Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The emerging field of lipidomics

An Erratum to this article was published on 01 September 2005

Key Points

  • Lipids are important small-molecule metabolites that have roles in a wide variety of physiological processes.

  • Deregulation of lipid metabolism leads to onset of pathology, including many forms of cancer, diabetes and neurodegenerative diseases.

  • Genetics, cell biology and biochemistry have fundamentally advanced our understanding of the biology of lipids in recent years.

  • Novel methodologies for the biochemical analysis of lipids and their effectors will substantially further the field of lipid research, in particular at systems-level scale (lipidomics) approaches.

  • These technologies are valuable tools at various stages of the drug development process, most importantly in target discovery and biomarker development.

  • One of the major advantages of biochemical lipidomics, which aims at measuring lipid metabolites and their effectors, is that it might directly lead to the identification pathways of lipid action or lipid metabolism.


The crucial role of lipids in cell, tissue and organ physiology is demonstrated by a large number of genetic studies and by many human diseases that involve the disruption of lipid metabolic enzymes and pathways. Examples of such diseases include cancer, diabetes, as well as neurodegenerative and infectious diseases. So far, the explosion of information in the fields of genomics and proteomics has not been matched by a corresponding advancement of knowledge in the field of lipids, which is largely due to the complexity of lipids and the lack of powerful tools for their analysis. Novel analytical approaches — in particular, liquid chromatography and mass spectrometry — for systems-level analysis of lipids and their interacting partners (lipidomics) now make this field a promising area of biomedical research, with a variety of applications in drug and biomarker development.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1
Figure 2: Lipidomics — systems-level scale analysis of lipids and their interactors.
Figure 3: The molecular biology of lipids.
Figure 4: Mass spectrometric profiling of lipids in complex mixtures derived from tissue and cell extracts.
Figure 5: Lipidomics in drug development.


  1. 1

    Wilson, J. F. Long-suffering lipids gain respect. The Scientist 17, 34–46 (2003).

    Google Scholar 

  2. 2

    Lagarde, M., Geloen, A., Record, M., Vance, D. & Spener, F. Lipidomics is emerging. Biochim. Biophys. Acta 1634, 61 (2003).

    CAS  PubMed  Google Scholar 

  3. 3

    Feng, L. & Prestwich, G. D. (eds) Functional Lipidomics (Dekker-CRC, New York, 2005). First comprehensive reference text on various aspects of functional lipidomics with contributions from leading researchers in the field.

    Google Scholar 

  4. 4

    Glomset, J. A. Protein–lipid interactions on the surfaces of cell membranes. Curr. Opin. Struct. Biol. 9, 425–427 (1999).

    CAS  PubMed  Google Scholar 

  5. 5

    Scott, D. L. & Sigler, P. B. Structure and catalytic mechanism of secretory phospholipases A2. Adv. Protein Chem. 45, 53–88 (1994).

    CAS  PubMed  Google Scholar 

  6. 6

    Gelb, M. H., Min, J. H. & Jain, M. K. Do membrane-bound enzymes access their substrates from the membrane or aqueous phase: interfacial versus non-interfacial enzymes. Biochim. Biophys. Acta 1488, 20–27 (2000).

    CAS  PubMed  Google Scholar 

  7. 7

    Rao, V. D., Misra, S., Boronenkov, I. V., Anderson, R. A. & Hurley, J. H. Structure of type IIbeta phosphatidylinositol phosphate kinase: a protein kinase fold flattened for interfacial phosphorylation. Cell 94, 829–839 (1998).

    CAS  Google Scholar 

  8. 8

    Tsujishita, Y., Guo, S., Stolz, L. E., York, J. D. & Hurley, J. H. Specificity determinants in phosphoinositide dephosphorylation: crystal structure of an archetypal inositol polyphosphate 5-phosphatase. Cell 105, 379–389 (2001).

    CAS  PubMed  Google Scholar 

  9. 9

    Roberts, M. F. Phospholipases: structural and functional motifs for working at an interface. FASEB J. 10, 1159–1172 (1996).

    CAS  PubMed  Google Scholar 

  10. 10

    Kunz, J. et al. The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity. Mol. Cell 5, 1–11 (2000).

    CAS  PubMed  Google Scholar 

  11. 11

    Goni, F. M. & Alonso, A. in Lipases and Phospholipases in Drug Development (eds Muller, G. & Petry, S.) 79–100 (Wiley-VCH, Weinheim, Germany, 2004).

    Google Scholar 

  12. 12

    Israelachvili, J. N. Refinement of the fluid-mosaic model of membrane structure. Biochim. Biophys. Acta 469, 221–225 (1977).

    CAS  PubMed  Google Scholar 

  13. 13

    Duzgunes, N., Straubinger, R. M., Baldwin, P. A., Friend, D. S. & Papahadjopoulos, D. Proton-induced fusion of oleic acid-phosphatidylethanolamine liposomes. Biochemistry 24, 3091–3098 (1985).

    CAS  PubMed  Google Scholar 

  14. 14

    Chernomordik, L., Kozlov, M. M. & Zimmerberg, J. Lipids in biological membrane fusion. J. Membr. Biol. 146, 1–14 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15

    Feigenson, G. W. & Buboltz, J. T. Ternary phase diagram of dipalmitoyl-PC/dilauroyl-PC/cholesterol: nanoscopic domain formation driven by cholesterol. Biophys. J. 80, 2775–2788 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16

    Berridge, M. J. Inositol trisphosphate and calcium signaling. Nature 361, 315–325 (1993).

    CAS  Google Scholar 

  17. 17

    Tanaka, C. & Nishizuka, Y. The protein kinase C family for neuronal signaling. Annu. Rev. Neurosci. 17, 551–567 (1994).

    CAS  Google Scholar 

  18. 18

    Luo, B., Regier, D. S., Prescott, S. M. & Topham, M. K. Diacylglycerol kinases. Cell Signal. 16, 983–989 (2004).

    CAS  PubMed  Google Scholar 

  19. 19

    Athenstaedt, K. & Daum, G. Phosphatidic acid, a key intermediate in lipid metabolism. Eur. J. Biochem. 266, 1–16 (1999).

    CAS  PubMed  Google Scholar 

  20. 20

    Shears, S. B. How versatile are inositol phosphate kinases? Biochem. J. 377, 265–280 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21

    Balazy, M. Eicosanomics: targeted lipidomics of eicosanoids in biological systems. Prostaglandins Other Lipid Mediat. 73, 173–180 (2004).

    CAS  PubMed  Google Scholar 

  22. 22

    Barenholz, Y. Sphingomyelin and cholesterol: from membrane biophysics and rafts to potential medical applications. Subcell. Biochem. 37, 167–215 (2004).

