Multidimensional Mass Spectrometry Using Shotgun Lipidomics to Identify Alterations in Lipid Signaling and Metabolism in Disease States

Abstract

Lipids fulfill multiple pleiotropic roles in cellular function. Alterations in cellular lipid metabolism, trafficking and/or compartmentation contribute to the majority of mortality and morbidity in industrialized nations. Historically, lipid analysis was a time‐consuming process that required multiple sequential steps to identify and quantify a limited number of high abundance lipid molecular species. During the last 25 years, the use of mass spectrometry for global lipid analysis has revolutionized our ability to understand the role of lipids in multiple disease processes. Our laboratory has developed shotgun lipidomics procedures that can directly examine with high sensitivity the lipid composition of biologic tissues or fluids directly from their organic extracts. Through exploiting the intrinsic chemical properties of lipid classes in conjunction with intrasource separation, multidimensional mass spectrometry and array analysis, it is now possible to accurately identify and quantitate hundreds to thousands of both high and low abundance lipid molecular species directly from their biologic extracts. Through the development of multidimensional mass spectrometry, much progress has already been made in understanding the roles of alterations in lipid metabolism in many disease states including diabetic cardiomyopathy, obesity and neurodegenerative disorders. This talk will summarize progress in the lipidomics field with emphasis on the advantages and difficulties of the current approaches being employed. This research was funded by NIH Grant PO1HL57278.