Lipidomics

Han and Gross[5] first defined the field of lipidomics through integrating the specific chemical properties inherent in lipid molecular species with a comprehensive mass spectrometric approach.

In lipidomic research, a vast amount of information quantitatively describing the spatial and temporal alterations in the content and composition of different lipid molecular species is accrued after perturbation of a cell through changes in its physiological or pathological state.

Therefore, lipidomic studies play an essential role in defining the biochemical mechanisms of lipid-related disease processes through identifying alterations in cellular lipid metabolism, trafficking and homeostasis.

[7] Lipids are a diverse and ubiquitous group of compounds which have many key biological functions, such as acting as structural components of cell membranes, serving as energy storage sources and participating in signaling pathways.

Lipids may be broadly defined as hydrophobic or amphipathic small molecules that originate entirely or in part from two distinct types of biochemical subunits or "building blocks": ketoacyl and isoprene groups.

However, several protocols now exist, with newer methods overcoming the shortcomings of older ones and solving problems associated with, for example, targeted lipid isolation or high throughput data collection [11] .

This involves the use of prepacked columns containing silica or other stationary phases to separate glycerophospholipids, fatty acids, cholesteryl esters, glycerolipids, and sterols from crude lipid mixtures.

"Soft" ionization does not cause extensive fragmentation, so that comprehensive detection of an entire range of lipids within a complex mixture can be correlated to experimental conditions or disease state.

[31] The source for APCI is similar to ESI except that ions are formed by the interaction of the heated analyte solvent with a corona discharge needle set at a high electrical potential.

Profiling based on electrospray ionization tandem mass spectrometry (ESI-MS/MS) is capable of providing quantitative data and is adaptable to high throughput analyses.

[37] The powerful approach of transgenics, namely deletion and/or overexpression of a gene product coupled with lipidomics, can give valuable insights into the role of biochemical pathways.

A major challenge for lipidomics, in particular for MS-based approaches, lies in the computational and bioinformatic demands of handling the large amount of data that arise at various stages along the chain of information acquisition and processing.

[41] [42] Chromatographic and MS data collection requires substantial efforts in spectral alignment and statistical evaluation of fluctuations in signal intensities.

Within the last few years, a number of software packages have been developed by various companies and research groups to analyze data generated by MS profiling of metabolites, including lipids.

Another objective of the information technology side of lipidomics involves the construction of metabolic maps from data on lipid structures and lipid-related protein and genes.

Integration of these databases with MS and other experimental data, as well as with metabolic networks[51] offers an opportunity to devise therapeutic strategies to prevent or reverse these pathological states involving dysfunction of lipid-related processes.

Examples of various lipid species.
Schema showing detection of a fatty acid by LC-MS/MS using a linear ion-trap instrument and an electrospray (ESI) ion source.
Quantitative lipid profiles (lipidomes) of yeast Saccharomyces cerevisiae grown in different temperatures [ 36 ]