PostEVs

Contact : Laurent-Emmanuel Monfoulet

Abstract

Postprandial nutritional stress is known to cause transient metabolic disturbances whose long-term recurrence contributes to the development of cardiometabolic diseases. Among the physiological changes occurring in the postprandial period, the secretion of extracellular vesicles (EVs) is poorly documented. These nanostructures composed of cell membranes are, however, attracting growing interest due to variations in their circulating levels in situations of physiological stress and during the onset of cardiometabolic disorders. These structures are actors in intercellular communication by propagating biological messages consisting of lipid mediators, protein signals and nucleic acid molecules. The factors modulating the secretion of EVs as well as the biological consequences associated with these structures are still very 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 rise in EV levels during 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 component of our diet can favorably impact the biology of postprandial EVs, particularly in response to nutritional stress. To address this, the first objective is to characterize in detail the EVs secreted (populations and content) following pro-oxidant and pro-inflammatory postprandial stress and to determine the constituents that can specifically identify postprandial EVs. The project also aims to determine the biological role of postprandial EVs, particularly on certain cardiometabolic functions. Based on the knowledge thus generated, Post’EVs will be able to evaluate the capacity of certain bioactive plant microconstituents in food (from the polyphenol family) to modulate the secretion, content and biological functions of postprandial EVs in humans.

To achieve these objectives, the project will draw on human samples from an ongoing randomized, controlled nutritional intervention study. For the first time, it will combine cutting-edge EV identification technology with multidimensional, non-targeted analysis of EV constituents to provide a comprehensive and highly detailed characterization of postprandial EV populations and their content. It will determine the bioactivity of postprandial EVs on various cardiometabolic functions through ex vivo assessments. Finally, proof of concept that polyphenols can modulate postprandial EVs will be provided for hesperidin, the major polyphenol in oranges, which has been shown in numerous studies to contribute to the health effects of oranges. The Post’EVs project is a prerequisite for understanding the role of postprandial EVs in the effects of our diet, and particularly the polyphenol component of plant products, on our physiology and health. Overall, the project will shed new light on the postprandial response and its essential role in the development of cardiometabolic disorders. Beyond knowledge in nutritional biology, this project will provide extensive data on the characterization of EVs, which are necessary for the development of EVs as reliable health biomarkers.

Parteners

PHYMEDEXP Physiologie et médecine expérimentale du coeur et des muscles ; CICS Centre Imagerie Cellulaire Santé