Lipidomics reveals a remarkable diversity of lipids in human plasma

Abstract

The focus of the present study was to define the human plasma lipidome and to establish novel analytical methodologies to quantify the large spectrum of plasma lipids. Partial lipid analysis is now a regular part of every patient's blood test and physicians readily and regularly prescribe drugs that alter the levels of major plasma lipids such as cholesterol and triglycerides. Plasma contains many thousands of distinct lipid molecular species that fall into six main categories including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenols. The physiological contributions of these diverse lipids and how their levels change in response to therapy remain largely unknown. As a first step toward answering these questions, we provide herein an in-depth lipidomics analysis of a pooled human plasma obtained from healthy individuals after overnight fasting and with a gender balance and an ethnic distribution that is representative of the US population. In total, we quantitatively assessed the levels of over 500 distinct molecular species distributed among the main lipid categories. As more information is obtained regarding the roles of individual lipids in health and disease, it seems likely that future blood tests will include an ever increasing number of these lipid molecules.

Fig. 1.

Human plasma lipid diversity. Relationships among the major mammalian lipid categories are shown starting with the 2-carbon precursor acetyl CoA, which is the building block in the biosynthesis of fatty acids. Fatty acyl subsituents in turn may be transferred to be part of the complex lipids, namely sphingolipids, glycerolipids, glycerophospholipids, and sterols (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 blocks for the prenol and sterol lipids. Fatty acyl-derived subsituents are colored green; isoprene-derived atoms are colored purple; glycerol and serine-derived groups are colored red and blue, respectively. Arrows denote multistep transformations among the major lipid categories starting with acetyl CoA. Values in yellow ovals represent the number of analytes within each lipid category that were quantified by mass spectrometry in the human plasma sample (see text).