Lipidomic analysis of human plasma reveals ether-linked lipids that are elevated in morbidly obese humans compared to lean

BACKGROUND Lipidomic analysis was performed to explore differences in lipid profiles between plasma from lean and obese subjects, followed by in vitro methods to examine a role for the identified lipids in endothelial cell pathophysiology. METHODS Plasma was collected from 15 morbidly obese and 13 control subjects. Lipids were extracted from plasma and analyzed using LC/MS, and MS/MS to characterize lipid profiles and identify lipids that are elevated in obese subjects compared to lean. RESULTS Orthogonal partial least squares-discriminant analysis (OPLS-DA) modelling showed that lipid profiles were significantly different in obese subjects compared to lean. Analysis of lipids that were driving group separation in the OPLS-DA model and that were significantly elevated in the obese group led to identification of a group of ether-linked phosphatidylcholine (PC) and phosphatidylethanolamine (PE) lipids of interest. Treatment of human coronary artery endothelial cells with the ether-linked phosphatidylethanolamine induced expression of cell adhesion molecules, a hallmark of endothelial cell activation. However, oxidized phosphatidylcholine products that can induce endothelial cell activation in vitro, were not significantly different between groups in vivo. CONCLUSION These data suggest a role for ether-linked lipids in obesity associated dyslipidemia and vascular disease.