As part of the LIPID MAPS Consortium, our laboratory has developed a rigorous, comprehensive approach to the lipidomic analysis of hundreds of fatty acids, acylethanolamines and inflammatory eicosanoids, including their many metabolites resulting from the reactions of a range of cyclooxygenases, lipoxygenases, cytochrome P450s and non-enzymatic oxidation to produce both single and combined isoprostanes.
This lipidomic analysis has enabled us to characterize cellular lipid signaling byToll-like receptors (TLRs) and purine receptors, and their "synergy" in endotoxin-activated macrophages, in order to model infection and inflammation. Advances in our understanding of the mechanisms of the inflammatory response and the central role of eicosanoids have been facilitated by recent experiments comparing various primary macrophages with cell lines, as well as through the analysis of metabolite fluxes in macrophages and their proteomic analysis. Lipidomic analysis of cells supplemented with small quantities of omega-3 fatty acids - eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) - provides information on the general effects of EPA and DHA on inflammatory eicosanoids and their mechanisms of action. EPA and DHA are also essential for the synthesis of very long fatty acid chains, which play a central role in retinal function.
