Characterization of bulk phosphatidylcholine compositions in human plasma using side-chain resolving lipidomics

Abstract

Running title: Composition of phosphatidylcholine sums in human plasmaAbbreviations: CV, coefficient of variation; conc., concentration; mGWAS, genome-wide association study with metabolic traits, MWAS, metabolome-wide association study, OGTT, oral glucose tolerance test; OLTT, oral lipid tolerance test; PC, phosphatidylcholine; pv, p-value; R, rest that consists of the totality of nonmeasured single PCs, SD, standard deviation 3 Abstract Kit-based assays, such as AbsoluteIDQ TM p150, are widely used in large cohort studies and provide a standardized method to quantify blood concentrations of phosphatidylcholines (PCs). Many disease-relevant associations of PCs were reported using this method. However, their interpretation is hampered by lack of functionally relevant information on the detailed fatty acid side chain compositions as only the total number of carbon atoms and double bonds is identified by the kit. To enable more substantiated interpretations, we characterized these PC sums using the side chain resolving Lipidyzer TM platform, analyzing 223 samples in parallel to the AbsoluteIDQ TM . Combining these datasets, we estimated the quantitative composition of PC sums and subsequently tested their replication in an independent cohort. We identified major constituents of 28 PC sums, revealing also various unexpected compositions. As an example, PC 16:0_22:5 accounted for more than 50% of the PC sum with in total 38 carbon atoms and 5 double bonds (PC aa 38:5). For 13 PC sums, we found relatively high abundances of odd-chain fatty acids. In conclusion, our study provides insights in PC compositions in human plasma, facilitating interpretation of existing epidemiological datasets and potentially enabling imputation of PC compositions for future meta-analyses of lipidomics data.

Physiological extremes of the human blood metabolome: A metabolomics analysis of highly glycolytic, oxidative, and anabolic athletes

“…This labeling bases on the assumption that evennumbered fatty acids and lower degrees of desaturation are more common than odd-numbered fatty acids or very high degrees of desaturation. Common violations of these assumptions and observable mixed molecular compositions of measured PCs in human blood have been discussed recently in more detail (Quell et al, 2019). The assessed biologically relevant ratios include e.g.…”

“…Quell et al recently showed that blood PC aa C36:6 measured in healthy young men mainly comprises a derivative of DHA, a fatty acid with 22 carbons and 6 double bonds (C22:6). Quell et al found PCaas that contain DHA as one, and tetradecanoic acid as the second fatty acid chain (PC 14:0_22:6) account for the major part (~88%) of measured PC aa C36:6 concentrations (Quell et al, 2019). They also suggested the second PCae that was higher in natural bodybuilders (PC ae C38:0) to be a DHA derivative.…”

“…This labeling is based on the assumption that even-numbered fatty acids and lower degrees of desaturation are more common than odd-numbered fatty acids or very high degrees of desaturation. For example, the labels PC ae C38:0, PC aa C37:0, and PC aa C38:7, all have the same mass and, thus, all would describe the same PC kit measure representing a mixture of these structurally different PCs; according to the assumptions above, the respective kit measure is labeled as PC ae C38:0 (for more details see (Quell et al, 2019)).…”

“…b PC ae C38:0 is isobar (same nominal mass) with PC aa C38:7. In human plasma of young healthy men, PC ae C38:0 is considered to contain considerable amounts of PC molecules that carry a fatty acid chain with 22 carbon atoms and 6 double bonds (C22:6), same as for the related measure PC aa C36:6(Quell et al, 2019). SM (OH) C22:1 and SM (OH) C22:2 labeled as hydroxy-sphingolipids are isobar with odd-chain non-hydroxy sphingolipids (e.g.…”