    CAS  PubMed  Google Scholar 

  23. 23

    Pettus, B. J., Chalfant, C. E. & Hannun, Y. A. Sphingolipids in inflammation: roles and implications. Curr. Mol. Med. 4, 405–418 (2004).

    CAS  PubMed  Google Scholar 

  24. 24

    Reynolds, C. P., Maurer, B. J. & Kolesnick, R. N. Ceramide synthesis and metabolism as a target for cancer therapy. Cancer Lett. 206, 169–180 (2004).

    CAS  PubMed  Google Scholar 

  25. 25

    Hla, T. Physiological and pathological actions of sphingosine 1-phosphate. Semin. Cell Dev. Biol. 15, 513–520 (2004).

    CAS  PubMed  Google Scholar 

  26. 26

    Kee, T. H., Vit, P. & Melendez, A. J. Sphingosine kinase signalling in immune cells. Clin. Exp. Pharmacol. Physiol. 32, 153–161 (2005).

    CAS  PubMed  Google Scholar 

  27. 27

    Takenawa, T. & Itoh, T. Phosphoinositides, key molecules for regulation of actin cytoskeletal organization and membrane traffic from the plasma membrane. Biochim. Biophys. Acta 1533, 190–206 (2001).

    CAS  PubMed  Google Scholar 

  28. 28

    Wenk, M. R. & De Camilli, P. Inaugural article: Protein–lipid interactions and phosphoinositide metabolism in membrane traffic: Insights from vesicle recycling in nerve terminals. Proc. Natl Acad. Sci. USA 101, 8262–8269 (2004).

    CAS  PubMed  Google Scholar 

  29. 29

    Hurley, J. H. & Meyer, T. Subcellular targeting by membrane lipids. Curr. Opin. Cell Biol. 13, 146–152 (2001).

    CAS  Google Scholar 

  30. 30

    Balla, T. & Varnai, P. Visualizing cellular phosphoinositide pools with GFP-fused protein- modules. Sci STKE L3 (2002).

  31. 31

    van Rossum, D. B. et al. Phospholipase Cγ1 controls surface expression of TRPC3 through an intermolecular PH domain. Nature 434, 99–104 (2005).

    CAS  Google Scholar 

  32. 32

    Godi, A. et al. FAPPs control Golgi-to-cell-surface membrane traffic by binding to ARF and PtdIns(4)P. Nature Cell Biol. 6, 393–404 (2004).

    CAS  Google Scholar 

  33. 33

    Simonsen, A., Wurmser, A. E., Emr, S. D. & Stenmark, H. The role of phosphoinositides in membrane transport. Curr. Opin. Cell Biol. 13, 485–492 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34

    Rudge, S. A., Anderson, D. M. & Emr, S. D. Vacuole size control: regulation of PtdIns(3, 5)P2 levels by the vacuole-associated Vac14-Fig4 complex, a PtdIns(3, 5)P2-specific phosphatase. Mol. Biol. Cell 15, 24–36 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35

    Stone, S. J. et al. Lipopenia and skin barrier abnormalities in DGAT2-deficient mice. J. Biol. Chem. 279, 11767–11776 (2004).

    CAS  PubMed  Google Scholar 

  36. 36

    Shi, Y. & Burn, P. Lipid metabolic enzymes: emerging drug targets for the treatment of obesity. Nature Rev. Drug Discov. 3, 695–710 (2004).

    CAS  Google Scholar 

  37. 37

    Muller, G. in Lipases and Phospholipases in Drug Development 231–331 (Wiley-VCH, Weinheim, Germany, 2004).

    Google Scholar 

  38. 38

    Hollander, P. Orlistat in the treatment of obesity. Prim. Care 30, 427–440 (2003).

    PubMed  Google Scholar 

  39. 39

    Clement, S. et al. The lipid phosphatase SHIP2 controls insulin sensitivity. Nature 409, 92–97 (2001).

    CAS  Google Scholar 

  40. 40

    Sleeman, M. W. et al. Absence of the lipid phosphatase SHIP2 confers resistance to dietary obesity. Nature Med. 11, 199–205 (2005).

    CAS  PubMed  Google Scholar 

  41. 41

    Cohen, P. et al. Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science 297, 240–243 (2002).

    CAS  PubMed  Google Scholar 

  42. 42

    Watson, R. T. & Pessin, J. E. Intracellular organization of insulin signaling and GLUT4 translocation. Recent Prog. Horm. Res. 56, 175–193 (2001).

    CAS  PubMed  Google Scholar 

  43. 43

    Roden, M. et al. Mechanism of free fatty acid-induced insulin resistance in humans. J. Clin. Invest 97, 2859–2865 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Anderson, R. G. Joe Goldstein and Mike Brown: from cholesterol homeostasis to new paradigms in membrane biology. Trends Cell Biol. 13, 534–539 (2003).

    CAS  PubMed  Google Scholar 

  45. 45

    Rawson, R. B. The SREBP pathway — insights from Insigs and insects. Nature Rev. Mol. Cell Biol. 4, 631–640 (2003).

    CAS  Google Scholar 

  46. 46

    Watkins, S. M., Reifsnyder, P. R., Pan, H. J., German, J. B. & Leiter, E. H. Lipid metabolome-wide effects of the PPARgamma agonist rosiglitazone. J. Lipid Res. 43, 1809–1817 (2002).

    CAS  PubMed  Google Scholar 

  47. 47

    Santagata, S. et al. G-protein signaling through tubby proteins. Science 292, 2041–2050 (2001). Study which shows, based in structural analysis, that tubby proteins bind to phosphoinositides and that cellular stimulation leads to release of tubby from the membrane.

    CAS  PubMed  Google Scholar 

  48. 48

    Carroll, K., Gomez, C. & Shapiro, L. Tubby proteins: the plot thickens. Nature Rev. Mol. Cell Biol. 5, 55–63 (2004).

    CAS  Google Scholar 

  49. 49

    Auger, K. R., Serunian, L. A., Soltoff, S. P., Libby, P. & Cantley, L. C. PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells. Cell 57, 167–175 (1989).

    CAS  PubMed  Google Scholar 

  50. 50

    Czech, M. P. Dynamics of phosphoinositides in membrane retrieval and insertion. Annu. Rev. Physiol. 65, 791–815 (2003).

    CAS  Google Scholar 

  51. 51

    Maehama, T. & Dixon, J. E. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3, 4, 5-trisphosphate. J. Biol. Chem. 273, 13375–13378 (1998).

