Oxylipins signature to monitor the cardiometabolic status and its response to dietary intervention

ERA-HDHL cofunded call “Biomarkers for Nutrition and Health” (BioNH 2016)
Oxylipins signature to monitor the cardiometabolic status and its response to dietary intervention
OXYGENATE
2017-06-01
2021-08-31
GLADINE
Institut National de la Recherche Agronomique
France

Consortium

Partner Organization Partner Country
Centre de Recherche en ÉpidémiologiesFrance
University of CopenhagenDenmark
University of WuppertalGermany
Wroclaw Medical UniversityPoland
USDA/UC DavisUSA

1. Overall project description


1.1 Summary

Rational & Objectives. There is an urgent need to find reliable early biomarkers of the cardiometabolic syndrome (CardMetS) allowing intervention before irreversible damage develops while assessing the efficacy of nutritional prevention. Oxylipins could be relevant candidate biomarkers thanks to their involvement in the homeostatic regulation of various process related to the cardiometabolic status and the consistent link reported between diet, oxylipins and cardiometabolic dysregulations. Moreover, the oxylipin profiling could provide a mechanistic signature at the metabolite level allowing a better stratification of patients at risk of cardiometabolic diseases (CVD and diabetes).


Our main objective in the OXYGENATE project was to uncover and validate the oxylipin signatures reflecting the cardiometabolic status or its early transition towards the CardMetS. To achieve this goal, we proposed a multidisciplinary project involving experts in lipidomics, nutrition and epidemiology and combining the comprehensive and quantitative lipidomic profiling of circulating oxylipins and the use of different biobanks from large prospective cohorts and different whole-diet interventions.


Overall achievements. The OXYGENATE project started with the optimization of the MS-based targeted lipidomic profiling of oxylipins. The optimized method developed allows a comprehensive profiling of all types of oxylipins including the free and the esterified forms. The method has been validated through a round robin test involving 5 different laboratories worldwide and allowing to determine for each oxylipin (i) intra- and inter-day variabilities and (ii) consensus values and their respective dispersion. The OXYGENATE consortium also provided a detailed SOP for sample storage and preparation including quantitative and qualitative data regarding oxylipin stability. Using this original method, we have generated the oxylipin profiles of over 1000 participants involved in various independent studies (cross-sectional and longitudinal observational studies and intervention studies) performed in four different populations (Polish, French, Danish and American). So far, the cross-sectional studies nested in the Polish branch of the PURE cohort and the French Nutrinet-Santé cohort lead to the identification of a signature of 23 oxylipins coined OxyScore. This score is highly discriminant of CardMetS and has high performances of classification and replicability. Moreover, the identified oxylipins provide a unique mechanistic signature of MetS that may enhance the prediction of cardiometabolic diseases risk. Complementary cross-sectional studies nested in the same cohorts have been performed to investigate the links between the OxyScore and diet. Moreover, to further validate the OxyScore, we have tested its ability to monitor the changes of cardiometabolic health in response to diet using the biocollection collected in two independent studies (the Danish SHOPUS study and the American iMAPS study).


Expected impacts. On completion, the OXYGENATE project has (i) provided an internationally validated method of comprehensive oxylipins profiling (ii) generated the 1st large diet- and health-related oxylipins database, (iii) identified and validated the oxylipins reflecting the cardiometabolic status and the quality of dietary patterns (biostatistics under progress) (iv) provided a proof-of-concept of the ability of oxylipins to monitor the effect of diet on the cardiometabolic status (biostatistics under progress). It is expected that the oxylipins identified and validated will allow a better detection and management of the cardiometabolic diseases.


1.2 Highlights

In the framework of the JPI-Oxygenate project we have:



  1.          Standardized and validated a MS-based method for the quantitative analysis of over 130 oxylipins including all species found in the free form and esterified into complex circulating lipids.

  2.           Showed that total plasma oxylipins (sum of free and esterified) are stable regarding delays during plasma generation and long-term storage at −80°C.

  3.         Showed that our MS-based method for the quantitative analysis of total oxylipins in plasma has a low technical variability and allow reliable, reproducible and comparable oxylipin concentrations in independent laboratories.

  4.           Identified an oxylipin signature of cardiometabolic syndrome having high performances of classification and replicability.

  5.         Showed that the oxylipin signature of cardiometabolic syndrome provides a unique mechanistic phenotyping informing on crucial molecular pathways that may help identify patients at high risk of cardiometabolic diseases.


4. Impact


4.1 List of publications

AuthorsTitleYear, Issue, PPPartners NumberDoiPdf
Cécile Gladine*, Annika I. Ostermann*, John W. Newman*, Nils Helge Schebb*MS-based targeted metabolomics of eicosanoids and other oxylipins: Analytical and inter-individual variabilities2019, vol 144, 72-893https://doi.org/10.1016/j.freeradbiomed.2019.05.012Download
Elisabeth Koch*, Malwina Mainka*, Céline Dalle*, Annika I. Ostermann*, Katharina M. Rund*, Laura Kutzner*, Laura-Fabienne Froehlich*, Justine Bertrand-Michel*, Cécile Gladine*, Nils Helge Schebb*Stability of oxylipins during plasma generation and long-term storage2020, vol 2173https://doi.org/10.1016/j.talanta.2020.121074Download
Malwina Mainka*, Céline Dalle*, Mélanie Pétéra*, Jessica Dalloux-Chioccioli*, Nadja Kampschulte*, Annika I. Ostermann*, Michael Rothe*, Justine Bertrand-Michel*, John W. Newman*, Cécile Gladine*, and Nils Helge Schebb*Harmonized procedures lead to comparable quantification of total oxylipins across laboratories61(11) 1424–14365https://doi.org/10.1194/jlr.RA120000991Download
Cécile Gladine* and Maria FedorovaThe clinical translation of eicosanoids and other oxylipins, although challenging, should be actively pursued2021, 21, 27-301https://doi.org/10.1016/j.jmsacl.2021.08.003Download

