Metabolic Pathway of Monounsaturated Lipids Revealed by In-depth Structural Lipidomics by Mass Spectrometry

Study of lipid metabolism relies on characterization of the lipidome, which is quite complex due to the structure variations of the lipid species. New analytical tools have been developed recently for characterizing fine structures of lipids, with C=C location identification as one of the major improvements. In this study, we studied the lipid metabolism reprograming by analyzing glycerol phospholipid (GP) compositions in breast cancer cell lines with structural specification extended to C=C location level. Inhibition of the lipid desaturase, stearoyl-CoA desaturase 1 (SCD1), increased the proportion of n-10 isomers that are produced via an alternative fatty acid desaturase 2 (FADS2) pathway. However, there were different variations of the ratio of n-9/n-7 isomers in C18:1-containing glycerol phospholipids (GPs) after SCD1 inhibition, showing increased tendency in MCF-7 cells, MDA-MB-468 cells, and BT-474 cells, but decreased tendency in MDA-MB-231 cells. No consistent change of the ratio of n -9/n- 7 isomers was observed in SK-BR-3 cells. This type of heterogeneity in reprogrammed lipid metabolism can be rationalized by considering both lipid desaturation and fatty acid oxidation (FAO), highlighting the critical roles of comprehensive lipid analysis in both fundamental and biomedical applications.