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Last update: May 2021

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Oxygenate

The Project

Project overview

The OXYGENATE project aims to uncover and validate the oxylipin signatures reflecting the cardiometabolic status or its early transition towards the CardMetS.

Our strategic objective is to identify and validate candidate oxylipins (i) differentiating individuals at different stages of CardMetS and individuals with different quality of dietary patterns and (ii) evolving consistently with dietary interventions affecting the cardiometabolic endpoints.

Three measurable and technological objectives have been identified :

1. To optimize the targeted lipidomic profiling of oxylipins by (i) enlarging the current oxylipin profile, (ii) determining the optimized conditions for storage and preparation, (iii) performing method transfer and inter-lab validation and (iv) performing tests of automatization for the rate-limiting steps.

2. To identify, in a first cohort (PURE), the candidate oxylipins reflecting cardiometabolic transition and its relationships with diet by measuring the comprehensive profile of oxylipins in individuals (i) with different dietary patterns and (ii) with or without CardMetS (cross-sectional analyses) as well as (iii) before and after the development of CardMetS (longitudinal analyses).

3. To validate the reliability and consistency of the candidate oxylipins identified (i) by replicating the cross-sectional analyses in an independent cohort (NutriNet-Santé) and (ii) by monitoring the changes in the candidate oxylipins in response to whole diet intervention using existing biobanks from 2 intervention studies performed in individuals with altered cardiometabolic status.

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WP1: METHOD OPTIMIZATION

WP1 aims to provide an optimized and reliable method for the quantitative profiling of plasma oxylipins.

Our strategic objective is to optimize the established method developed by Dr N Schebb by (i) enlarging the current oxylipin profile, (ii) performing tests of automatization for the rate-limiting steps, (iii) optimizing conditions of storage and preparation, (iv) performing method transfer and inter-lab validation. WP1 will be performed using different pooled plasma samples constituted by Dr N Schebb from existing biobanks or from commercial stocks.

WP1 will be led by Univ. Hannover (Leader of WP, involved in method development, training and transfer, data collection and analysis), and will involve USDA Davis (Consultant for method development, involved in inter-lab validation), INRA/UNH (Inter-lab validation and setting up of the automatization tests on robots with recruited PhD student). This WP will also include 2 subcontractors (Lipidomix, DE and MetaToul Lipidomic Platform) who will be involved in the inter-lab validation.

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WP2: DISCOVERY

WP2 aims to identify candidate oxylipins discriminating (i) the dietary patterns and (ii) the cardiometabolic status and (iii) predictive of CardMetS development.

Our strategic objectives are to perform (1) cross-sectional analysis aiming to compare the oxylipins profiles of individuals with different quality of dietary patterns and with or without CardMetS and (2) longitudinal analysis aiming to compare individuals at different stages of CardMetS development. The identification of the candidate oxylipins will be performed following a succession of steps including: (i) identification of candidate oxylipins using discriminant modelling, (ii) characterization of the candidate oxylipins including correlation with dietary and clinical parameters and assessment of their biological plausibility and (iii) assessment of the prediction performance of the candidate oxylipins identified

WP2 will be conducted in a collaborative effort between Univ. Wroclaw (co-leader of WP, in charge of PURE subjects selection, plasma samples expedition, dietary score computation, metabolic syndrome assessment and data analyses and interpretation) and INRA/UNH (co-leader of WP, in charge of biostatistics/data analysis and interpretation) and will involve USDA Davis (assistance in biostatistics, data analysis and interpretation), Univ. Hannover (oxylipin profiling) and INSERM/EREN (assistance in biostatistics, data interpretation) and NEXS/UCPH (data management and sharing).

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WP3: VALIDATION

WP3 aims to validate the consistency of the candidate oxylipins identified in WP2 and assess their reliability and convenience to monitor the efficacy of a dietary intervention.

Three specific objectives have been identified (i) To replicate the cross-sectional analyses in an independent cohort allowing to validate the consistency and the reproducibility of the candidate oxylipins identified in WP2, (ii) To assess the reliability of the candidate oxylipins to monitor the changes of CardMetS status in response to dietary intervention and (iii) To conceptualize visualization tools to simplify the interpretation of the candidate oxylipins identified and validated.

WP3 will be led by INSERM/EREN (in charge of subjects selection in the NutriNet-Santé cohort, plasma samples expedition ; dietary score computation and metabolic syndrome assessment for NutriNet-Santé subjects, contribution to data analyses and interpretation) and will involve INRA/UNH (oxylipin profiling, in charge of data analysis and interpretation), USDA Davis (oxylipin profiling of the iMAPS samples, contribution to data analyses and interpretation) and NEXS/UCPH (data management and sharing, provide samples from the SHOPUS study and assistance in data analyses and interpretation).