Nutrition, Metabolism & Cardiovascular Diseases
Volume 19, Issue 11 , Pages 816-824 , December 2009

Metabolomics, a novel tool for studies of nutrition, metabolism and lipid dysfunction

  • M. Orešič

      Affiliations

    • Corresponding Author InformationTel.: +358 20 722 4491; fax: +358 20 722 7071.
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Received 8 April 2009 ,Revised 20 April 2009 ,Accepted 29 April 2009.

References 

  1. Tang J, Tan CY, Oresic M, Vidal-Puig A. Integrating post-genomic approaches as a strategy to advance our understanding of health and disease. Genome Med. 2009;1(3):e35
  2. Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science. 2005;307(5717):1915–1920
  3. Cascante M, Boros LG, Comin-Anduix B, de Atauri P, Centelles JJ, Lee PW-N. Metabolic control analysis in drug discovery and disease. Nat Biotechnol. 2002;20:243–249
  4. Oresic M, Vidal-Puig A, Hänninen V. Metabolomic approaches to phenotype characterization and applications to complex diseases. Expert Rev Mol Diagn. 2006;6(4):575–585
  5. van Ommen B. Nutrigenomics: exploiting systems biology in the nutrition and health arenas. Nutrition. 2004;20(1):4–8
  6. In:  Vance DE,  Vance JE editor. Biochemistry of lipids, lipoproteins and membranes. 5th ed. Amsterdam, The Netherlands: Elsevier B.V; 2008;
  7. Oresic M, Hänninen VA, Vidal-Puig A. Lipidomics: a new window to biomedical frontiers. Trends Biotechnol. 2008;26(12):647–652
  8. Jänis M, Laaksonen R, Oresic M. Metabolomic strategies to identify tissue specific effects of cardiovascular drugs. Exp Opin Drug Metab Toxicol. 2008;4(6):665–680
  9. Oresic M, Simell S, Sysi-Aho M, Näntö-Salonen K, Seppänen-Laakso T, Parikka V, et al. Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes. J Exp Med. 2008;205(13):2975–2984
  10. Unger R. Lipotoxic diseases. Annu Rev Med. 2002;53:319–336
  11. Medina-Gomez G, Gray S, Yetukuri L, Shimomura K, Campbell M, Curtis K, et al. PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet. 2007;3(4):e64
  12. Hartmann T, Kuchenbecker J, Grimm MOW. Alzheimer's disease: the lipid connection. J Neurochem. 2007;103(s1):159–170
  13. Han X, Holtzman DM, McKeel DW. Plasmalogen deficiency in early Alzheimer's disease subjects and in animal models: molecular characterization using electrospray ionization mass spectrometry. J Neurochem. 2001;77(4):1168–1180
  14. Kaddurah-Daouk R, McEvoy J, Baillie RA, Lee D, Yao JK, Doraiswamy PM, et al. Metabolomic mapping of atypical antipsychotic effects in schizophrenia. Mol Psychiatry. 2007;12(10):934–945
  15. Schwarz E, Prabakaran S, Whitfield P, Major H, Leweke FM, Koethe D, et al. High throughput lipidomic profiling of schizophrenia and bipolar disorder brain tissue reveals alterations of free fatty acids, phosphatidylcholines, and ceramides. J Proteome Res. 2008;7(10):4266–4277
  16. Menendez JA, Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer. 2007;7(10):763–777
  17. Kobayashi N, Barnard RJ, Henning SM, Elashoff D, Reddy ST, Cohen P, et al. Effect of altering dietary {omega}-6/{omega}-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E2. Clin Cancer Res. 2006;12(15):4662–4670
  18. Lusis AJ. Atherosclerosis. Nature. 2000;407(6801):233–241
  19. Haughey NJ, Steiner J, Nath A, McArthur JC, Sacktor N, Pardo C, et al. Converging roles for sphingolipids and cell stress in the progression of neuro-AIDS. Front Biosci. 2008;13:5120–5130
  20. Wikoff WR, Pendyala G, Siuzdak G, Fox HS. Metabolomic analysis of the cerebrospinal fluid reveals changes in phospholipase expression in the CNS of SIV-infected macaques. J Clin Invest. 2008;118(7):2661–2669
  21. Wenk MR. The emerging field of lipidomics. Nat Rev Drug Discov. 2005;4:594–610
  22. Pauling L, Robinson AB, Teranishi R, Cary P. Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography. Proc Nat Acad Sci U S A. 1971;68:2374–2376
