Mapping the distribution of double bond location isomers in lipids across mouse tissues

Lipids are highly diverse and essential biomolecules in all living systems. As lipid homeostasis is often perturbed in metabolic diseases, these molecules can serve as both biomarkers and drug targets. The development of modern mass spectrometry (MS) provided the platform for large-scale lipidomic studies at the level of molecular species. Traditionally, more detailed structural information, such as the C=C location, was mostly assumed instead of properly measured, though the specific isomers were indicated as potential biomarkers of cancers or cardiovascular diseases. Recent C=C localization methods, including the Paternò–Büchi (PB) reaction, have shown the prevalent and heterogeneous distribution of C=C location in lipids across tissues. Mapping the lipidome of model animals at the level of C=C position would increase the understanding of the metabolism and function of lipid isomers, facilitating clinical research. In this study, we employed an online PB reaction on a liquid chromatography-high resolution MS platform to map C=C location isomers in five different murine tissues. We analyzed phosphatidylcholines, phosphatidylethanolamines, and sphingomyelins; we relatively quantified and mapped the distribution of ∼30 groups of co-existing isomers, characterized by different chain lengths and degrees of unsaturation. More specifically, we performed relative quantitation of four isomers of the C16:1 fatty acyl, which included rarely reported n-10 and n-5 species besides n-9 and n-7 isomers. We showed a small variation of the isomers’ relative composition among individual animals (<20%) but significant differences across different lipid species and mouse tissues. Our results provided an initial database to map alternative lipid metabolic pathways at the tissue level.

• The study applies the online Paternò-Büchi reaction with liquid chromatography-high resolution mass spectrometry to map C=C location isomers of phospholipids and sphingolipids in five different murine tissues.
• The study relatively quantifies and maps the distribution of ~30 lipid isomer groups, including rarely reported n-10 and n-5 isomers of C16:1 fatty acyl, providing an initial database for lipid metabolic pathways in tissues.