Lipid mediator informatics-lipidomics: Novel pathways in mapping resolution

Abstract

A BSTRACTLipidomics, the systematic decoding of lipid-based information in biosystems, is composed of identifying and profi ling lipids and lipid-derived mediators. As currently practiced, lipidomics can be subdivided into architecture/ membrane lipidomics and mediator lipidomics. The mapping of structural components and their relation to cell activation as well as generation of potent lipid mediators and networks involves a mass spectrometry -computational approach so that interrelationships and complex mediator networks important for cell homeostasis can be appreciated. Cell membranes are composed of a bilayer that contains phospholipids, fatty acids, integral membrane proteins, membrane-associated proteins, sphingolipids, and so on. The membrane composition of many cell types has been established. The components ' organization and effect on cell function remains to be established, however, and is a quest for lipidomics. Here, we review liquid chromatography tandem mass spectrometry-based lipidomic analyses to address bioactive lipid mediators in signaling pathways and the roles of lipid-derived mediators in resolution of infl ammation.

Novel Lipid Mediators and Resolution Mechanisms in Acute Inflammation

“…They were initially identified and elucidated using LC-MS-MS-based lipidomics 8,9 and informatics 114 together with bioassay systems. The term resolvins (resolution-phase interaction products) refers to endogenous chemical mediators that are biosynthesized from the major -3 fatty acids, EPA and DHA, denoted E series (RvE) and D series (RvD) resolvins, respectively.…”

Resolvins: Natural agonists for resolution of pulmonary inflammation

“…The mouse dorsal air pouch is an experimental model of a dermal wound that provides a creative system for investigation of cellular and biochemical effectors of resolution during a self-limited acute inflammatory response. Inflammatory exudates were extracted and subjected to LC-UV-MS-MS-based lipidomic analyses by Serhan and colleagues, leading to the identification of E- and D-series resolvins (reviewed in [89]). Detailed matching studies for pro-resolving actions were performed to confirm the structure-activity relationships for each endogenous compound.…”

n-6 and n-3 Fatty Acids and Atherosclerosis

“…4 In animal models, n-3 FA-rich diets markedly decrease arterial low-density lipoprotein cholesterol deposition 5 in contrast to saturated fat-rich diets, which increase arterial wall cholesterol. 6 In addition to producing potent anti-inflammatory docosanoid catabolites, 7,8 n-3 FA may also be direct ligands for transcription factors 9 and/or may interact with specific receptors important in inflammatory cascades and insulin resistance, 10 pathways important in coronary heart disease. Of note, arachidonic acid also leads to synthesis of potent anti-inflammatory and proresolution lipoxins.…”

“…Of note, arachidonic acid also leads to synthesis of potent anti-inflammatory and proresolution lipoxins. 7 Not all intervention studies have shown the cardiovascular benefit of increased intakes of n-3 FA. This may relate, in part, to initial high baseline intakes in tissue levels of n-3 FA in certain populations (eg, Japanese individuals); short duration of interventions; small cohort sizes; a comparison of n-3 FA intervention studies using increasing intakes of ␣-linolenic acid (the essential FA precursor for EPA and DHA) with studies in which EPA and DHA are administered themselves; and studies that do not consider the baseline intakes of n-6 FA.…”