  23. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al. The sequence of the human genome. Science. 2001;291(5507):1304–1351
  24. Collins F, Green E, Guttmacher A, Guyer M. A vision for the future of genomics research. Nature. 2003;422:835–847
  25. Fenn J, Mann M, Meng C, Wong S, Whitehouse C. Electrospray ionization for mass spectrometry of large biomolecules. Science. 1989;246(4926):64–71
  26. Goodacre R, Vaidyanathan S, Dunn WB, Harrigan GG, Kell DB. Metabolomics by numbers: acquiring and understanding global metabolite data. Trends Biotechnol. 2004;22(5):245–252
  27. van der Greef J, Stroobant P. Heijden Rvd. The role of analytical sciences in medical systems biology. Curr Opin Chem Biol. 2004;8(5):559–565
  28. Lindon JC, Holmes E, Nicholson JK. Metabonomics and its role in drug development and disease diagnosis. Expert Rev Mol Diag. 2004;4(2):189–199
  29. Ståhlman M, Ejsing CS, Tarasov K, Perman J, Borén J, Ekroos K. High-throughput shotgun lipidomics by quadrupole time-of-flight mass spectrometry. J Chromatogr B 2009:doi:10.1016/j.jchromb.2009.02.037.
  30. Han X, Gross RW. Shotgun lipidomics: electrospray ionization mass spectrometric analysis and quantitation of cellular lipidomes directly from crude extracts of biological samples. Mass Spectrom Rev. 2005;24:367–412
  31. Schwudke D, Liebisch G, Herzog R, Schmitz G, Shevchenko A. Shotgun lipidomics by tandem mass spectrometry under data-dependent acquisition control. Methods Enzymol. 2007;433:175–191
  32. Nordstrom A, O'Maille G, Qin C, Siuzdak G. Nonlinear data alignment for UPLC-MS and HPLC-MS based metabolomics: quantitative analysis of endogenous and exogenous metabolites in human serum. Anal Chem. 2006;78(10):3289–3295
  33. Murphy RC, Barkley RM, Zemski Berry K, Hankin J, Harrison K, Johnson C, et al. Electrospray ionization and tandem mass spectrometry of eicosanoids. Anal Biochem. 2005;346(1):1–42
  34. Hagio M, Matsumoto M, Fukushima M, Hara H, Ishizuka S. Improved analysis of bile acids in tissues and intestinal contents of rats using LC/ESI-MS. J Lipid Res. 2009;50(1):173–180
  35. Pilvi TK, Seppänen-Laakso T, Simolin H, Finckenberg P, Huotari A, Herzig K-H, et al. Metabolomic changes in fatty liver can be modified by dietary protein and calcium during energy restriction. World J Gastroenterol 2008;14(28):4462–72.
  36. Shaham O, Wei R, Wang TJ, Ricciardi C, Lewis GD, Vasan RS, et al. Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity. Mol Syst Biol. 2008;4:e214
  37. Sabatine MS, Liu E, Morrow DA, Heller E, McCarroll R, Wiegand R, et al. Metabolomic identification of novel biomarkers of myocardial ischemia. Circulation. 2005;112(25):3868–3875
  38. Broadhurst D, Kell D. Statistical strategies for avoiding false discoveries in metabolomics and related experiments. Metabolomics. 2006;2(4):171–196
  39. Thissen U, Wopereis S, van den Berg S, Bobeldijk I, Kleemann R, Kooistra T, et al. Improving the analysis of designed studies by combining statistical modelling with study design information. BMC Bioinformatics. 2009;10(1):e52
  40. Niemelä PS, Castillo S, Sysi-Aho M, Oresic M. Bioinformatics and computational methods for lipidomics. J Chromatogr B: doi: 10.1016/j.jchromb.2009.01.025.
  41. Katajamaa M, Oresic M. Data processing for mass spectrometry-based metabolomics. J Chromatogr A. 2007;1158(1-2):318–328
  42. Katajamaa M, Oresic M. Processing methods for differential analysis of LC/MS profile data. BMC Bioinformatics. 2005;6:179
  43. Katajamaa M, Miettinen J, Oresic M. MZmine: toolbox for processing and visualization of mass spectrometry based molecular profile data. Bioinformatics. 2006;22(5):634–636
  44. Kind T, Tolstikov V, Fiehn O, Weiss RH. A comprehensive urinary metabolomic approach for identifying kidney cancer. Anal Biochem. 2007;363(2):185–195
