The Plasma Oxylipin Signature Provides a Deep Phenotyping of Metabolic Syndrome Complementary to the Clinical Criteria

Céline Dalle (1) , Jérémy Tournayre (1) , Malwina Mainka (2) , Alicja Basiak-Rasała (3) , Mélanie Pétéra (4, 1) , Sophie Lefèvre-Arbogast (5) , Jessica Dalloux-Chioccioli (6, 7) , Mélanie Deschasaux-Tanguy (8) , Lucie Lécuyer (8) , Emmanuelle Kesse-Guyot (8) , Léopold K Fezeu (8) , Serge Hercberg (8) , Pilar Galan (8) , Cécilia Samieri (5) , Katarzyna Zatońska (3) , Philip C Calder (9, 10) , Mads Fiil Hjorth (11) , Arne Astrup (11) , André Mazur (1) , Justine Bertrand-Michel (6, 7) , Nils Helge Schebb (2) , Andrzej Szuba (3) , Mathilde Touvier (8) , John W Newman (12, 13) , Cécile Gladine (1)

1 UNH - Unité de Nutrition Humaine
2 University of Wuppertal
3 Wrocław Medical University
4 PFEM - Plateforme Exploration du Métabolisme
5 BPH - Bordeaux population health
6 MetaboHUB-MetaToul
7 UPS/Inserm U1297 - I2MC - Institut des Maladies Métaboliques et Casdiovasculaires
8 EREN [CRESS - U1153 / UMR_A 1125] - Nutritional Epidemiology Research Team | Equipe de Recherche en Epidémiologie Nutritionnelle
9 University Hospital Southampton NHS Foundation Trust
10 University of Southampton
11 Novo Nordisk Inc
12 UC Davis - University of California [Davis]
13 Western Human Nutrition Research Center

Metabolic syndrome (MetS) is a complex condition encompassing a constellation of cardiometabolic abnormalities. Oxylipins are a superfamily of lipid mediators regulating many cardiometabolic functions. Plasma oxylipin signature could provide a new clinical tool to enhance the phenotyping of MetS pathophysiology. A high-throughput validated mass spectrometry method, allowing for the quantitative profiling of over 130 oxylipins, was applied to identify and validate the oxylipin signature of MetS in two independent nested case/control studies involving 476 participants. We identified an oxylipin signature of MetS (coined OxyScore), including 23 oxylipins and having high performances in classification and replicability (cross-validated AUCROC of 89%, 95% CI: 85–93% and 78%, 95% CI: 72–85% in the Discovery and Replication studies, respectively). Correlation analysis and comparison with a classification model incorporating the MetS criteria showed that the oxylipin signature brings consistent and complementary information to the clinical criteria. Being linked with the regulation of various biological processes, the candidate oxylipins provide an integrative phenotyping of MetS regarding the activation and/or negative feedback regulation of crucial molecular pathways. This may help identify patients at higher risk of cardiometabolic diseases. The oxylipin signature of patients with metabolic syndrome enhances MetS phenotyping and may ultimately help to better stratify the risk of cardiometabolic diseases.

Mots clés: oxylipins; lipid mediators; lipidomics; metabolic syndrome; metabolic phenotyping

Domaines: Alimentation et Nutrition; Biochimie, Biologie Moléculaire

Céline Dalle, Jérémy Tournayre, Malwina Mainka, Alicja Basiak-Rasała, Mélanie Pétéra, et al.. The Plasma Oxylipin Signature Provides a Deep Phenotyping of Metabolic Syndrome Complementary to the Clinical Criteria. International Journal of Molecular Sciences, 2022, 23 (19), pp.11688. ⟨10.3390/ijms231911688⟩. ⟨hal-03839966⟩