Untargeted Lipidomics after D2O Administration Reveals the Turnover Rate of Individual Lipids in Various Organs of Living Organisms

The administration of low doses of D2O to living organisms was used for decades for the investigation of metabolic pathways and for the measurement of the turnover rate for specific compounds. Usually, the investigation of the deuterium uptake in lipids is performed by measuring the deuteration level of the palmitic acid residue using GC-MS instruments, and to our knowledge, the application of the modern untargeted LC-MS/MS lipidomics approaches was only reported a few times. Here, we investigated the deuterium uptake for >500 lipids for 13 organs and body liquids of mice (brain, lung, heart, liver, kidney, spleen, plasma, urine, etc.) after 4 days of 100% D2O administration. The maximum deuteration level was observed in the liver, plasma, and lung, while in the brain and heart, the deuteration level was lower. Using MS/MS, we demonstrated the incorporation of deuterium in palmitic and stearic fragments in lipids (PC, PE, TAG, PG, etc.) but not in the corresponding free forms. Our results were analyzed based on the metabolic pathways of lipids.

Automated summary

The administration of low doses of D2O has been used for decades to investigate metabolic pathways and measure compound turnover rate. Previously, the uptake of deuterium in lipids was mainly studied using GC-MS instruments, but recent untargeted LC-MS/MS lipidomics approaches have been employed. In this study, the deuterium uptake in over 500 lipids was investigated in 13 organs and body fluids of mice after 4 days of 100% D2O administration. The highest deuteration was observed in the liver, plasma, and lung, while lower levels were found in the brain and heart. The incorporation of deuterium in palmitic and stearic fragments in lipids was demonstrated using MS/MS, but not in the corresponding free forms. The results were analyzed based on lipid metabolic pathways.