  45. Timischl B, Dettmer K, Kaspar H, Thieme M, Oefner PJ. Development of a quantitative, validated capillary electrophoresis-time of flight – mass spectrometry method with integrated high-confidence analyte identification for metabolomics. Electrophoresis. 2008;29(10):2203–2214
  46. Rogers S, Scheltema RA, Girolami M, Breitling R. Probabilistic assignment of formulas to mass peaks in metabolomics experiments. Bioinformatics. 2009;25(4):512–518
  47. Welthagen W, Shellie RA, Spranger J, Ristow M, Zimmermann R, Fiehn O. Comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC—GC-TOF) for high resolution metabolomics: biomarker discovery on spleen tissue extracts of obese NZO compared to lean C57BL/6 mice. Metabolomics. 2005;1(1):65–73
  48. Koek MM, Muilwijk B, van Stee LLP, Hankemeier T. Higher mass loadability in comprehensive two-dimensional gas chromatography-mass spectrometry for improved analytical performance in metabolomics analysis. J Chromatogr A. 2008;1186(1-2):420–429
  49. Bobeldijk I, Hekman M, de Vries-van der Weij J, Coulier L, Ramaker R, Kleemann R, et al. Quantitative profiling of bile acids in biofluids and tissues based on accurate mass high resolution LC-FT-MS: compound class targeting in a metabolomics workflow. J Chromatogr B. 2008;871(2):306–313
  50. Sysi-Aho M, Katajamaa M, Yetukuri L, Oresic M. Normalization method for metabolomics data using optimal selection of multiple internal standards. BMC Bioinformatics. 2007;8:e93
  51. Bijlsma S, Bobeldijk I, Verheij ER, Ramaker R, Kochhar S, Macdonald IA, et al. Large-scale human metabolomics studies: a strategy for data (pre-) processing and validation. Anal Chem. 2006;78(2):567–574
  52. Kanehisa M, Araki M, Goto S, Hattori M, Hirakawa M, Itoh M, et al. KEGG for linking genomes to life and the environment. Nucl Acids Res. 2008;36:D480–D484
  53. Wishart DS, Knox C, Guo AC, Eisner R, Young N, Gautam B, et al. HMDB: a knowledgebase for the human metabolome. Nucl Acids Res. 2009;37:D603–D610
  54. Aura AM, Mattila I, Seppänen-Laakso T, Miettinen J, Oksman-Caldentey KM, Oresic M. Microbial metabolism of catechin stereoisomers by human faecal microbiota: comparison of targeted analysis and a non-targeted metabolomics method. Phytochem Lett. 2008;1:18–22
  55. Nikkilä J, Sysi-Aho M, Ermolov A, Seppänen-Laakso T, Simell O, Kaski S, et al. Gender dependent progression of systemic metabolic states in early childhood. Mol Syst Biol. 2008;4:e197
  56. Lenz EM, Bright J, Wilson ID, Hughes A, Morrisson J, Lindberg H, et al. Metabonomics, dietary influences and cultural differences: a 1H NMR-based study of urine samples obtained from healthy British and Swedish subjects. J Pharm Biomed Anal. 2004;36(4):841–849
  57. Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA. 2004;101(44):15718–15723
  58. Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA. 2005;102(31):11070–11075
  59. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444(7122):1022–1023
  60. Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, et al. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci USA. 2009;106(10):3698–3703
  61. Pietiläinen KH, Sysi-Aho M, Rissanen A, Seppänen-Laakso T, Yki-Järvinen H, Kaprio J, 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(2):e218
  62. Pietiläinen KH, Naukkarinen J, Rissanen A, Saharinen J, Ellonen P, Keränen H, et al. Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity. PLoS Med. 2008;5(3):e51
  63. Kolak M, Westerbacka J, Velagapudi VR, Wagsater D, Yetukuri L, Makkonen J, et al. Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity. Diabetes. 2007;56(8):1960–1968
  64. Virtue S, Vidal-Puig A. It's not how fat you are, it's what you do with it that counts. PLoS Biol. 2008;6(9):e237
  65. Grundy S, Denke M. Dietary influences on serum lipids and lipoproteins. J Lipid Res. 1990;31(7):1149–1172
