Lipidomics-Based Cartography of Membrane Phospholipids Remodeling Uncovers Enzymatic Underpinnings of Cellular Dysfunction in Metabolic Syndrome Patients

Background: Metabolic syndrome (MetS) is linked with insulin resistance and low-grade chronic inflammation. Emerging evidence indicates that these features are associated with the disturbed membrane phospholipid composition but the enzymatic drivers of membrane remodeling in real-life MetS are still too poorly mapped. Objective: The overall design is to map membrane phospholipid remodeling through lipidomics and identify the enzymatic causes of cellular dysfunction of patients who have MetS. Methods: This is a hospital-based case-control study, 100 adults were witnessed (MetS, n=50; controls, n=50). Fasting clinical and biochemical parameters were measured, which included lipid profile, hs-CRP, fasting insulin and HOMA-IR. Plasma and PBMC lipid extracts were analysed by UHPLC -MS/MS lipidomics. Remodeling indices (LPC/PC, LPE/PE, saturation index, PUFA-enrichment) derived. PBMC enzymatic activities important to Lands' cycle (PLA2, LPCAT, ACSL4 and MBOAT7) were measured. Group comparisons, correction for multiple testing (fdr) correction for lipidomics, correlation and regression analysis were performed in multivariable. Results: MetS cases had greater insulin resistance and inflammation (HOMA-IR and hs-CRP; p