Mixed assemblies (micellar but also lamellar and liquid crystalline phases) made of lipids and bile salts form during digestion, responsible for the transport of lipids and lipophilic micro-constituents such as vitamins A, E, D, K, carotenoids, sterols. But the determinants of their solubilization capacity (amount they can load) are poorly known.
The goal of this project is to understand the role of the fatty acid and monoglyceride type on the structure of the assemblies and on their solubilization capacity for lipophilic micro-constituents, and how these structures influence the absorption of these compounds.
Static structure and solubilization measurements will be complemented by early structuration kinetics monitored by time-resolved synchrotron SAXS, and absorption kinetics through Caco-2 cells and in bile duct-ligated rats. Molecular dynamics will be performed to reveal the organization of the micro-constituents in the assemblies. To validate the mechanistic knowledge gained, an absorption study in normal rats will be performed using emulsions as model lipid foods.
1) Micelle-vesicle structural transition at increasing lipid concentration, except for the caprylic system (only micelle found).
2) Resolution of micelle and vesicle molecular structures in the presence or absence of a lipophilic compound.
3) A solubilization limit in the assemblies was found for vitamins E and K, higher in vesicles compared to micelles.
4) No solubilization limit in the assemblies was found for vitamins A and D, in the wide concentration ranges studied.
The second main part of the project will start in 2020, in C2VN lab for absorption experiments in mice. Assembly simulation using molecular dynamics will also be conducted in 2020, in SayFood lab. SAXS experiments in Synchrotron SOLEIL are planned for late 2020, about assembly formation kinetics.
A manuscript is currently being finalized before submission to an international peer-reviewed journal.
Des assemblages mixtes (micellaires mais aussi lamellaires…) composés de lipides et de sels biliaires se forment pendant la digestion, responsables du transport des lipides et des micro-constituants lipophiles tels que les vitamines A, E, D, K, les caroténoïdes, les stérols. Mais les déterminants de leur capacité de solubilisation (la quantité incorporée) ne sont pas bien connus. L’objectif de ce projet est de comprendre le rôle du type d’acide gras et monoglycéride sur la structure des assemblages et sur leur capacité de solubilisation des micro-constituants lipophiles, et comment ces structures influencent l’absorption de ces composés. Des mesures statiques de structure et de solubilisation seront complémentées par des cinétiques de structuration aux temps courts suivies par SAXS de synchrotron, et des cinétiques d’absorption en Caco-2 et chez le rat avec ligature des voies biliaires. Des simulations de dynamique moléculaire seront réalisées pour révéler l’organisation des micro-constituants dans les assemblages. Pour valider les connaissances mécanistiques acquises, une étude d’absorption chez le rat normal sera réalisée avec des émulsions comme aliments lipidiques modèles.
Monsieur Sebastien Marze (Biopolymères, Interactions Assemblages)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
BIA Biopolymères, Interactions Assemblages
IPR INSTITUT DE PHYSIQUE DE RENNES
GENIAL Ingénierie Procédés Aliments
C2VN Centre recherche en CardioVasculaire et Nutrition
Help of the ANR 228,778 euros
Beginning and duration of the scientific project:
October 2018
- 36 Months