Metabolic Deuterium Oxide Labeling for Quantitative Lipidomics

Abstract

Quantitative analysis of lipid changes between normal and disease states plays a pivotal role in unraveling the underlying pathophysiology and identifying potential biomarkers associated with lipid metabolism-related diseases. Mass spectrometry coupled with stable isotope-labeling techniques offers a powerful approach for quantitative lipidomics. Among the stable isotope-labeling options, deuterium oxide (D2O) stands out as an attractive precursor for metabolic labeling of lipids due to its cost-effectiveness, ease of administration, and ability to label all lipid classes. Unlike traditional full metabolic labeling methods, which involve complete substitution of light isotopes with heavy ones, D2O serves as a partially enriched stable isotope-labeling precursor in metabolic D2O labeling experiments. This presentation focuses on elucidating the characteristics and applications of metabolic D2O labeling in quantitative lipidomics, including measurements of turnover rates and relative quantification of lipids. Moreover, we introduce in detail the principle of D2O labeling for global omics relative quantification (DOLGOReQ), an innovative quantitative omics strategy that leverages partial metabolic D2O labeling. DOLGOReQ enables the relative quantification of various biomolecules beyond lipids, expanding its utility in multi-omics investigations.