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

Abstract

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.

Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022

“…Due to the elevated risk of mortality with these diseases, there is a need for strategies in its identification, prevention, and treatment within healthcare. In 2022, as evidenced in Figure 5, the bulk of research articles focussed on related diseases: CVD, 232–255 diabetes, 166,233,249,250,256–278 liver disease, 51,279–293 MetS 277,294,295 and obesity 277,295–305 …”

“…Some of these oxylipins are directly linked to key molecular pathways, including oxidative stress, inflammation, blood clotting, glucose homeostasis, and adipogenesis, providing additional information that is not provided by the current clinical diagnostic tests. A classification model of 23 oxylipins was developed to stratify patients with MetS at risk of cardiometabolic diseases 294 …”

“…Bibliometric analyses of clinical lipidomics publications in 2022 using Scopus search terms “lipidomics” AND “clinic*” on 15 th December 2022 …”

“…Bibliometric analyses of clinical lipidomics publications in 2022 according to separation techniques, detectors, and RPLC columns used …”

“…,51,[279][280][281][282][283][284][285][286][287][288][289][290][291][292][293] MetS277,294,295 and obesity 277,[295][296][297][298][299][300][301][302][303][304][305]. Coleman et al investigated the pathogenesis and involvement of the gastrointestinal tract with the syndrome through multiple experiments including an untargeted RPLC-MS/MS analysis of faecal samples of people with MetS and healthy controls.…”