Deciphering the intestinal absorption pathways of fat-soluble vitamins using unbiased approaches based on functional vitamin probes and proteomics – AbSoluTe

The ambition of the project AbSoluTe is to decipher how fat-soluble vitamins D and E (FSV) enter and traffic across the enterocyte.
FSV are small lipids essential to sustain life. Intense research is dedicated to increasing their absorption to tackle deficiencies. However, this research is considerably limited by our partial knowledge of FSV intestinal absorption pathways.
Lipid transporters involved in FSV intestinal absorption have been identified using targeted approaches, but these approaches are limited. No functional tools are available to visualize FSV transport across the enterocytes and FSV partner proteins still remain to be identified.
The project aims at deciphering FSV absorption process through the intestinal cell by following 3 objectives:
- DESIGN: we will design and synthetize functional FSV probes,
- VIZUALIZE: we will use FSV probes to visualize FSV transport across the enterocyte at the subcellular level,
- IDENTIFY: we will use FSV probes and proteomics to identify FSV partner proteins in an unbiased manner.
To this aim, we will implement a combination of in vitro and in vivo techniques from microscopy to thermal proteome profiling.
This project will allow us to understand whether FSV absorption is driven by lipid fluxes and/or whether unidentified proteins are involved in their transport.
This project will provide data relevant for i) other lipids/ lipophilic drugs absorbed by the enterocytes and ii) other cell types metabolizing FSV. The developed functional FSV probes will be of major interest in all aspects of nutritional sciences dealing with FSV metabolism and health effects.
The findings from this study will support research aiming at improving FSV bioavailability and will constitute a strong knowledge base for the establishment of tailored recommendations, which can have far-reaching consequences in human nutrition, and thereby also public health.