    CAS  Google Scholar 

  52. 52

    Pendaries, C., Tronchere, H., Plantavid, M. & Payrastre, B. Phosphoinositide signaling disorders in human diseases. FEBS Lett. 546, 25–31 (2003).

    CAS  PubMed  Google Scholar 

  53. 53

    Giannakou, M. E. et al. Long-lived Drosophila with overexpressed dFOXO in adult fat body. Science 305, 361 (2004).

    CAS  PubMed  Google Scholar 

  54. 54

    Finan, P. M. & Thomas, M. J. PI 3-kinase inhibition: a therapeutic target for respiratory disease. Biochem. Soc. Trans. 32, 378–382 (2004). Review article which summarizes recent advances in therapeutic targeting of PI-3 kinases

    CAS  PubMed  Google Scholar 

  55. 55

    Fruman, D. A. Towards an understanding of isoform specificity in phosphoinositide 3-kinase signalling in lymphocytes. Biochem. Soc. Trans. 32, 315–319 (2004).

    CAS  PubMed  Google Scholar 

  56. 56

    Schmid, A. C. & Woscholski, R. Phosphatases as small-molecule targets: inhibiting the endogenous inhibitors of kinases. Biochem. Soc. Trans. 32, 348–349 (2004).

    CAS  PubMed  Google Scholar 

  57. 57

    Wetzker, R. & Rommel, C. Phosphoinositide 3-kinases as targets for therapeutic intervention. Curr. Pharm. Des 10, 1915–1922 (2004).

    CAS  PubMed  Google Scholar 

  58. 58

    Heinrich, M. et al. Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and-3 activation. Cell Death. Differ. 11, 550–563 (2004).

    CAS  PubMed  Google Scholar 

  59. 59

    Bose, R. et al. Ceramide synthase mediates daunorubicin-induced apoptosis: an alternative mechanism for generating death signals. Cell 82, 405–414 (1995).

    CAS  PubMed  Google Scholar 

  60. 60

    Ogretmen, B. & Hannun, Y. A. Biologically active sphingolipids in cancer pathogenesis and treatment. Nature Rev. Cancer 4, 604–616 (2004).

    CAS  Google Scholar 

  61. 61

    Xia, P. et al. An oncogenic role of sphingosine kinase. Curr. Biol. 10, 1527–1530 (2000).

    CAS  Google Scholar 

  62. 62

    Liu, F. et al. Differential regulation of sphingosine-1-phosphate- and VEGF-induced endothelial cell chemotaxis. Involvement of G(ialpha2)-linked Rho kinase activity. Am. J. Respir. Cell Mol. Biol. 24, 711–719 (2001).

    CAS  Google Scholar 

  63. 63

    Corda, D., Iurisci, C. & Berrie, C. P. Biological activities and metabolism of the lysophosphoinositides and glycerophosphoinositols. Biochim. Biophys. Acta 1582, 52–69 (2002).

    CAS  PubMed  Google Scholar 

  64. 64

    Hideshima, T. et al. Antitumor activity of lysophosphatidic acid acyltransferase-beta inhibitors, a novel class of agents, in multiple myeloma. Cancer Res. 63, 8428–8436 (2003).

    CAS  PubMed  Google Scholar 

  65. 65

    Basler, J. W. & Piazza, G. A. Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 selective inhibitors for prostate cancer chemoprevention. J. Urol. 171, S59–S62 (2004).

    CAS  PubMed  Google Scholar 

  66. 66

    Cremona, O. & De Camilli, P. Phosphoinositides in membrane traffic at the synapse. J. Cell. Sci. 114, 1041–1052 (2001).

    CAS  PubMed  Google Scholar 

  67. 67

    Cutler, R. G. et al. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. Proc. Natl Acad. Sci. USA 101, 2070–2075 (2004).

    CAS  PubMed  Google Scholar 

  68. 68

    Yanagisawa, K., Odaka, A., Suzuki, N. & Ihara, Y. GM1 ganglioside-bound amyloid beta-protein (A beta): a possible form of preamyloid in Alzheimer's disease. Nature Med. 1, 1062–1066 (1995).

    CAS  PubMed  Google Scholar 

  69. 69

    Perrin, R. J., Woods, W. S., Clayton, D. F. & George, J. M. Exposure to long chain polyunsaturated fatty acids triggers rapid multimerization of synucleins. J. Biol. Chem. 276, 41958–41962 (2001).

    CAS  PubMed  Google Scholar 

  70. 70

    Sharon, R. et al. The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson's disease. Neuron 37, 583–595 (2003).

    CAS  PubMed  Google Scholar 

  71. 71

    Lwin, A., Orvisky, E., Goker-Alpan, O., LaMarca, M. E. & Sidransky, E. Glucocerebrosidase mutations in subjects with parkinsonism. Mol. Genet. Metab 81, 70–73 (2004).

    CAS  PubMed  Google Scholar 

  72. 72

    Pentchev, P. G. et al. A defect in cholesterol esterification in Niemann–Pick disease (type C) patients. Proc. Natl Acad. Sci. USA 82, 8247–8251 (1985).

    CAS  PubMed  Google Scholar 

  73. 73

    Sturley, S. L., Patterson, M. C., Balch, W. & Liscum, L. The pathophysiology and mechanisms of NP-C disease. Biochim. Biophys. Acta 1685, 83–87 (2004).

    CAS  PubMed  Google Scholar 

  74. 74

    Selkoe, D. J. Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's diseases. Nature Cell Biol. 6, 1054–1061 (2004).

    CAS  PubMed  Google Scholar 

  75. 75

    Stebbins, C. E. & Galan, J. E. Structural mimicry in bacterial virulence. Nature 412, 701–705 (2001).

    CAS  PubMed  Google Scholar 

  76. 76

    Walburger, A. et al. Protein kinase G from pathogenic mycobacteria promotes survival within macrophages. Science 304, 1800–1804 (2004).

    CAS  PubMed  Google Scholar 

  77. 77

    Poltorak, A. et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085–2088 (1998).

    CAS  Google Scholar 

  78. 78

    Akira, S. & Takeda, K. Toll-like receptor signalling. Nature Rev. Immunol. 4, 499–511 (2004).

    CAS  Google Scholar 

  79. 79

    Jahn, R., Lang, T. & Sudhof, T. C. Membrane fusion. Cell 112, 519–533 (2003).

    CAS  Google Scholar 

  80. 80

    Simons, K. & Ikonen, E. Functional rafts in cell membranes. Nature 387, 569–572 (1997).

