Quantitative lipidomics using metabolic deuterium oxide labeling

Abstract

Understanding changes in lipid levels between healthy and diseased states is crucial for uncovering disease mechanisms and identifying potential markers for lipid-related diseases. The quantitative analysis of these lipid changes offers insights into the underlying pathophysiology and can aid in the identification of biomarkers associated with various lipid metabolism-related conditions. Mass spectrometry, when combined with stable isotope labeling techniques, serves as a powerful tool for quantifying changes in lipid composition and dynamics. Deuterium oxide (D2O), also known as heavy water, stands out as a particularly attractive labeling agent for quantitative lipidomics. Compared to traditional methods that rely on complete replacement of light isotopes with heavier counterparts, D2O offers several advantages. First, it is significantly more cost-effective due to its readily available nature. Second, its administration is simple and non-invasive, making it amenable to various experimental designs. Finally, D2O boasts a unique advantage in its ability to uniformly label all major lipid classes, providing a comprehensive picture of the lipidome. This presentation will explain the key features and uses of D2O labeling in quantitative lipidomics, including how it allows us to measure how quickly lipids are replaced within a cell or organism and their relative abundance. Furthermore, we detail the principle of D2O labeling for global omics relative quantification (DOLGOReQ), an innovative quantitative omics strategy that utilizes partial metabolic D2O labeling. DOLGOReQ enables the relative quantification of various biomolecules beyond lipids, broadening its application in multi-omics studies.