Recent advances in expanding the coverage of the lipidome

Abstract

The lipidome comprises a large array of molecules with diverse physicochemical properties. Lipids are structural components of cells, act as a source of energy, and function as signaling mediators. Alterations in lipid metabolism are involved in the onset and progression of a variety of diseases, including metabolic syndrome and cancer. Because of this, interest in lipidomics, the comprehensive characterization of the lipidome by mass spectrometry, has intensified in recent years. However, obtaining a truly complete overview of all lipids in a sample has remained very challenging due to their enormous structural diversity. Here, we provide an overview of the collection of analytical approaches used to study various lipid classes, emphasizing innovations in sample preparation and liquid chromatography-mass spectrometry (LC-MS). Additionally, we provide practical suggestions for increasing the coverage of the lipidome.

Graphical abstract

Figure 1

Commonly used extraction procedures in lipidomics and the lipid classes they cover. Published methods include chloroform and methyl tert-butyl ether (MTBE) based extractions [23, 24, 28, 29, 30, 31, 32], butanol and butanol-methanol (BUME) extraction procedures [17, 25, 33, 34, 35], and an extraction procedure using acetic acid (AcOH) with isopropanol and hexane [9^••]. (L)PC, (lyso)phosphatidylcholine; (L)PE, (lyso)phosphatidylethanolamie; (L)PG, (lyso)phosphatidylglycerol; (L)PI, (lyso)phosphatidylinositol; (L)PS, (lyso)phosphatidylserine; AcCN, acyl-carnitine; FAHFA, branched fatty acid esters of hydroxy fatty acid; Cer, ceramide; So, sphingosine; (L)SM, (lyso)sphingomyelin; DG, diglyceride; TG, triglyceride; CE, cholesterol ester; (L)PA, (lyso)phosphatidic acid; cPA, cyclic phosphatidic acid; CL, cardiolipin; CerP, ceramide-phosphate; S(1)P, sphingosine-1-phosphate; BMP, bis(monoglyceride)phosphate; MG, monoglyceride; GluCer, glucosyl-ceramide; LacCer, lactosyl-ceramide; FA, fatty acid; oxPL, oxidized phospholipids; GL, glycerides; PL, phospholipids; PK, polyketides; PR, prenols; SL, sphingolipids.

Figure 2

Coverage of the (a) apolar, and (b) polar lipid classes by commonly used separation methods. RP, reversed phase; ACN, acetonitrile; IPA, isopropanol; NP, normal phase; HILIC, hydrophilic interaction liquid chromatography; CE, cholesterol ester; TG, triglyceride; (L)SM, (lyso)sphingomyelin; DG, diglyceride; (L)PC, (lyso)phosphatidylcholine; PE, phosphatidylethanolamine; (L)PS, (lyso)phosphatidylserine; (L)PG, (lyso)phosphatidylglycerol; (L)PI, (lyso)phosphatidylinositol; Cer, ceramide; MG, monoglyceride; So, sphingosine; S1P, sphingosine-1-phosphate; FA, fatty acid; AcylCN, acyl-carnitine.