Current Atherosclerosis Reports

, Volume 12, Issue 3, pp 194–201 | Cite as

Lipidomics as a Tool for the Study of Lipoprotein Metabolism



Although technologies for lipidomic and proteomic investigations have developed very recently, lipidomic and proteomic studies of plasma lipoproteins have already provided several impressive examples of detailed characterization of distinct metabolic pathways potentially involved in lipoprotein metabolism in both health and disease states (obesity, insulin resistance, fatty liver disease) as well as under lifestyle and dietary modification (fish consumption, carbohydrates, probiotics) and lipid-modifying treatments (statins, low-density lipoprotein apheresis). Available lipidomic methodologies have facilitated detailed characterization of lipid classes and molecular species present in plasma as well as in lipoprotein fractions. Together with emerging proteomic techniques, lipidomics of plasma lipoproteins will soon provide molecular details of lipoprotein composition, which will ultimately be translated into integrated knowledge of the structure, metabolism, and function of lipoproteins in health and disease.


Lipidome Plasma Lipoproteins Lipids VLDL LDL HDL 


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Vaisar T: Thematic Review Series: Proteomics. Proteomic analysis of lipid-protein complexes. J Lipid Res 2009, 50:781–786.CrossRefPubMedGoogle Scholar
  2. 2.
    Hoofnagle AN, Heinecke JW: Lipoproteomics: using mass spectrometry-based proteomics to explore the assembly, structure, and function of lipoproteins. J Lipid Res 2009, 50:1967–1975.CrossRefPubMedGoogle Scholar
  3. 3.
    Davidsson P, Hulthe J, Fagerberg B, Camejo G: Proteomics of apolipoproteins and associated proteins from plasma high-density lipoproteins. Arterioscler Thromb Vasc Biol 2010, 30:156–163.CrossRefPubMedGoogle Scholar
  4. 4.
    Oresic M, Hanninen VA, Vidal-Puig A: Lipidomics: a new window to biomedical frontiers. Trends Biotechnol 2008, 26:647–652.CrossRefPubMedGoogle Scholar
  5. 5.
    Seppanen-Laakso T, Oresic M: How to study lipidomes. J Mol Endocrinol 2009, 42:185–190.CrossRefPubMedGoogle Scholar
  6. 6.
    • Wiesner P, Leidl K, Boettcher A, et al.: Lipid profiling of FPLC-separated lipoprotein fractions by electrospray ionization tandem mass spectrometry. J Lipid Res 2009, 50:574–585. This is a pioneering study of the lipidomics of isolated plasma lipoproteins (VLDL, LDL, HDL).CrossRefPubMedGoogle Scholar
  7. 7.
    Sysi-Aho M, Vehtari A, Velagapudi VR, et al.: Exploring the lipoprotein composition using Bayesian regression on serum lipidomic profiles. Bioinformatics 2007, 23:i519–528.CrossRefPubMedGoogle Scholar
  8. 8.
    • Kontush A, Therond P, Zerrad A, et al.: Preferential sphingosine-1-phosphate enrichment and sphingomyelin depletion are key features of small dense HDL3 particles: relevance to antiapoptotic and antioxidative activities. Arterioscler Thromb Vasc Biol 2007, 27:1843–1849. This is a pioneering study of the lipidome of isolated lipoprotein subclasses (HDL2b, 2a, 3a, 3b, 3c).CrossRefPubMedGoogle Scholar
  9. 9.
    Hansel B, Giral P, Nobecourt E, et al.: Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense high-density lipoprotein particles displaying impaired antioxidative activity. J Clin Endocrinol Metab 2004, 89:4963–4971.CrossRefPubMedGoogle Scholar
  10. 10.
    Kontush A, Chantepie S, Chapman MJ: Small, dense HDL particles exert potent protection of atherogenic LDL against oxidative stress. Arterioscler Thromb Vasc Biol 2003, 23:1881–1888.CrossRefPubMedGoogle Scholar
  11. 11.
    Nilsson A, Duan RD: Absorption and lipoprotein transport of sphingomyelin. J Lipid Res 2006, 47:154–171.CrossRefPubMedGoogle Scholar
  12. 12.
