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Review
. 2011 Nov 10;365(19):1812-23.
doi: 10.1056/NEJMra1104901.

The human plasma lipidome

Oswald Quehenberger  1 , Edward A Dennis
Affiliations
Review

The human plasma lipidome

Oswald Quehenberger et al. N Engl J Med. .
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1. Relative Distribution of Biologic Molecules in Human Plasma
Amino acids and nucleic acids are shown without consideration of the contribution of proteins and DNA or RNA. The relative distribution is based on weight (grams per deciliter). Data were compiled from Lentner, Wishart et al., and Quehenberger et al.
Figure 2
Figure 2. Relative Distribution of Lipids in Human Plasma
Lipidomic analysis has identified, characterized, and quantified almost 600 lipid molecular species in human plasma. The relative distribution in each category is given on a molar basis. The nomenclature of the lipid categories conforms to the recently developed LIPID MAPS classification system.
Figure 3
Figure 3. Diversity of Human Plasma Lipids
Relationships among the major mammalian lipid categories are shown by means of representative molecules from each class as examples. The diagram starts with the 2-carbon precursor acetyl coenzyme A (CoA), which is the building block for the biosynthesis of fatty acids. (SCoA indicates the thioester bond between CoA and acetic acid.) Fatty acids, in turn, become part of complex lipids — namely, glycerolipids, glycerophospholipids, sphingolipids, and sterol lipids (as steryl esters). Some fatty acids are converted to eicosanoids. A second major biosynthetic route from acetyl CoA generates the 5-carbon isoprene precursor isopentenyl pyrophosphate, which provides the building block for the prenol and sterol lipids. (The n indicates the variable number of isoprene units.) Fatty acyl–derived substituents are shown in green, isoprene-derived atoms are shown in purple, the glycerol backbone is shown in red, and the serinederived backbone is shown in blue. Arrows indicate multistep transformations among the major lipid categories, starting with acetyl CoA. Values in parentheses indicate the number of distinct analytes within each lipid category that were quantified by means of mass spectrometry in the human plasma lipidome.
Figure 4
Figure 4. Plasma Lipids in the Metabolic Syndrome
Abnormal levels of plasma lipids and lipoproteins are important risk factors for metabolic and cardiovascular diseases and are targets for therapeutic intervention. Cells need cholesterol and triacylglycerol (TAG) derived from dietary sources and the liver for membrane synthesis and energy. These lipids circulate in the blood as lipoprotein particles, including chylomicrons, very-low-density lipoprotein (VLDL), lowdensity lipoprotein (LDL), and high-density lipoprotein (HDL). In circulating chylomicrons and VLDL, TAG undergoes hydrolysis, catalyzed by lipoprotein lipase (LPL), to generate a pool of free fatty acids (FFAs) that is used as an energy source in tissues, including muscle. Excess FFAs are stored in adipocytes in the form of TAGs. Such caloric abundance leads to an unopposed expansion of adipose tissue and, ultimately, to obesity and associated metabolic complications characterized by insulin resistance and diabetes. Stored TAG in adipocytes undergoes lipolysis on demand as a result of hormone-sensitive lipase (HSL), leading to an energy-balanced level of FFAs in plasma. In insulin resistance, adipocytes exhibit a high rate of lipolysis and are highly responsive to fat-mobilizing enzymes but respond poorly to lipolysisrestraining insulin. Furthermore, insulin resistance depresses adipocyte LPL activity; however, adipocytes from obese humans use compensatory mechanisms that increase the capacity for FFA transport and uptake. In combination with increased lipolysis, this process generates abnormally high plasma levels of FFAs, allowing their increased uptake into hepatocytes in excess of metabolic requirements, which leads to storage as TAG and results in hepatic steatosis and inflammation. Some TAGs are exported as VLDL, contributing to hypertriglyceridemia. Trans-palmitoleic acid may oppose some of these effects and may stimulate insulin sensitivity in muscle and liver. In general, saturated FFAs promote cardiac disorders and systemic inflammation, whereas n–3 FFAs prevent these effects. The contribution of LDL-derived cholesterol, in both its free form (FC) and its esterified form (CE), to the development of cardiovascular disease has been well described. HDL helps remove excess FC by reverse cholesterol transport (RCT), with the formation of CE by lecithin cholesterol acyltransferase (LCAT), and subsequent uptake of the CE by the liver. High levels of HDL are correlated with low cardiovascular risk.
Figure 5
Figure 5. Eicosanoid Metabolic Network
The number of genes and proteins in a biosynthetic pathway does not accurately reflect the enormous diversity of the lipidome. For example, in the eicosanoid biosynthetic pathways, 28 known genes and their corresponding enzymatic gene products (green dots) are responsible for the production of more than 150 bioactive lipids (yellow dots) derived from dihomo-gamma-linolenic acid (20:3), arachidonic acid (20:4), eicosapentaenoic acid (20:5), and docosahexaenoic acid (22:6), of which 76 have been detected in normal human plasma. (Fatty acids are defined by the ratio of the number of carbon atoms to the number of double bonds.) A similar discrepancy between the small numbers of genes and the correspondingly larger number of individual lipid species is observed with all other lipid categories, and overlapping enzymatic activities explain the fact that a relatively small set of enzymes generates a vast number of distinct lipid species with defined molecular structures and unique biologic functions.
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Comment in

  • The human plasma lipidome.
    Ortiz A, Sanchez-Niño MD. Ortiz A, et al. N Engl J Med. 2012 Feb 16;366(7):668; author reply 668-9. doi: 10.1056/NEJMc1114201. N Engl J Med. 2012. PMID: 22335757 No abstract available.

References

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    1. Quehenberger O, Armando AM, Brown AH, et al. Lipidomics reveals a remarkable diversity of lipids in human plasma. J Lipid Res. 2010;51:3299–305. - PMC - PubMed
    1. Dennis EA. Lipidomics joins the omics evolution. Proc Natl Acad Sci U S A. 2009;106:2089–90. - PMC - PubMed
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