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R E V I E W S
Lipids are essential metabolites that have many crucial cellular functions (BOX1) and can provide a direct readout of cellular metabolic status. The total lipid content in a cell is called a lipidome1, and is predicted to be in the range of tens of thousands to hundreds of thousands at concentrations of between amol/mg and nmol/mg of protein24. Lipids are divided into classes and subclasses depending on the head group and the type of linkage between the head group and aliphatic chains (FIG.1). A comprehensive list of lipid classes and subclasses, as well as the common abbreviations, can be found in the classification system provided by http://www.lipidmaps.org
Web End =Lipid http://www.lipidmaps.org
Web End =MAPS consortium 5.
Lipidomics is the study of lipidomes using the principles and techniques of analytical chemistry610, and
emerged in 2003 as an approach to study the metabolism of the cellular lipidome. The analytical power of, and new developments in, mass spectrometry (MS) have accelerated this emerging discipline11,12. Lipidomics provides a powerful tool for the development of lipid biomarkers to study disease states. Importantly, this approach enables us to study cellular metabolism by quantifying the changes of individual lipid classes, subclasses and molecular species that reflect metabolic differences. As the pathways and networks of lipid metabolism have been extensively studied13, any changes in lipid amounts can simultaneously reveal variations in several enzymatic levels, activities and/or gene expression patterns
(FIG.2). This high-throughput process is equivalent to enzymatic assays that were performed individually for each enzyme, and can ultimately identify the molecular mechanisms responsible for disease pathogenesis.
Multi-dimensional MS-based shotgun lipi domics4,11,14
is a comprehensive and accurate lipidomics approach (with ~90% accuracy15), which has enabled the identification of fatty acyl positional isomers16,17 and fatty acid isomers18, as well as the analysis of >40 lipid classes and thousands of individual lipid species19. Comprehensive analysis of lipid classes and molecular species using the separation power of liquid chromatography (LC) in LC-MS has also been performed2022. The main MS-based techniques currently used in lipidomics, which all have distinct advantages and disadvantages, are outlined in BOX2 (REFS18,2329).
This Review provides an overview of how lipidomics enables the study of lipid metabolism. Unfortunately, although the strategies to analyse the isolated pathways are...