    CAS  Google Scholar 

  81. 81

    Kobayashi, T. et al. A lipid associated with the antiphospholipid syndrome regulates endosome structure and function. Nature 392, 193–197 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82

    Anderson, R. G. & Jacobson, K. A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains. Science 296, 1821–1825 (2002).

    CAS  Google Scholar 

  83. 83

    Gatfield, J. & Pieters, J. Essential role for cholesterol in entry of mycobacteria into macrophages. Science 288, 1647–1650 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84

    Ono, A., Ablan, S. D., Lockett, S. J., Nagashima, K. & Freed, E. O. Phosphatidylinositol (4, 5) bisphosphate regulates HIV-1 Gag targeting to the plasma membrane. Proc. Natl Acad. Sci. USA 101, 14889–14894 (2004).

    CAS  PubMed  Google Scholar 

  85. 85

    Lindwasser, O. W. & Resh, M. D. Multimerization of human immunodeficiency virus type 1 Gag promotes its localization to barges, raft-like membrane microdomains. J. Virol. 75, 7913–7924 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. 86

    Nguyen, D. H. & Hildreth, J. E. Evidence for budding of human immunodeficiency virus type 1 selectively from glycolipid-enriched membrane lipid rafts. J. Virol. 74, 3264–3272 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. 87

    Finnegan, C. M. et al. Ceramide, a target for antiretroviral therapy. Proc. Natl Acad. Sci. USA 101, 15452–15457 (2004).

    CAS  PubMed  Google Scholar 

  88. 88

    Scheiffele, P., Rietveld, A., Wilk, T. & Simons, K. Influenza viruses select ordered lipid domains during budding from the plasma membrane. J. Biol. Chem. 274, 2038–2044 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. 89

    Campbell, S. M., Crowe, S. M. & Mak, J. Virion-associated cholesterol is critical for the maintenance of HIV-1 structure and infectivity. AIDS 16, 2253–2261 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. 90

    Morris-Natschke, S. L., Ishaq, K. S. & Kucera, L. S. Phospholipid analogs against HIV-1 infection and disease. Curr. Pharm. Des. 9, 1441–1451 (2003).

    CAS  PubMed  Google Scholar 

  91. 91

    Raulin, J. Human immunodeficiency virus and host cell lipids. Interesting pathways in research for a new HIV therapy. Prog. Lipid. Res. 41, 27–65 (2002).

    CAS  PubMed  Google Scholar 

  92. 92

    Vergne, I., Chua, J. & Deretic, V. Tuberculosis toxin blocking phagosome maturation inhibits a novel Ca2+/calmodulin-PI3K hVPS34 cascade. J. Exp. Med. 198, 653–659 (2003).

    PubMed  PubMed Central  Google Scholar 

  93. 93

    Rhoades, E. et al. Identification and macrophage-activating activity of glycolipids released from intracellular Mycobacterium bovis BCG. Mol. Microbiol. 48, 875–888 (2003).

    CAS  PubMed  Google Scholar 

  94. 94

    Fratti, R. A., Chua, J., Vergne, I. & Deretic, V. Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest. Proc. Natl Acad. Sci. USA 100, 5437–5442 (2003).

    CAS  PubMed  Google Scholar 

  95. 95

    Hernandez, L. D., Hueffer, K., Wenk, M. R. & Galan, J. E. Salmonella modulates vesicular traffic by altering phosphoinositide metabolism. Science 304, 1805–1807 (2004).

    CAS  PubMed  Google Scholar 

  96. 96

    Converse, S. E. et al. MmpL8 is required for sulfolipid-1 biosynthesis and Mycobacterium tuberculosis virulence. Proc. Natl Acad. Sci. USA 100, 6121–6126 (2003).

    CAS  PubMed  Google Scholar 

  97. 97

    Thompson, C. R. et al. Sphingosine kinase 1 (SK1) is recruited to nascent phagosomes in human macrophages: inhibition of SK1 translocation by Mycobacterium tuberculosis. J. Immunol. 174, 3551–3561 (2005).

    CAS  PubMed  Google Scholar 

  98. 98

    Mota, L. J., Journet, L., Sorg, I., Agrain, C. & Cornelis, G. R. Bacterial injectisomes: needle length does matter. Science 307, 1278 (2005).

    PubMed  Google Scholar 

  99. 99

    Vergne, I. et al. Mechanism of phagolysosome biogenesis block by viable Mycobacterium tuberculosis. Proc. Natl Acad. Sci. USA 102, 4033–4038 (2005).

    CAS  PubMed  Google Scholar 

  100. 100

    Steele-Mortimer, O. et al. Activation of Akt/protein kinase B in epithelial cells by the Salmonella typhimurium effector sigD. J. Biol. Chem. 275, 37718–37724 (2000).

    CAS  PubMed  Google Scholar 

  101. 101

    Porcelli, S. et al. Recognition of cluster of differentiation 1 antigens by human CD4-CD8-cytolytic T lymphocytes. Nature 341, 447–450 (1989).

    CAS  Google Scholar 

  102. 102

    Sieling, P. A. et al. CD1-restricted T cell recognition of microbial lipoglycan antigens. Science 269, 227–230 (1995).

    CAS  Google Scholar 

  103. 103

    Brigl, M. & Brenner, M. B. CD1: Antigen presentation and T cell function. Annu. Rev. Immunol. 22, 817–890 (2004).

    CAS  Google Scholar 

  104. 104

    Hava, D. L. et al. CD1 assembly and the formation of CD1-antigen complexes. Curr. Opin. Immunol. 17, 88–94 (2005).

    CAS  PubMed  Google Scholar 

  105. 105

    Winau, F. et al. Saposin C is required for lipid presentation by human CD1b. Nature Immunol. 5, 169–174 (2004).

    CAS  Google Scholar 

  106. 106

    Park, J. J. et al. Lipid-protein interactions: biosynthetic assembly of CD1 with lipids in the endoplasmic reticulum is evolutionarily conserved. Proc. Natl Acad. Sci. USA 101, 1022–1026 (2004).

    CAS  PubMed  Google Scholar 

  107. 107

    Han, X. & Gross, R. W. Electrospray ionization mass spectroscopic analysis of human erythrocyte plasma membrane phospholipids. Proc. Natl Acad. Sci. USA 91, 10635–10639 (1994).

    CAS  PubMed  Google Scholar 

  108. 108

    Kim, H. Y., Wang, T. C. & Ma, Y. C. Liquid chromatography/mass spectrometry of phospholipids using electrospray ionization. Anal. Chem. 66, 3977–3982 (1994).

    CAS  PubMed  Google Scholar 

  109. 109

    Kerwin, J. L., Tuininga, A. R. & Ericsson, L. H. Identification of molecular species of glycerophospholipids and sphingomyelin using electrospray mass spectrometry. J. Lipid. Res. 35, 1102–1114 (1994).