    Duong PT, Collins HL, Nickel M, et al.: Characterization of nascent HDL particles and microparticles formed by ABCA1-mediated efflux of cellular lipids to apoA-I. J Lipid Res 2006, 47:832–843.CrossRefPubMedGoogle Scholar
  13. 13.
    Nakamura Y, Kotite L, Gan Y, et al.: Molecular mechanism of reverse cholesterol transport: reaction of pre-beta-migrating high-density lipoprotein with plasma lecithin/cholesterol acyltransferase. Biochemistry 2004, 43:14811–14820.CrossRefPubMedGoogle Scholar
  14. 14.
    Subbaiah PV, Liu M: Role of sphingomyelin in the regulation of cholesterol esterification in the plasma lipoproteins. Inhibition of lecithin-cholesterol acyltransferase reaction. J Biol Chem 1993, 268:20156–20163.PubMedGoogle Scholar
  15. 15.
    Asztalos B, Zhang W, Roheim PS, Wong L: Role of free apolipoprotein A-I in cholesterol efflux. Formation of pre-alpha-migrating high-density lipoprotein particles. Arterioscler Thromb Vasc Biol 1997, 17:1630–1636.PubMedGoogle Scholar
  16. 16.
    de Souza JA, Vindis C, Negre-Salvayre A, et al.: Small, dense HDL3 particles attenuates apoptosis in endothelial cells: pivotal role of apolipoprotein A-I. J Cell Mol Med 2009 (in press).Google Scholar
  17. 17.
    Catalano G, Julia Z, Frisdal E, et al.: Torcetrapib differentially modulates the biological activities of hdl2 and hdl3 particles in the reverse cholesterol transport pathway. Arterioscler Thromb Vasc Biol 2009, 29:268–275.CrossRefPubMedGoogle Scholar
  18. 18.
    Zerrad-Saadi A, Therond P, Chantepie S, et al.: HDL3-mediated inactivation of LDL-associated phospholipid hydroperoxides is determined by the redox status of Apolipoprotein A-I and HDL particle surface lipid rigidity: relevance to inflammation and atherogenesis. Arterioscler Thromb Vasc Biol 2009, 29:2169–2175.CrossRefPubMedGoogle Scholar
  19. 19.
    Taylor AJ, Villines TC, Stanek EJ, et al.: Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med 2009, 361:2113–2122.CrossRefPubMedGoogle Scholar
  20. 20.
    Kontush A, Guerin M, Chapman MJ: Spotlight on HDL-raising therapies: insights from the torcetrapib trials. Nat Clin Pract Cardiovasc Med 2008, 5:329–336.CrossRefPubMedGoogle Scholar
  21. 21.
    • Pietilainen KH, Sysi-Aho M, Rissanen A, et al.: Acquired obesity is associated with changes in the serum lipidomic profile independent of genetic effects—a monozygotic twin study. PLoS One 2007, 2:e218. This is an elegant demonstration of specific alterations in the serum lipidome in acquired obesity.CrossRefPubMedGoogle Scholar
  22. 22.
    de Mello VD, Lankinen M, Schwab U, et al.: Link between plasma ceramides, inflammation and insulin resistance: association with serum IL-6 concentration in patients with coronary heart disease. Diabetologia 2009, 52:2612–2615.CrossRefPubMedGoogle Scholar
  23. 23.
    Kotronen A, Seppanen-Laakso T, Westerbacka J, et al.: Comparison of lipid and fatty acid composition of the liver, subcutaneous and intra-abdominal adipose tissue, and serum. Obesity (Silver Spring) 2009 (in press).Google Scholar
  24. 24.
    • Kotronen A, Velagapudi VR, Yetukuri L, et al.: Serum saturated fatty acids containing triacylglycerols are better markers of insulin resistance than total serum triacylglycerol concentrations. Diabetologia 2009, 52:684–690. This is an excellent lipidomics-based detailing of the relationship between insulin resistance and circulating TG levels.CrossRefPubMedGoogle Scholar
  25. 25.
    Puri P, Wiest MM, Cheung O, et al.: The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology 2009, 50:1827–1838.CrossRefPubMedGoogle Scholar
  26. 26.
    Kotronen A, Seppanen-Laakso T, Westerbacka J, et al.: Hepatic stearoyl-CoA desaturase (SCD)-1 activity and diacylglycerol but not ceramide concentrations are increased in the nonalcoholic human fatty liver. Diabetes 2009, 58:203–208.CrossRefPubMedGoogle Scholar
