Human plasma lipids: The alpha to omega
Lipidomics Gateway (22 September 2010) [doi:10.1038/lipidmaps.2010.28]
Over 500 lipid species have been identified and quantified in human blood plasma.
Relationships between mammalian lipid categories and the 2-carbon precursor acetyl CoA. Fatty acyl-derived subsituents are colored green; isoprene-derived atoms are colored purple; glycerol and serine-derived groups are colored red and blue, respectively. Values in yellow ovals represent the number of analytes within each lipid category that were quantified by mass spectrometry in the human plasma sample. Quehenberger, O. et al. J. Lipid Res. (29 July 2010) doi:10.1194/jlr.M009449
Considerable attention has been paid to the links between diseases and the levels of blood plasma lipids, in particular between metabolic disease and cholesterol. Nevertheless, only partial knowledge of the lipids present in human blood plasma has been available, and until now no study has attempted to systematically analyze the full range. Now, with support from the National Institutes of Health, Edward A. Dennis and colleagues from the LIPID MAPS consortium have taken a lipidomics approach to reveal the diversity of human blood plasma lipids.
The goal of metabolomic—and lipidomic—research is to understand how the levels of cellular metabolites change in response to physiological and pathological processes, but changes cannot be detected without a benchmark for comparison. The National Institute of Standards has produced a human plasma standard reference, which Dennis and colleagues analyzed as part of the ongoing LIPID MAPS effort to define the mammalian lipidome. Different separation protocols and mass spectrometry techniques were needed for each category of lipid. Several of these techniques improve upon those already developed by the consortium.
Whereas oleic, palmitic and stearic acids constituted nearly 80% of free fatty acids, much rarer fatty acids were also precisely measured, including the nutritionally essential α-linolenic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). At much lower concentrations than free fatty acids, eicosanoids—which derive from arachidonic acid and related PUFAs by one of three synthetic pathways or by autoxidation—showed even greater diversity. The researchers also quantified a metabolite of one of these pathways that might play a role in inflammation—15deoxy Δ12,14 PGD2. Unexpectedly, most PUFA autoxidation products were derivatives of the relatively low-abundant DHA.
Constituting a high proportion of total lipids, the glycerolipid profile was dominated by triacylglycerols (TAGs). Although not every molecular species could be identified, by combining information about both chromatographic retention times and different possible isobaric species, the authors were able to detect over 200 TAG species. Ether-linked glycerolipids and diacylglycerols were also quantified.
Although these were the most abundant lipid category by weight, isobaric complications limited the accurate quantification to 160 of over 200 glycerophospholipids detected. Phosphatidylcholines and phosphatidylethanolamines—the most abundant classes by weight—contained substantial amounts of ether-linked lipids.
This diverse category was dominated by sphingomyelins (SM), which comprised around 100 subspecies, double previous estimates. Constituting just 1% of sphingolipids, ceramide monohexoses (CMH) could not be quantified to the same extent. Compared with SM and CMH, free ceramides had more very-long-chain fatty acids and less palmitic acid in their structures. Sphingosine-1-phosphate was the predominant free sphingoid base.
In this, the most abundant category by molar concentration, cholesterol and 13 less-abundant sterols were detected. With the exception of 7-dehydrocholesterol, most sterols existed in free and esterified form. Neutral cholesteryl esters were notable for their abundance.
Of the dolichol lipids, dolichol-19 was the most abundant, consistent with other studies. Of the ubiquinone class, the authors focused on CoQ9 and CoQ10, which play a role in ATP synthesis and might protect against heart disease. The reported levels were higher than in previous studies and 94% of CoQ was CoQ10.
Although much remains unknown about what specific lipid species do, or how their levels are affected by drugs, studies are continually uncovering new biological roles for unexpected lipids. Datasets such as this will be invaluable for helping to fill the gaps in knowledge. In the future, it is possible that a patient's entire blood lipid composition could be rapidly analyzed and imbalances—or their associated diseases—efficiently treated.
Samia Burridge- Copyright © 2010 Nature Publishing Group, a division of Macmillan Publishers Limited; used with permission
Original research paper
Quehenberger, O. et al. Lipidomics reveals a remarkable diversity of lipids in human plasma.
J. Lipid Res. (29 July 2010). doi:10.1194/jlr.M009449