    CAS  PubMed  Google Scholar 

  110. 110

    Pulfer, M. & Murphy, R. C. Electrospray mass spectrometry of phospholipids. Mass Spectrom. Rev. 22, 332–364 (2003). Excellent methodological overview of LC and MS based approaches for lipid analysis.

    CAS  PubMed  Google Scholar 

  111. 111

    Han, X. & Gross, R. W. Global analyses of cellular lipidomes directly from crude extracts of biological samples by ESI/MS: a bridge to lipidomics. J. Lipid. Res. 44, 1071–1079 (2003).

    CAS  PubMed  Google Scholar 

  112. 112

    Welti, R. & Wang, X. Lipid species profiling: a high-throughput approach to identify lipid compositional changes and determine the function of genes involved in lipid metabolism and signaling. Curr. Opin. Plant Biol. 7, 337–344 (2004).

    CAS  PubMed  Google Scholar 

  113. 113

    Brugger, B., Erben, G., Sandhoff, R., Wieland, F. T. & Lehmann, W. D. Quantitative analysis of biological membrane lipids at the low picomole level by nano-electrospray ionization tandem mass spectrometry. Proc. Natl Acad. Sci. USA 94, 2339–2344 (1997). Landmark publication demonstrating substantially improved sensitivity for analysis of phospholipids in complex mixtures based on nanoflow ESI MS.

    CAS  PubMed  Google Scholar 

  114. 114

    Sullards, M. C. & Merrill, A. H., Jr. Analysis of sphingosine 1-phosphate, ceramides, and other bioactive sphingolipids by high-performance liquid chromatography-tandem mass spectrometry. Sci STKE PL1 (2001).

  115. 115

    Han, X. & Gross, R. W. Quantitative analysis and molecular species fingerprinting of triacylglyceride molecular species directly from lipid extracts of biological samples by electrospray ionization tandem mass spectrometry. Anal. Biochem. 295, 88–100 (2001).

    CAS  PubMed  Google Scholar 

  116. 116

    Ivanova, P. T. et al. Electrospray ionization mass spectrometry analysis of changes in phospholipids in RBL-2H3 mastocytoma cells during degranulation. Proc. Natl Acad. Sci. USA 98, 7152–7157 (2001).

    CAS  PubMed  Google Scholar 

  117. 117

    Han, X., Yang, J., Cheng, H., Ye, H. & Gross, R. W. Toward fingerprinting cellular lipidomes directly from biological samples by two-dimensional electrospray ionization mass spectrometry. Anal. Biochem. 330, 317–331 (2004).

    CAS  PubMed  Google Scholar 

  118. 118

    Ekroos, K., Chernushevich, I. V., Simons, K. & Shevchenko, A. Quantitative profiling of phospholipids by multiple precursor ion scanning on a hybrid quadrupole time-of-flight mass spectrometer. Anal. Chem. 74, 941–949 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. 119

    Schaub, T. M., Hendrickson, C. L., Qian, K., Quinn, J. P. & Marshall, A. G. High-resolution field desorption/ionization fourier transform ion cyclotron resonance mass analysis of nonpolar molecules. Anal. Chem. 75, 2172–2176 (2003).

    CAS  PubMed  Google Scholar 

  120. 120

    Wenk, M. R. et al. Phosphoinositide profiling in complex lipid mixtures using electrospray ionization mass spectrometry. Nature Biotechnol. 21, 813–817 (2003).

    CAS  Google Scholar 

  121. 121

    Han, X. Characterization and direct quantitation of ceramide molecular species from lipid extracts of biological samples by electrospray ionization tandem mass spectrometry. Anal. Biochem. 302, 199–212 (2002).

    CAS  PubMed  Google Scholar 

  122. 122

    Ivleva, V. B. et al. Coupling thin-layer chromatography with vibrational cooling matrix-assisted laser desorption/ionization Fourier transform mass spectrometry for the analysis of ganglioside mixtures. Anal. Chem. 76, 6484–6491 (2004).

    CAS  PubMed  Google Scholar 

  123. 123

    Welti, R. et al. Profiling membrane lipids in plant stress responses. Role of phospholipase D alpha in freezing-induced lipid changes in Arabidopsis. J. Biol. Chem. 277, 31994–32002 (2002).

    CAS  Google Scholar 

  124. 124

    Koivusalo, M., Haimi, P., Heikinheimo, L., Kostiainen, R. & Somerharju, P. Quantitative determination of phospholipid compositions by ESI-MS: effects of acyl chain length, unsaturation, and lipid concentration on instrument response. J. Lipid. Res. 42, 663–672 (2001).

    PubMed  Google Scholar 

  125. 125

    Petkovic, M. et al. Detection of individual phospholipids in lipid mixtures by matrix- assisted laser desorption/ionization time-of-flight mass spectrometry: phosphatidylcholine prevents the detection of further species. Anal. Biochem. 289, 202–216 (2001).

    CAS  PubMed  Google Scholar 

  126. 126

    Muller, M. et al. Limits for the detection of (poly-)phosphoinositides by matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI- TOF MS). Chem. Phys. Lipids 110, 151–164 (2001).

    CAS  PubMed  Google Scholar 

  127. 127

    Houjou, T., Yamatani, K., Imagawa, M., Shimizu, T. & Taguchi, R. A shotgun tandem mass spectrometric analysis of phospholipids with normal-phase and/or reverse-phase liquid chromatography/electrospray ionization mass spectrometry. Rapid Commun. Mass Spectrom. 19, 654–666 (2005).

    CAS  PubMed  Google Scholar 

  128. 128

    Hermansson, M., Uphoff, A., Kakela, R. & Somerharju, P. Automated quantitative analysis of complex lipidomes by liquid chromatography/mass spectrometry. Anal. Chem. 77, 2166–2175 (2005).

    CAS  PubMed  Google Scholar 

  129. 129

    Watkins, S. M. Lipomic profiling in drug discovery, development and clinical trial evaluation. Curr. Opin. Drug Discov. Devel. 7, 112–117 (2004).

    CAS  PubMed  Google Scholar 

  130. 130

    Picchioni, G. A., Watada, A. E. & Whitaker, B. D. Quantitative high-performance liquid chromatography analysis of plant phospholipids and glycolipids using light-scattering detection. Lipids 31, 217–221 (1996).

    CAS  PubMed  Google Scholar 

  131. 131

    Nasuhoglu, C. et al. Nonradioactive analysis of phosphatidylinositides and other anionic phospholipids by anion-exchange high-performance liquid chromatography with suppressed conductivity detection. Anal. Biochem. 301, 243–254 (2002).

