biology, this project will provide useful data on the characterization of EVs necessary in a perspective of the development of EVs as reliable biomarkers in health.