4.2 Presentation of the project

Target groupAuthorsMeans of communicationHyperlinkPdf
Scientists, PhD students and studentsE. Koch, A. I. Ostermann, M. Mainka, C. Dalle, T. Konrad, C. Gladine, N. H. Schebb, Quantification of Total Oxylipins in Plasma – Challenges & Strategies for Hydrolysis and Solid Phase Extraction. 47th International Conference on Food Chemistry and Technology, Berlin, Germany, 2018.Poster
Scientists, PhD students and studentsE Koch, AI. Ostermann, M Mainka, C Dalle, T Konrad, C Gladine, NH Schebb, Extraction of lipids and oxylipins from plasma for quantification of total oxylipins – Challenges and strategies, 7EWLM, Brussels, 2018Poster
Scientists, PhD students and studentsE. Koch, A. I. Ostermann, M. Mainka, C. Dalle, C. Gladine, N. H. Schebb, Challenges and strategies for the quantification of total oxylipins in biological samples, Regional conference of food chemistry, Wuppertal, Germany, 2019Poster
Scientists, PhD students and studentsE. Koch, A. I. Ostermann, M. Mainka, C. Dalle, C. Gladine, N. H. Schebb, Challenges and strategies for the quantification of total oxylipins in biological samples, Regional conference of food chemistry, Wuppertal, Germany, 2019Poster
Scientists, PhD students and studentsE. Koch, M. Mainka, A. I. Ostermann, L.-F. Fröhlich, C. Gladine, N. H. Schebb: Influence of the transitory stage during plasma generation on the pattern of total oxylipins. 48 Deutscher Lebensmittelchemikertag, 16.-18.09.2019 Dresden, Deutschland POster
Scientists, PhD students and studentsC. Dalle, M. Mainka, J. Dalloux-Chioccioli, A.I. Ostermann, M. Rothe, J.W. Newman, J. Bertrand-Michel, C. Gladine, N.H. Schebb. Comparaison inter-laboratoires de profils d’oxylipines par lipidomique ciblée dans le cadre du projet JPI-OXYGENATE, RFMF, France, 2019Poster
Scientists, PhD students and studentsDalle C, Lahaye C, Ostermann AI, Bosviel R, Barthélémy JC, Roche F, Féasson, L, Mazur A, Béchet D, Ruivard, M, Schebb, NH and Gladine, C, MS-based oxylipin targeted metabolomics: applications in clinical research, GERLI meeting, Compiègne, France, 2019Presentation
Scientists, PhD students and studentsM. Mainka, E. Koch, C. Dalle, J. Bertrand-Michel, C. Gladine and N. H. Schebb. Stability of total oxylipins influence of plasma generation and long-term storage. RFMF Metabomeeting, 22-24.01.2020 Toulouse, FrancePoster
Scientists, PhD students and studentsC Dalle, M. Mainka, J. Dalloux-Chioccioli, A. I. Ostermann, M. Rothe, J. W. Newman, J. Bertrand-Michel, C. Gladine, N. H. Schebb: MS-based targeted metabolomics of eicosanoids and other oxylipins: analytical variability and interlaboratory comparison. RFMF Metabomeeting, 22-24.01.2020 Toulouse, FrancePOster
Scientists, PhD students and studentsK. M. Rund, M. Mainka, N. M. Hartung, N. Kampschulte, C. Dalle, M. Pétéra, J. Dalloux-Chioccioli, A. I. Ostermann, M. Rothe, J. Bertrand-Michel, J. W. Newman, C. Gladine, N. H. Schebb: Towards comparable results in oxylipin analysis. Winter Eicosanoid Conference, Virtual Meeting, 2020, October 15. 2020 Poster
Scientists, industrials, PhD students and studentsRobustness and comparability of MS-based targeted metabolomics of total oxylipins: new verdict from the JPI-Oxygenate project. EU COST EpiLipidNet working group 2 Meeting, online, 2020Presentation
Scientists, industrials, PhD students and studentsCéline Dalle, Jérémy Tournayre, Malwina Mainka, Alicja Basiak-Rasała, Mélanie Pétéra, Jessica Dalloux-Chioccioli, Mélanie Deschasaux, Lucie Lécuyer, Sophie Lefèvre-Arbogast, Cécilia Samieri, Katarzyna Zatońska, Mads Fiil Hjorth, Arne Astrup, Justine Bertrand-Michel, Nils H. Schebb, Andrzej Szuba, Mathilde Touvier, John W. Newman, Cécile Gladine. Lipidomic profiling identifies consistent and performant oxylipin signatures of cardiometabolic syndrome. 9th International Singapore Lipid Symposium (iSLS9), online, 2021Presentation

4.3 List of submitted patents and other outputs

Patent licencePartners involvedYearInternational eu or national patentCommentPdf

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