    CAS  PubMed  Google Scholar 

  132. 132

    Lin, S., Fischl, A. S., Bi, X. & Parce, W. Separation of phospholipids in microfluidic chip device: application to high-throughput screening assays for lipid-modifying enzymes. Anal. Biochem. 314, 97–107 (2003).

    CAS  PubMed  Google Scholar 

  133. 133

    Qi, L., Danielson, N. D., Dai, Q. & Lee, R. M. Capillary electrophoresis of cardiolipin with on-line dye interaction and spectrophotometric detection. Electrophoresis 24, 1680–1686 (2003).

    CAS  PubMed  Google Scholar 

  134. 134

    German, J. B., Roberts, M. A. & Watkins, S. M. Personal metabolomics as a next generation nutritional assessment. J. Nutr. 133, 4260–4266 (2003).

    CAS  PubMed  Google Scholar 

  135. 135

    Adams, A. & Kingsbury, J. Lipomic profiling, profiled. Modern Drug Discov. 55–56 (2004).

  136. 136

    Seelig, A. & Seelig, J. Effect of a single cis double bond on the structures of a phospholipid bilayer. Biochemistry 16, 45–50 (1977).

    CAS  PubMed  Google Scholar 

  137. 137

    Gawrisch, K., Eldho, N. V. & Polozov, I. V. Novel NMR tools to study structure and dynamics of biomembranes. Chem. Phys. Lipids 116, 135–151 (2002).

    CAS  PubMed  Google Scholar 

  138. 138

    Marsh, D. & Pali, T. The protein-lipid interface: perspectives from magnetic resonance and crystal structures. Biochim. Biophys. Acta 1666, 118–141 (2004).

    CAS  PubMed  Google Scholar 

  139. 139

    Marsh, D. & Barrantes, F. J. Immobilized lipid in acetylcholine receptor-rich membranes from Torpedo marmorata. Proc. Natl Acad. Sci. USA 75, 4329–4333 (1978).

    CAS  PubMed  Google Scholar 

  140. 140

    Hilgemann, D. W., Feng, S. & Nasuhoglu, C. The complex and intriguing lives of PIP2 with ion channels and transporters. Sci. STKE. RE19 (2001).

  141. 141

    Fu, R. & Cross, T. A. Solid-state nuclear magnetic resonance investigation of protein and polypeptide structure. Annu. Rev. Biophys. Biomol. Struct. 28, 235–268 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. 142

    Gavaghan, C. L., Holmes, E., Lenz, E., Wilson, I. D. & Nicholson, J. K. An NMR-based metabonomic approach to investigate the biochemical consequences of genetic strain differences: application to the C57BL10J and Alpk:ApfCD mouse. FEBS Lett. 484, 169–174 (2000).

    CAS  PubMed  Google Scholar 

  143. 143

    Nicholson, J. K. & Wilson, I. D. Opinion: understanding 'global' systems biology: metabonomics and the continuum of metabolism. Nature Rev. Drug Discov. 2, 668–676 (2003).

    CAS  Google Scholar 

  144. 144

    Prestwich, G. D. Phosphoinositide signaling; from affinity probes to pharmaceutical targets. Chem. Biol. 11, 619–637 (2004).

    CAS  PubMed  Google Scholar 

  145. 145

    Taylor, G. S. & Dixon, J. E. Assaying phosphoinositide phosphatases. Methods Mol. Biol. 284, 217–228 (2004).

    CAS  PubMed  Google Scholar 

  146. 146

    Zhu, H. et al. Global analysis of protein activities using proteome chips. Science 293, 2101–2105 (2001). Identification of lipid binding proteins using arrays of immobilized protein.

    CAS  Google Scholar 

  147. 147

    Mukherjee, S. & Maxfield, F. R. Role of membrane organization and membrane domains in endocytic lipid trafficking. Traffic 1, 203–211 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. 148

    Kol, M. A., de Kroon, A. I., Killian, J. A. & de, K. B. Transbilayer movement of phospholipids in biogenic membranes. Biochemistry 43, 2673–2681 (2004).

    CAS  PubMed  Google Scholar 

  149. 149

    Wenk, M. R. & De Camilli, P. Assembly of endocytosis-associated proteins on liposomes. Meth. Enzymol. 372, 248–260 (2003).

    CAS  PubMed  Google Scholar 

  150. 150

    Krugmann, S. et al. Identification of ARAP3, a novel PI3K effector regulating both Arf and Rho GTPases, by selective capture on phosphoinositide affinity matrices. Mol. Cell 9, 95–108 (2002). Biochemical work based on affinity chromatography using immobilized lipids as baits for the identification of novel lipid binding proteins.

    CAS  PubMed  Google Scholar 

  151. 151

    Kolusheva, S., Boyer, L. & Jelinek, R. A colorimetric assay for rapid screening of antimicrobial peptides. Nature Biotechnol. 18, 225–227 (2000).

    CAS  Google Scholar 

  152. 152

    Botelho, R. J. et al. Localized biphasic changes in phosphatidylinositol-4, 5-bisphosphate at sites of phagocytosis. J. Cell Biol. 151, 1353–1368 (2000). Elegant cell biological study, using fluorescent methods, of phosphoinositide and DG metabolism during phagocytosis.

    CAS  PubMed  PubMed Central  Google Scholar 

  153. 153

    Bligh, E. G. & Dyer, W. J. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37, 911–917 (1959).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. 154

    Folch, J., Ascoli, I., Lees, M., Meath, J. A. & Le, B. N. Preparation of lipide extracts from brain tissue. J. Biol. Chem. 191, 833–841 (1951).

    CAS  PubMed  Google Scholar 

  155. 155

    Wenk, M. R. & De Camilli, P. in Functional Lipidomics (eds. Feng, L. & Prestwich, G. D.) (Dekker-CRC, New York, in the press).

  156. 156

    Fahy, E. et al. A comprehensive classification system for lipids. J. Lipid Res. 46, 839–862 (2005). Comprehensive classification scheme for lipids which will help facilitate exchange of information and databasing of large amounts of lipidomic data.

    CAS  PubMed  PubMed Central  Google Scholar 

  157. 157

    Forrester, J. S., Milne, S. B., Ivanova, P. T. & Brown, H. A. Computational lipidomics: a multiplexed analysis of dynamic changes in membrane lipid composition during signal transduction. Mol. Pharmacol. 65, 813–821 (2004).

