Oxylipin profiling identifies a mechanistic signature of metabolic syndrome: results from two independent cohorts

Background. Metabolic syndrome (MetS) is a complex condition encompassing a constellation of cardiometabolic abnormalities. Integratively phenotyping the molecular pathways involved in MetS would help to deeply characterize its pathophysiology and to better stratify the risk of cardiometabolic diseases. Oxylipins are a superfamilly of lipid mediators regulating most biological processes involved in cardiometabolic health. Methods. A high-throughput validated mass spectrometry method allowing the quantitative profiling of over 130 oxylipins was applied to identify and validate the oxylipin signature of MetS in two independent case/control studies involving 476 participants. Results. We have uncovered and validated an oxylipin signature of MetS (coined OxyScore) including 23 oxylipins and having high performances of 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 both the oxylipins and the MetS criteria showed that the oxylipin signature brings consistent and complementary information supporting its clinical utility. Moreover, the OxyScore provides a unique mechanistic signature of MetS regarding the activation and/or negative feedback regulation of crucial molecular pathways that may help identify patients at higher risk of cardiometabolic diseases. Conclusion. Oxylipin profiling identifies a mechanistic signature of metabolic syndrome that may help to enhance MetS phenotyping and ultimately to better predict the risk of cardiometabolic diseases via a better patient stratification.