  66. Kotronen A, Velagapudi VR, Yetukuri L, Westerbacka J, Bergholm R, Ekroos K, et al. Saturated fatty acids containing triacylglycerols are better markers of insulin resistance than total serum triacylglycerol concentrations. Diabetologia. 2009;52(4):684–690
  67. Maeba R, Maeda T, Kinoshita M, Takao K, Takenaka H, Kusano J, et al. Plasmalogens in human serum positively correlate with high-density lipoprotein and decrease with aging. J Atheroscler Thromb. 2007;14(1):12–18
  68. Wopereis S, Rubingh CM, van Erk MJ, Verheij ER, van Vliet T, Cnubben NHP, et al. Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes. PLoS ONE. 2009;4(2):e4525
  69. Zhao X, Peter A, Fritsche J, Elcnerova M, Fritsche A, Haring H-U, et al. Changes of the plasma metabolome during an oral glucose tolerance test: is there more than glucose to look at?. Am J Physiol Endocrinol Metab. 2009;296(2):E384–E393
  70. Walsh MC, Brennan L, Malthouse JPG, Roche HM, Gibney MJ. Effect of acute dietary standardization on the urinary, plasma, and salivary metabolomic profiles of healthy humans. Am J Clin Nutr. 2006;84(3):531–539
  71. Fardet A, Llorach R, Orsoni A, Martin J-F, Pujos-Guillot E, Lapierre C, et al. Metabolomics provide new insight on the metabolism of dietary phytochemicals in rats. J Nutr. 2008;138(7):1282–1287
  72. Aura A-M, Oikarinen S, Mutanen M, Heinonen S-M, Adlercreutz H, Virtanen H, et al. Suitability of a batch in vitro fermentation model using human faecal microbiota for prediction of conversion of flaxseed lignans to enterolactone with reference to an in vivo rat model. Eur J Nutr. 2006;45(1):45–51
  73. Aura A-M, Martin-Lopez P, O'Leary KA, Williamson G, Oksman-Caldentey K-M, Poutanen K, et al. In vitro metabolism of anthocyanins by human gut microflora. Eur J Nutr. 2005;44(3):133–142
  74. Heinonen S-M, Wahala K, Liukkonen K-H, Aura A-M, Poutanen K, Adlercreutz H. Studies of the in vitro intestinal metabolism of isoflavones aid in the identification of their urinary metabolites. J Agric Food Chem. 2004;52(9):2640–2646
  75. Kong H, Wang M, Venema K, Maathuis A, van der Heijden R, van der Greef J, et al. Bioconversion of red ginseng saponins in the gastro-intestinal tract in vitro model studied by high-performance liquid chromatography-high resolution Fourier transform ion cyclotron resonance mass spectrometry. J Chromatogr A. 2009;1216(11):2195–2203
  76. Lankinen M, Schwab U, Gopalacharyulu PV, Seppänen-Laakso T, Yetukuri L, Sysi-Aho M, et al. Dietary carbohydrate modification alters serum metabolic profiles in individuals with the metabolic syndrome. Nutr Metab Cardiovasc Dis 2009:In press, doi:10.1016/j.numecd.2009.04.009.
  77. Lankinen M, Schwab U, Erkkilä A, Seppänen-Laakso T, Hannila M-L, Mussalo H, et al. Fatty fish intake decreases lipids related to inflammation and insulin signaling – a lipidomics approach. PLoS ONE. 2009;4(4):e5258
  78. Schwab U, Seppänen-Laakso T, Yetukuri L, Ågren J, Kolehmainen M, Laaksonen DE, et al. Triacylglycerol fatty acid composition in diet-induced weight loss in subjects with abnormal glucose metabolism – the GENOBIN Study. PLoS ONE. 2008;3(7):e2630
  79. Smilowitz JT, Wiest MM, Watkins SM, Teegarden D, Zemel MB, German JB, et al. Lipid metabolism predicts changes in body composition during energy restriction in overweight humans. J Nutr. 2009;139(2):222–229
  80. Chorell E, Moritz T, Branth S, Antti H, Svensson M. A predictive metabolomics evaluation of nutrition-modulated metabolic stress responses in human blood serum during the early recovery phase of strenuous physical exercise. J Proteome Res 2009:doi:10.1021/pr900081q.

PII: S0939-4753(09)00120-3

doi: 10.1016/j.numecd.2009.04.018

Nutrition, Metabolism & Cardiovascular Diseases
Volume 19, Issue 11 , Pages 816-824 , December 2009