    CAS  PubMed  Google Scholar 

  158. 158

    Lu, Y., Hong, S., Tjonahen, E. & Serhan, C. N. Mediator-lipidomics: databases and search algorithms for PUFA-derived mediators. J. Lipid Res. 46, 790–802 (2005). Novel algorithms and databases for the identification of lipid mediators based on mass spectrometry and UV spectroscopy.

    CAS  PubMed  Google Scholar 

  159. 159

    varez-Vasquez, F. et al. Simulation and validation of modelled sphingolipid metabolism in Saccharomyces cerevisiae. Nature 433, 425–430 (2005).

    Google Scholar 

  160. 160

    Vance, D. E. & Vance, J. E. (eds) Biochemistry of Lipids, Lipoproteins and Membranes (Elsevier, New York, 2001).

    Google Scholar 

  161. 161

    Lemmon, M. A. Pleckstrin homology domains: not just for phosphoinositides. Biochem. Soc. Trans. 32, 707–711 (2004).

    CAS  PubMed  Google Scholar 

  162. 162

    Weckwerth, W., Loureiro, M. E., Wenzel, K. & Fiehn, O. Differential metabolic networks unravel the effects of silent plant phenotypes. Proc. Natl Acad. Sci. USA 101, 7809–7814 (2004).

    CAS  PubMed  Google Scholar 

  163. 163

    Cascante, M. et al. Metabolic control analysis in drug discovery and disease. Nature Biotechnol. 20, 243–249 (2002).

    CAS  Google Scholar 

  164. 164

    Hodgkin, M. N. et al. Diacylglycerols and phosphatidates: which molecular species are intracellular messengers? Trends Biochem. Sci. 23, 200–204 (1998).

    CAS  PubMed  Google Scholar 

  165. 165

    Gronert, K. et al. A molecular defect in intracellular lipid signaling in human neutrophils in localized aggressive periodontal tissue damage. J. Immunol. 172, 1856–1861 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  166. 166

    Kroesen, B. J. et al. Induction of apoptosis through B-cell receptor cross-linking occurs via de novo generated C16-ceramide and involves mitochondria. J. Biol. Chem. 276, 13606–13614 (2001).

    CAS  Google Scholar 

  167. 167

    Koybasi, S. et al. Defects in cell growth regulation by C18:0-ceramide and longevity assurance gene 1 in human head and neck squamous cell carcinomas. J. Biol. Chem. 279, 44311–44319 (2004).

    CAS  PubMed  Google Scholar 

  168. 168

    Alaimo, P. J., Shogren-Knaak, M. A. & Shokat, K. M. Chemical genetic approaches for the elucidation of signaling pathways. Curr. Opin. Chem. Biol. 5, 360–367 (2001).

    CAS  PubMed  Google Scholar 

  169. 169

    Zewail, A. et al. Novel functions of the phosphatidylinositol metabolic pathway discovered by a chemical genomics screen with wortmannin. Proc. Natl Acad. Sci. USA 100, 3345–3350 (2003). Chemogenetic screen using yeast knock-out libraries and a kinase inhibitor.

    CAS  PubMed  Google Scholar 

  170. 170

    Boshoff, H. I. et al. The transcriptional responses of Mycobacterium tuberculosis to inhibitors of metabolism: novel insights into drug mechanisms of action. J. Biol. Chem. 279, 40174–40184 (2004).

    CAS  PubMed  Google Scholar 

  171. 171

    Moody, D. B. et al. T cell activation by lipopeptide antigens. Science 303, 527–531 (2004). Recent report in a series of papers which demonstrates that CD1a receptor present lipid molecules (a lipopetide in this case) during T cell activation.

    CAS  PubMed  Google Scholar 

  172. 172

    Hoebe, K. et al. CD36 is a sensor of diacylglycerides. Nature 433, 523–527 (2005).

    CAS  PubMed  Google Scholar 

  173. 173

    Matsuda, L. A., Lolait, S. J., Brownstein, M. J., Young, A. C. & Bonner, T. I. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346, 561–564 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  174. 174

    Devane, W. A. et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258, 1946–1949 (1992). Discovery based on biochemical binding experiment and analytical chemistry of an endogenous ligand, anandamide, for the cannabinoid receptor

    CAS  PubMed  PubMed Central  Google Scholar 

  175. 175

    McFarland, M. J. & Barker, E. L. Anandamide transport. Pharmacol. Ther. 104, 117–135 (2004).

    CAS  PubMed  Google Scholar 

  176. 176

    Hamman, B. D., Pollok, B. A., Bennett, T., Allen, J. & Heim, R. Binding of a Pleckstrin homology domain protein to phosphoinositide in membranes: a miniaturized FRET-based assay for drug screening. J. Biomol. Screen. 7, 45–55 (2002).

    CAS  PubMed  Google Scholar 

  177. 177

    Gray, A., Olsson, H., Batty, I. H., Priganica, L. & Peter Downes, C. Nonradioactive methods for the assay of phosphoinositide 3-kinases and phosphoinositide phosphatases and selective detection of signaling lipids in cell and tissue extracts. Anal. Biochem. 313, 234–245 (2003).

    CAS  PubMed  Google Scholar 

  178. 178

    Saghatelian, A. et al. Assignment of endogenous substrates to enzymes by global metabolite profiling. Biochemistry 43, 14332–14339 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  179. 179

    Cicchetti, G., Biernacki, M., Farquharson, J. & Allen, P. G. A ratiometric expressible FRET sensor for phosphoinositides displays a signal change in highly dynamic membrane structures in fibroblasts. Biochemistry 43, 1939–1949 (2004).

    CAS  PubMed  Google Scholar 

  180. 180

    Tanimura, A., Nezu, A., Morita, T., Turner, R. J. & Tojyo, Y. Fluorescent biosensor for quantitative real-time measurements of inositol 1, 4, 5-trisphosphate in single living cells. J. Biol. Chem. 279, 38095–38098 (2004).

    CAS  PubMed  Google Scholar 

  181. 181

    Nieland, T. J. et al. Chemical genetic screening identifies sulfonamides that raise organellar pH and interfere with membrane traffic. Traffic. 5, 478–492 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  182. 182

    Rudolf, M. T., Dinkel, C., Traynor-Kaplan, A. E. & Schultz, C. Antagonists of myo-inositol 3, 4, 5, 6-tetrakisphosphate allow repeated epithelial chloride secretion. Bioorg. Med. Chem. 11, 3315–3329 (2003).

    CAS  PubMed  Google Scholar 

  183. 183

    Saiardi, A., Bhandari, R., Resnick, A. C., Snowman, A. M. & Snyder, S. H. Phosphorylation of proteins by inositol pyrophosphates. Science 306, 2101–2105 (2004).

