The plasma oxylipin signature provides a deep phenotyping of metabolic syndrome complementary to the clinical criteria

Authors: DALLE, CELINE - French National Institute For Agricultural Research; TOURNAYRE, JEREMY - Inrae; MAINKA, MALWINA - University Of Wuppertal; BASIAK-RASALA, ALICJA - Inrae; PÉTÉRA, MELANIE - French National Institute For Agricultural Research; LEFÈVRE-ARBOGAST, SOPHIE - University Of Bordeaux; DALLOUX-CHIOCCIOLI, JESSICA - Institut National De La Sante Et De La Recherche Medicale (INSERM); DESCHASAUX-TANGUY, M - French National Institute For Agricultural Research; LECUYER, LUCIE - Institut National De La Sante Et De La Recherche Medicale (INSERM); KESSE-GUYOT, EMMANUELLE - Sorbonne Universities, Paris; FEZEU, LÉOPOLD - Sorbonne Universities, Paris; HERCBERG, SERGE - Sorbonne Universities, Paris; GALAN, PILAR - Sorbonne Universities, Paris; SAMIERI, CÉCILIA - Institut National De La Sante Et De La Recherche Medicale (INSERM); ZATONSKA, KATARZYNA - Wroclaw Medical University; CALDER, PHILIP - University Of Southampton; HJORTH, MADS FIIL - University Of Copenhagen; ASTRUP, ARNE - University Of Copenhagen; MAZUR, ANDRE - Inrae; BERTAND-MICHEL, JUSTINE - Institut National De La Sante Et De La Recherche Medicale (INSERM); SCHEBB, NILS - University Of Wuppertal; SZUBA, ANDZEJ - Wroclaw Medical University; TOUVIER, MATHILDE - Institut National De La Sante Et De La Recherche Medicale (INSERM); Newman, John; GLADINE, CECILE - Inrae

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/24/2022
Publication Date: 10/2/2022
Citation: Dalle, C., Tournayre, J., Mainka, M., Basiak-Rasala, A., Pétéra, M., Lefèvre-Arbogast, S., Dalloux-Chioccioli, J., Deschasaux-Tanguy, M., Lecuyer, L., Kesse-Guyot, E., Fezeu, L., Hercberg, S., Galan, P., Samieri, C., Zatonska, K., Calder, P.C., Hjorth, M., Astrup, A., Mazur, A., Bertand-Michel, J., Schebb, N.H., Szuba, A., Touvier, M., Newman, J.W., Gladine, C. 2022. The plasma oxylipin signature provides a deep phenotyping of metabolic syndrome complementary to the clinical criteria. International Journal of Molecular Sciences. 23(19). Article 11688. https://doi.org/10.3390/ijms231911688.
DOI: https://doi.org/10.3390/ijms231911688

Interpretive Summary: Metabolic syndrome (MetS) is a complex condition encompassing a constellation of physiological dysfunctions associated with obesity, glucose regulation, and alterations in how the body generates and uses lipids. Together these metabolic complications increase an individuals risk of developing cardiovascular diseases. A link between these related but unique conditions are changes in the production and balance of small molecules the body uses to regulate inflammation, energy metabolism vascular function and cell growth. To gain a higher resolution picture of these metabolic changes, we profiled these small molecule mediators in two independent case/control studies with 476 participants. This effort uncovered and validated a signature of MetS strongly associated with this condition. Our metabolite signature provides a novel mechanistic phenotype of MetS regarding the activation and/or regulation of inflammation, oxidative stress, vascular reactivity, blood clotting, endothelial permeability, glucose homeostasis and adipogenesis that may help identifying patients at higher risk of developing MetS and cardiometabolic diseases.

Technical Abstract: Metabolic syndrome (MetS) is a complex condition encompassing a constellation of cardiometabolic abnormalities. Providing a more complete view of the molecular pathways involved in MetS would help to decipher its complexity, to deeply characterize its pathophysiology and to better stratify the risk of cardiometabolic diseases. Eicosanoids and other oxylipins are a superfamilly of lipid mediators regulating most biological processes involved in cardiometabolic health. Performing a comprehensive profiling of total circulating oxylipins in two independent case/control studies (n=476 participants), we have uncovered and validated an oxylipin signature of MetS having high performances of classification and replicability (cross-validated AUCROC of 89% and 78% in the Discovery and Replication studies respectively). Our oxylipin signature provides a unique mechanistic phenotype of MetS regarding the activation and/or feedback negative regulation of inflammation, oxidative stress, vascular reactivity, blood clotting, endothelial permeability, glucose homeostasis and adipogenesis that may help identifying patients at higher risk of cardiometabolic diseases.