Shotgun lipidomics
In lipidomics, the process of shotgun lipidomics (named by analogy with shotgun sequencing) uses analytical chemistry to investigate the biological function, significance, and sequelae of alterations in lipids and protein constituents mediating lipid metabolism, trafficking, or biological function in cells. Lipidomics has been greatly facilitated by recent advances in, and novel applications of, electrospray ionization mass spectrometry (ESI/MS).
Lipidomics is a research field that studies the pathways and networks of cellular lipids in biological systems (i.e., lipidomes) on a large scale. It involves the identification and quantification of the thousands of cellular lipid molecular species and their interactions with other lipids, proteins, and other moieties in vivo. Investigators in lipidomics examine the structures, functions, interactions, and dynamics of cellular lipids and the dynamic changes that occur during pathophysiologic perturbations.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.The two major platforms currently used for lipidomic analyses are HPLC-MS and shotgun lipidomics.
History
Shotgun lipidomics was developed by Richard W. Gross, MD, PhD, and Xianlin Han, PhD., by employing ESI intrasource separation techniques. Individual molecular species of most major and many minor lipid classes can be fingerprinted and quantitated directly from biological lipid extracts without the need for chromatographic purification.
Advantages
Shotgun lipidomics is fast, highly sensitive, and it can identify hundreds of lipids missed by other methods — all with a much smaller tissue sample so that specific cells or minute biopsy samples can be examined.
Further reading
- Han X, Gross RW (2005). "Shotgun lipidomics: electrospray ionization mass spectrometric analysis and quantitation of cellular lipidomes directly from crude extracts of biological samples". Mass Spectrom Rev 24 (3): 367–412. doi:10.1002/mas.20023. PMID 15389848.
- Han X, Gross RW (April 2005). "Shotgun lipidomics: multidimensional MS analysis of cellular lipidomes". Expert Rev Proteomics 2 (2): 253–64. doi:10.1586/14789450.2.2.253. PMID 15892569.
- Han X, Gross RW (June 2003). "Global analyses of cellular lipidomes directly from crude extracts of biological samples by ESI mass spectrometry: a bridge to lipidomics". J. Lipid Res. 44 (6): 1071–9. doi:10.1194/jlr.R300004-JLR200. PMID 12671038.
References
- Gunning for fats
- Han X, Yang K, Cheng H, Fikes KN, Gross RW (July 2005). "Shotgun lipidomics of phosphoethanolamine-containing lipids in biological samples after one-step in situ derivatization". J. Lipid Res. 46 (7): 1548–60. doi:10.1194/jlr.D500007-JLR200. PMC 2141546. PMID 15834120.
- Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometric Analysis of Cellular Glycerophospholipids Enabled by Multiplexed Solvent Dependent Analyte-Matrix Interactions
- Microfluidics-based electrospray ionization enhances the intrasource separation of lipid classes and extends identification of individual molecular species through multi-dimensional mass spectrometry: development of an automated high-throughput platform for shotgun lipidomics
- Cheng H, Mancuso DJ, Jiang X, et al. (May 2008). "Shotgun lipidomics reveals the temporally dependent, highly diversified cardiolipin profile in the mammalian brain: temporally coordinated postnatal diversification of cardiolipin molecular species with neuronal remodeling". Biochemistry 47 (21): 5869–80. doi:10.1021/bi7023282. PMC 2507872. PMID 18454555.
- Yang K, Zhao Z, Gross RW, Han X (2007). "Shotgun lipidomics identifies a paired rule for the presence of isomeric ether phospholipid molecular species". In Fox, Debbie. PLoS ONE 2 (12): e1368. doi:10.1371/journal.pone.0001368. PMC 2147047. PMID 18159251.
- Gross RW, Han X (2007). "Lipidomics in diabetes and the metabolic syndrome". Meth. Enzymol. 433: 73–90. doi:10.1016/S0076-6879(07)33004-8. PMID 17954229.
- Jiang X, Cheng H, Yang K, Gross RW, Han X (December 2007). "Alkaline methanolysis of lipid extracts extends shotgun lipidomics analyses to the low-abundance regime of cellular sphingolipids". Anal. Biochem. 371 (2): 135–45. doi:10.1016/j.ab.2007.08.019. PMC 2131739. PMID 17920553.
- Sun G, Yang K, Zhao Z, Guan S, Han X, Gross RW (September 2007). "Shotgun metabolomics approach for the analysis of negatively charged water-soluble cellular metabolites from mouse heart tissue". Anal. Chem. 79 (17): 6629–40. doi:10.1021/ac070843. PMC 2981504. PMID 17665876.
- Han X, Yang J, Yang K, Zhao Z, Abendschein DR, Gross RW (May 2007). "Alterations in myocardial cardiolipin content and composition occur at the very earliest stages of diabetes: a shotgun lipidomics study". Biochemistry 46 (21): 6417–28. doi:10.1021/bi7004015. PMC 2139909. PMID 17487985.
- Mancuso DJ, Han X, Jenkins CM, et al. (March 2007). "Dramatic accumulation of triglycerides and precipitation of cardiac hemodynamic dysfunction during brief caloric restriction in transgenic myocardium expressing human calcium-independent phospholipase A2gamma". J. Biol. Chem. 282 (12): 9216–27. doi:10.1074/jbc.M607307200. PMID 17213206.
- Han X, Yang K, Yang J, Cheng H, Gross RW (April 2006). "Shotgun lipidomics of cardiolipin molecular species in lipid extracts of biological samples". J. Lipid Res. 47 (4): 864–79. doi:10.1194/jlr.D500044-JLR200. PMC 2147724. PMID 16449763.
- Han X, Yang K, Yang J, Fikes KN, Cheng H, Gross RW (February 2006). "Factors influencing the electrospray intrasource separation and selective ionization of glycerophospholipids". J. Am. Soc. Mass Spectrom. 17 (2): 264–74. doi:10.1016/j.jasms.2005.11.003. PMID 16413201.
- Han X, Yang J, Cheng H, Yang K, Abendschein DR, Gross RW (December 2005). "Shotgun lipidomics identifies cardiolipin depletion in diabetic myocardium linking altered substrate utilization with mitochondrial dysfunction". Biochemistry 44 (50): 16684–94. doi:10.1021/bi051908a. PMID 16342958.
- Han X, Yang J, Cheng H, Ye H, Gross RW (July 2004). "Toward fingerprinting cellular lipidomes directly from biological samples by two-dimensional electrospray ionization mass spectrometry". Anal. Biochem. 330 (2): 317–31. doi:10.1016/j.ab.2004.04.004. PMID 15203339.