    CAS  PubMed  Google Scholar 

  184. 184

    Andresen, T. L., Davidsen, J., Begtrup, M., Mouritsen, O. G. & Jorgensen, K. Enzymatic release of antitumor ether lipids by specific phospholipase A2 activation of liposome-forming prodrugs. J. Med. Chem. 47, 1694–1703 (2004).

    CAS  PubMed  Google Scholar 

  185. 185

    Chithalen, J. V., Luu, L., Petkovich, M. & Jones, G. HPLC-MS/MS analysis of the products generated from all-trans-retinoic acid using recombinant human CYP26A. J. Lipid Res. 43, 1133–1142 (2002).

    CAS  PubMed  Google Scholar 

  186. 186

    Robertson, D. G. Metabonomics in toxicology: a review. Toxicol. Sci. 85, 809–822 (2005).

    CAS  PubMed  Google Scholar 

  187. 187

    Butterfield, D. A. Amyloid beta-peptide (1–42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer's disease brain. A review. Free Radic. Res. 36, 1307–1313 (2002).

    CAS  PubMed  Google Scholar 

  188. 188

    Montine, K. S. et al. Isoprostanes and related products of lipid peroxidation in neurodegenerative diseases. Chem. Phys. Lipids 128, 117–124 (2004).

    CAS  PubMed  Google Scholar 

  189. 189

    Basu, S., Whiteman, M., Mattey, D. L. & Halliwell, B. Raised levels of F(2)-isoprostanes and prostaglandin F(2alpha) in different rheumatic diseases. Ann. Rheum. Dis. 60, 627–631 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  190. 190

    Spickett, C. M., Pitt, A. R. & Brown, A. J. Direct observation of lipid hydroperoxides in phospholipid vesicles by electrospray mass spectrometry. Free Radic. Biol. Med. 25, 613–620 (1998).

    CAS  PubMed  Google Scholar 

  191. 191

    Ishida, M. et al. High-resolution analysis by nano-electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry for the identification of molecular species of phospholipids and their oxidized metabolites. Rapid Commun. Mass Spectrom. 18, 2486–2494 (2004).

    CAS  PubMed  Google Scholar 

  192. 192

    Leitinger, N. et al. Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils. Proc. Natl Acad. Sci. USA 96, 12010–12015 (1999).

    CAS  PubMed  Google Scholar 

  193. 193

    Lutter, M. et al. Cardiolipin provides specificity for targeting of tBid to mitochondria. Nature Cell Biol. 2, 754–761 (2000).

    CAS  PubMed  Google Scholar 

  194. 194

    Kagan, V. E. et al. A role for oxidative stress in apoptosis: oxidation and externalization of phosphatidylserine is required for macrophage clearance of cells undergoing Fas-mediated apoptosis. J. Immunol. 169, 487–499 (2002).

    CAS  Google Scholar 

  195. 195

    Bannenberg, G. L. et al. Molecular circuits of resolution: formation and actions of resolvins and protectins. J. Immunol. 174, 4345–4355 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  196. 196

    Pravdova, V., Walczak, B. & Massart, D. L. A comparison of two algorithms for warping of analytical signals. Anal. Chim. Acta 456, 77–92 (2002).

    CAS  Google Scholar 

  197. 197

    Weckwerth, W. Metabolomics in systems biology. Annu. Rev. Plant Physiol. Plant Mol. Biol. 54, 669–689 (2003).

    CAS  Google Scholar 

  198. 198

    McLaughlin, S., Wang, J., Gambhir, A. & Murray, D. PIP(2) and proteins: interactions, organization, and information flow. Annu. Rev. Biophys. Biomol. Struct. 31, 151–175 (2002).

    CAS  Google Scholar 

  199. 199

    Barrantes, F. J. Structural basis for lipid modulation of nicotinic acetylcholine receptor function. Brain Res. Brain Res. Rev. 47, 71–95 (2004).

    CAS  PubMed  Google Scholar 

  200. 200

    Lemmon, M. A. Phosphoinositide recognition domains. Traffic 4, 201–213 (2003).

    CAS  PubMed  Google Scholar 

Download references


I would like to thank all members of our group and those of the labs of G. Di Paolo, M. Kemeny and U.-A. Boelsterli, as well as the external reviewers for their constructive comments. Work in our laboratory is supported by research grants from the National University of Singapore, the National Medical Research Council of Singapore and the Novartis Institutes for Tropical Research.

Author information



Ethics declarations

Competing interests

The author declares no competing financial interests.

Related links

Related links


Entrez Gene

Cathepsin D

CB1 cannabinoid receptor




PI3 kinase






Alzheimer's disease

early-onset Parkinson's disease

multiple myeloma

Niemann–Pick disease type C

Parkinson's disease



Alliance for Cell Signalling

Cyber Lipid Center

European Lipidomics Initiative

Kansas Lipodomics Research Center


Lipid Bank

Lipid Library – All About Lipids

Lipid MAPS


Lipid Profiles

MUSC Lipodomics Core Facility



Systems-level analysis and characterization of lipids and their interacting moieties.


A discipline that aims at deciphering relationships between different parts of a biological system (for example, a metabolic chain, cell or tissue) with the goal of understanding (and predicting) the behaviour of the system as a whole.


Enzymatic catalysis at an interface, such as the surface of a biological membrane.


Pleckstrin homology domain. A widespread and functionally diverse protein fold that mediates intermolecular interactions, most notably with phosphoinositides.


A lipid molecule that mediates a biological response. Lipid mediators form distinct classes of bioactive molecules rather than mere intermediates of lipid metabolism (for example, arachidonic acid metabolites (eicosanoids) or platelet-activating factor).


A chemical that transmits information from a neuron to a neighbouring cell.


Complex glycosphingolipids that carry three or more sugars on a ceramide backbone. Some of the sugars include sialic acid and N-acetylneuranimic acid.


Methods that include at least two stages of mass analysis, in conjunction with a dissociation process.


Commonly used chromatographic method. Analyte is separated by chromatographic material, which is immobilized as a thin layer on a solid support such a glass plate.


Small (nm–μm) spherical particles that are composed of lipid bilayers. Liposomes are used in biophysical and biochemical binding studies, as carriers in drug delivery and cosmetic formulations.


An endocannabinoid arachidonic acid metabolite (arachidonylethanolamine).


A discipline that aims at the quantitative and comprehensive analysis of all metabolites. Although the term 'metabolomic' is used here no side is taken with respect to the distinction between the two terms.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wenk, M. The emerging field of lipidomics. Nat Rev Drug Discov 4, 594–610 (2005).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing