Advertisement

Urinary Lipidomics

  • Phornpimon Tipthara
  • Visith Thongboonkerd
Chapter
Part of the Translational Bioinformatics book series (TRBIO, volume 14)

Abstract

Urinary lipidomics has become an attractive arena in current biomedical research and life science because the urine is an ideal source for discovery of non-invasive biomarkers for human diseases. However, urinary lipidome profiling is not too simple because lipid concentrations in the urine are relatively low and high levels of salts and other charged compounds can interfere with lipidome analysis. In this chapter, we provide a technical overview of mass spectrometry (MS)-based urinary lipidomics and its technical challenges, such as exosome isolation, lipid extraction, isomer/isobar identification and clinical applications, for the future success of this field.

Notes

Acknowledgements

This work was supported by Mahidol University research grant and the Thailand Research Fund (IRN60W0004 and IRG5980006).

References

  1. Alharbi FJ, Geberhiwot T, Hughes DA, Ward DG. A novel rapid MALDI-TOF-MS-based method for measuring urinary Globotriaosylceramide in Fabry patients. J Am Soc Mass Spectrom. 2016;27:719–25.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Barrios C, Spector TD, Menni C. Blood, urine and faecal metabolite profiles in the study of adult renal disease. Arch Biochem Biophys. 2016;589:81–92.CrossRefPubMedGoogle Scholar
  3. Becker GJ, Nicholls K. Lipiduria – with special relevance to Fabry disease. Clin Chem Lab Med. 2015;53(Suppl 2):s1465–70.PubMedGoogle Scholar
  4. Bielow C, Mastrobuoni G, Orioli M, Kempa S. On mass ambiguities in high-resolution shotgun lipidomics. Anal Chem. 2017;89:2986–94.CrossRefPubMedGoogle Scholar
  5. Boonla C, Youngjermchan P, Pumpaisanchai S, Tungsanga K, Tosukhowong P. Lithogenic activity and clinical relevance of lipids extracted from urines and stones of nephrolithiasis patients. Urol Res. 2011;39:9–19.CrossRefPubMedGoogle Scholar
  6. Bowman AP, Abzalimov RR, Shvartsburg AA. Broad separation of isomeric lipids by high-resolution differential ion mobility spectrometry with tandem mass spectrometry. J Am Soc Mass Spectrom. 2017;28:1552–61.CrossRefPubMedGoogle Scholar
  7. Byeon SK, Kim JY, Lee JS, Moon MH. Variations in plasma and urinary lipids in response to enzyme replacement therapy for Fabry disease patients by nanoflow UPLC-ESI-MS/MS. Anal Bioanal Chem. 2016;408:2265–74.CrossRefPubMedGoogle Scholar
  8. Cajka T, Fiehn O. Comprehensive analysis of lipids in biological systems by liquid chromatography-mass spectrometry. Trends Analyt Chem. 2014;61:192–206.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Cheruvanky A, Zhou H, Pisitkun T, Kopp JB, Knepper MA, Yuen PS, Star RA. Rapid isolation of urinary exosomal biomarkers using a nanomembrane ultrafiltration concentrator. Am J Physiol Renal Physiol. 2007;292:F1657–61.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Collins AJ, Foley RN, Chavers B, Gilbertson D, Herzog C, Johansen K, Kasiske B, Kutner N, Liu J, St Peter W, Guo H, Gustafson S, Heubner B, Lamb K, Li S, Li S, Peng Y, Qiu Y, Roberts T, Skeans M, Snyder J, Solid C, Thompson B, Wang C, Weinhandl E, Zaun D, Arko C, Chen SC, Daniels F, Ebben J, Frazier E, Hanzlik C, Johnson R, Sheets D, Wang X, Forrest B, Constantini E, Everson S, Eggers P, Agodoa L. United States renal data system 2011 annual data report: atlas of chronic kidney disease & end-stage renal disease in the United States. Am J Kidney Dis. 2012;59(A7):e1-A7,420.Google Scholar
  11. Damen CW, Isaac G, Langridge J, Hankemeier T, Vreeken RJ. Enhanced lipid isomer separation in human plasma using reversed-phase UPLC with ion-mobility/high-resolution MS detection. J Lipid Res. 2014;55:1772–83.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Del Boccio P, Raimondo F, Pieragostino D, Morosi L, Cozzi G, Sacchetta P, Magni F, Pitto M, Urbani A. A hyphenated microLC-Q-TOF-MS platform for exosomal lipidomics investigations: application to RCC urinary exosomes. Electrophoresis. 2012;33:689–96.CrossRefPubMedGoogle Scholar
  13. Dobrian AD, Lieb DC, Cole BK, Taylor-Fishwick DA, Chakrabarti SK, Nadler JL. Functional and pathological roles of the 12- and 15-lipoxygenases. Prog Lipid Res. 2011;50:115–31.CrossRefPubMedGoogle Scholar
