Targeted lipidomics

Tan B, Bradshaw HB, Rimmerman N et al. Targeted lipidomics Discovery of new fatty acyl amides. AAPS Journal 8, E461-E465, 2006. 

The global lipidomics analyses by MS can be further divided to untargeted, focused, and targeted lipidomics. The untargeted lipidomics method aims to detect all lipids (or a certain type of lipid) contained in an... 

TARGETED LIPIDOMICS AS A TOOL TO INVESTIGATE ENDOCANNABINOID FUNCTION... 

C. Application of Targeted Lipidomics for the Study of Endocannabinoid Metabolism... 

Fig. 1. Targeted lipidomics of anandamide metabolism. Postulated pathways of anandamide metabolism. Abbreviations PC, phosphatidylcholine PE, phosphatidylethanolamine NAT, JV-acyl transferase LPA, lysophosphatidic acid PA, phosphatidic acid NAPE, jV-acyl-phosphatidylethanolamine Lyso-NAPE, l-lyso,2-acyl-OT-glycero-3-phosphoethanolamine-JV-acyl ABHD-4, a//3 hydrolase-4 GP-anandamide, glycerophospho-anandamide PAEA, phospho-anandamide PLA, phospholipase A NAPE-PLD, NAPE phospholipase D PLC, phospholipase C FAAH, fatty acid amide hydrolase P, phosphatase COX, cyclooxygenase LOX, lipoxygenase CYP450, cytochrome P450 PDE, phosphodiesterase.

Fig. 2. Targeted lipidomics of 2-AG metabolism. Postulated pathways for 2-AG metabolism. Abbreviations PLC, phospholipase C DAG, diacylglycerol DGL, diacylglycerol lipase MGL, monoacylglycerol lipase PLA, phospholipase A AT, acyltransferase TAGL, triacylglycerol lipase PIP2, phosphatidylinositol bisphosphate ABHD-6/12 hydrolase lyso-PL, lysophospholipid lyso-PA, lysophosphatidic acid PA, phosphatidic add P, phosphatase COX, cydooxygen-ase LOX, lipoxygenase CYP450, cytochrome P450 CDP, cytidine diphosphate.

Highly sensitive targeted lipidomic approaches are rapidly leading to the identification of new analogs of anandamide (Tan et al., 2006). The two major families of lipids that share common chemical structure with anandamide are FAEs and fatty acid amides. Although many of these lipids show no activity at CB receptors, they are known to bind and activate other receptors, such as transient receptor potential vanilloid type-1 (TRPV-1) and the nuclear receptor peroxisome proliferator-activated (PPAR-a). 

DAG species are derived from three main routes (1) PLC-mediated hydrolysis of phospholipids (2) phosphatase-mediated hydrolysis of phosphatidic acid (PA) and (3) lipase-mediated hydrolysis of triacylglycerol (TAG) species (Fig. 2). Targeted lipidomic analyses show that the fatty acid compositions of the DAGs formed by these various routes reflect the composition of the parent lipid (Fig. 5). In particular, those derived from inositol phospholipids are highly enriched in... 

Using a combination of genetic and targeted lipidomic approaches we recently determined the role of DGL in metabotropic glutamate receptor-dependent 2-AG mobilization (Jung et al, 2007). However, the relative importance of other biosynthetic routes for the biosynthesis of 2-AG is still under investigation. 

Targeted lipidomics is leading to a better understanding of endocannabinoid metabolism. Recent innovations in LC/MS analyses have led to the rapid identification and quantification of numerous lipids, and these data are creating new opportunities to enhance our knowledge of endocannabinoid function in the context of lipid metabolism. 

The LC-MS analysis of these compounds is briefly reviewed in this section. Balazy [33] reviewed the analysis of eicosanoids in terms of targeted lipidomics. 

M. Balazy, Eicosanomics target lipidomics of eiconasoids in biological systems. Prostaglandins Lipid Mediators, 73 (2004) 173. 

S.H Lee, M.V. Williams, R.N. DuBois, LA. Blair, Targeted lipidomics using ECNI-MS, Rapid Commun. Mass Spectrom., 17 (2003) 2168. 

Figure 2.15 MS spectrum (532->453->) of GP-tagged 24S,25-epoxycholesterol. The spectrum was recorded on an LTQ Orbitrap XL. (Reproduced with permission from Wang, Y. et al, 2009, Targeted Lipidomic Analysis of Oxysterols in the Embryonic Central Nervous System, Mol. Biosyst. May 5 529-41.)...

Gruber, F., Bicker, W., Oskolkova, O. V., Tschachler, E., and Bochkov, V. N. 2012. A simplified procedure for semi-targeted lipidomic analysis of oxidized phosphatidylchohnes induced by UVA irradiation. 53,1232-42. 

Lee, S.H., Williams, M.V., DuBois, R.N. and Blair, LA. (2003) Targeted lipidomics using electron capture atmospheric pressure chemical ionization mass spectrometry. Rapid Com-mun. Mass Spectrom. 17, 2168-2176. 

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