Electrospray/tandem mass spectrometry for quantitative analysis of lipid remodeling in essential fatty acid deficient mice

A method utilizing electrospray ionization coupled with tandem mass spectro metry was developed as a facile and rapid method to identify and quantify l ipid remodeling in vivo. Electrospray/tandem mass spectrometric analyses we re performed on lipids isolated from liver tissue and resident peritoneal c ells from essential fatty acid sufficient and deficient mice. Essential fat ty acid deficiency was chosen as the paradigm to evaluate the methodology b ecause it epitomizes the most extreme dietary means of altering fatty acid composition of virtually all cellular lipid species. Qualitative and quanti tative changes were measured in the phospholipid and cholesterol ester spec ies directly in the chloroform/methanol lipid extract without any prior chr omatographic separation. Lipid remodeling in liver and peritoneal cells fro m essential fatty acid deficient mice was qualitatively similar in choleste rol ester, phosphatidylcholine, and phosphatidylethanolamine. The monoenoic fatty acids palmitoleic acid (16:1 n-7) and oleic acid (18:1 n-9) were inc reased markedly, whereas all n-6 and n-3 polyunsaturated fatty acids were n early depleted in phospholipid and cholesterol ester species. The n-9 polyu nsaturated fatty acid surrogate, Mead acid (20:3 n-9), substituted for arac hidonic acid (20:4 n-6) and docosahexaenoic acid (22:6 n-3) in phospholipid , but not in cholesterol ester, species. Another notable difference was tha t adrenic acid (22:4 n-6) and docosapentaenoic acid (22:5 n-6), both metabo lites of arachidonic acid, accumulated in phospholipid and cholesterol este r species of peritoneal cells, but not in liver cells, of essential fatty a cid sufficient mice. The overall body of data presented illustrates the imp lementation of electrospray/tandem mass spectrometry as a method for facile and direct quantification of changes in lipid species during lipid metabol ic studies. (C) 2000 Academic Press.