  27. 27.
    Kolak M, Westerbacka J, Velagapudi VR, et al.: Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity. Diabetes 2007, 56:1960–1968.CrossRefPubMedGoogle Scholar
  28. 28.
    Yetukuri L, Katajamaa M, Medina-Gomez G, et al.: Bioinformatics strategies for lipidomics analysis: characterization of obesity related hepatic steatosis. BMC Syst Biol 2007, 1:12.CrossRefPubMedGoogle Scholar
  29. 29.
    • Graessler J, Schwudke D, Schwarz PE, Top-down lipidomics reveals ether lipid deficiency in blood plasma of hypertensive patients. PLoS One 2009, 4:e6261. This is the first demonstration of abnormalities in the plasma lipidome in hypertension.CrossRefPubMedGoogle Scholar
  30. 30.
    • Guerrera IC, Astarita G, Jais JP, et al.: A novel lipidomic strategy reveals plasma phospholipid signatures associated with respiratory disease severity in cystic fibrosis patients. PLoS One 2009, 4:e7735. This is the first demonstration of abnormalities in the plasma lipidome in cystic fibrosis.CrossRefPubMedGoogle Scholar
  31. 31.
    Schwab U, Seppanen-Laakso T, Yetukuri L, et al.: Triacylglycerol fatty acid composition in diet-induced weight loss in subjects with abnormal glucose metabolism—the GENOBIN study. PLoS One 2008, 3:e2630.CrossRefPubMedGoogle Scholar
  32. 32.
    Lankinen M, Schwab U, Erkkila A, et al.: Fatty fish intake decreases lipids related to inflammation and insulin signaling—a lipidomics approach. PLoS One 2009, 4:e5258.CrossRefPubMedGoogle Scholar
  33. 33.
    Lankinen M, Schwab U, Gopalacharyulu PV, et al.: Dietary carbohydrate modification alters serum metabolic profiles in individuals with the metabolic syndrome. Nutr Metab Cardiovasc Dis 2009 (in press).Google Scholar
  34. 34.
    Kekkonen RA, Sysi-Aho M, Seppanen-Laakso T, et al.: Effect of probiotic Lactobacillus rhamnosus GG intervention on global serum lipidomic profiles in healthy adults. World J Gastroenterol 2008, 14:3188–3194.CrossRefPubMedGoogle Scholar
  35. 35.
    Altmaier E, Kastenmuller G, Romisch-Margl W, et al.: Variation in the human lipidome associated with coffee consumption as revealed by quantitative targeted metabolomics. Mol Nutr Food Res 2009, 53:1357–1365.CrossRefPubMedGoogle Scholar
  36. 36.
    • Bergheanu SC, Reijmers T, Zwinderman AH, et al.: Lipidomic approach to evaluate rosuvastatin and atorvastatin at various dosages: investigating differential effects among statins. Curr Med Res Opin 2008, 24:2477–2487. This is a pioneering study of the differential effects of rosuvastatin and atorvastatin on the plasma lipidome, notably on the SM/(SM+PC) ratio.CrossRefPubMedGoogle Scholar
  37. 37.
    Jiang XC, Paultre F, Pearson TA, et al.: Plasma sphingomyelin level as a risk factor for coronary artery disease. Arterioscler Thromb Vasc Biol 2000, 20:2614–2618.PubMedGoogle Scholar
  38. 38.
    Laaksonen R, Katajamaa M, Paiva H, et al.: A systems biology strategy reveals biological pathways and plasma biomarker candidates for potentially toxic statin-induced changes in muscle. PLoS One 2006, 1:e97.CrossRefPubMedGoogle Scholar
  39. 39.
    Laaksonen R, Janis MT, Oresic M: Lipidomics-based safety biomarkers for lipid-lowering treatments. Angiology 2008, 59(2 Suppl):65S–68S.CrossRefPubMedGoogle Scholar
  40. 40.
    Tselmin S, Schmitz G, Julius U, et al.: Acute effects of lipid apheresis on human serum lipidome. Atheroscler Suppl 2009, 10:27.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Université Pierre et Marie Curie-Paris 6ParisFrance
  2. 2.AP-HPGroupe hospitalier Pitié-SalpétrièreParisFrance
  3. 3.Dyslipidemia, Inflammation and Atherosclerosis Research Unit (UMR 939)National Institute for Health and Medical Research (INSERM)ParisFrance
  4. 4.INSERM Unit 939, Pavillon Benjamin DelessertHôpital de la PitiéParisFrance

Personalised recommendations