Methodological requirements for lipidomics research

Lipidomics is a rapidly growing field that focuses on the large-scale identification and quantitation of individual lipid molecular species in biological systems. Through identification of alterations in lipid content and metabolic flux, substantial insight has been gathered regarding the chemical mechanisms that facilitate physiological adaptation during health or alternatively result in maladaptive alterations that initiate or propagate disease states. The successful performance of lipidomic studies requires the use of sample preparation methods that result in unbiased extraction of the multiplicity of lipid molecular species present within cells, the use of robust mass spectrometry (MS) methods with quantitation by ratiometric comparisons with appropriate internal standards, and the use of novel bioinformatic approaches that maximize the information content that can be mined from MS data sets (see Chapter 19 for phospholipidomics by ³¹P NMR spectroscopy). Through more recent technological advances in sample preparation, MS instrumentation, and bioinformatics, the expanding role of lipidomics in systems biology approaches to identify biomarkers of disease and the chemical mechanisms underlying disease processes has become apparent. Cellular membranes are composed of a diverse array of distinct lipid molecular species that modulate the biochemical and biophysical characteristics of cellular membrane bilayers. Through the combined use of hundreds of distinct aliphatic chains and polar head groups, which are covalently linked to glycerol or sphingosine backbones, many tens of thousands of individual lipid molecular species are present in biological tissues, cells, and fluids (Figure 2.1). Evolution has used this rich repertoire of lipids to modulate membrane function through lipids’ prominent effects on membrane structure, dynamics, and surface charge. This large diversity of lipid molecular species results in a rich panoply of membrane microenvironments that “allows” each cell the metabolic and biophysical flexibility to adapt to physiological perturbations in health or, alternatively, can precipitate pathological alterations in membrane structure and function during disease processes.