  14. Erkan E, Zhao X, Setchell K, Devarajan P. Distinct urinary lipid profile in children with focal segmental glomerulosclerosis. Pediatr Nephrol. 2016;31:581–8.CrossRefPubMedGoogle Scholar
  15. Fahy E, Subramaniam S, Brown HA, Glass CK, Merrill AH Jr, Murphy RC, Raetz CR, Russell DW, Seyama Y, Shaw W, Shimizu T, Spener F, van Meer G, VanNieuwenhze MS, White SH, Witztum JL, Dennis EA. A comprehensive classification system for lipids. J Lipid Res. 2005;46:839–61.CrossRefPubMedGoogle Scholar
  16. Fahy E, Subramaniam S, Murphy RC, Nishijima M, Raetz CR, Shimizu T, Spener F, van Meer G, Wakelam MJ, Dennis EA. Update of the LIPID MAPS comprehensive classification system for lipids. J Lipid Res. 2009;50(Suppl):S9–14.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Ferris ME, Gipson DS, Kimmel PL, Eggers PW. Trends in treatment and outcomes of survival of adolescents initiating end-stage renal disease care in the United States of America. Pediatr Nephrol. 2006;21:1020–6.CrossRefPubMedGoogle Scholar
  18. Fuchs B. Analysis of phospolipids and glycolipids by thin-layer chromatography-matrix-assisted laser desorption and ionization mass spectrometry. J Chromatogr A. 2012;1259:62–73.CrossRefPubMedGoogle Scholar
  19. Fuchs B, Schiller J, Suss R, Schurenberg M, Suckau D. A direct and simple method of coupling matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) to thin-layer chromatography (TLC) for the analysis of phospholipids from egg yolk. Anal Bioanal Chem. 2007;389:827–34.CrossRefPubMedGoogle Scholar
  20. Fuchs B, Suss R, Schiller J. An update of MALDI-TOF mass spectrometry in lipid research. Prog Lipid Res. 2010;49:450–75.CrossRefPubMedGoogle Scholar
  21. Fuchs B, Suss R, Teuber K, Eibisch M, Schiller J. Lipid analysis by thin-layer chromatography – a review of the current state. J Chromatogr A. 2011;1218:2754–74.CrossRefPubMedGoogle Scholar
  22. Fuller M, Sharp PC, Rozaklis T, Whitfield PD, Blacklock D, Hopwood JJ, Meikle PJ. Urinary lipid profiling for the identification of fabry hemizygotes and heterozygotes. Clin Chem. 2005;51:688–94.CrossRefPubMedGoogle Scholar
  23. Gerl MJ, Sampaio JL, Urban S, Kalvodova L, Verbavatz JM, Binnington B, Lindemann D, Lingwood CA, Shevchenko A, Schroeder C, Simons K. Quantitative analysis of the lipidomes of the influenza virus envelope and MDCK cell apical membrane. J Cell Biol. 2012;196:213–21.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Graessler, J., Mehnert, C. S., Schulte, K. M., Bergmann, S., Strauss, S., Bornstein, T. D., Licinio, J., Wong, M. L., Birkenfeld, A. L., and Bornstein, S. R. (2017) Urinary Lipidomics: evidence for multiple sources and sexual dimorphism in healthy individuals. Pharmacogen J.18(2): 331-339Google Scholar
  25. Grove KJ, Voziyan PA, Spraggins JM, Wang S, Paueksakon P, Harris RC, Hudson BG, Caprioli RM. Diabetic nephropathy induces alterations in the glomerular and tubule lipid profiles. J Lipid Res. 2014;55:1375–85.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Guan XL, Wenk MR. Targeted and non-targeted analysis of membrane lipids using mass spectrometry. Methods Cell Biol. 2012;108:149–72.PubMedGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. Hines KM, Herron J, Xu L. Assessment of altered lipid homeostasis by HILIC-ion mobility-mass spectrometry-based lipidomics. J Lipid Res. 2017;58:809–19.CrossRefPubMedPubMedCentralGoogle Scholar
  29. Li M, Zhou Z, Nie H, Bai Y, Liu H. Recent advances of chromatography and mass spectrometry in lipidomics. Anal Bioanal Chem. 2011;399:243–9.CrossRefPubMedGoogle Scholar
  30. Massey KA, Nicolaou A. Lipidomics of oxidized polyunsaturated fatty acids. Free Radic Biol Med. 2013;59:45–55.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Matyash V, Liebisch G, Kurzchalia TV, Shevchenko A, Schwudke D. Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics. J Lipid Res. 2008;49:1137–46.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Merchant ML, Powell DW, Wilkey DW, Cummins TD, Deegens JK, Rood IM, McAfee KJ, Fleischer C, Klein E, Klein JB. Microfiltration isolation of human urinary exosomes for characterization by MS. Proteomics Clin Appl. 2010;4:84–96.CrossRefPubMedGoogle Scholar
  33. Min HK, Lim S, Chung BC, Moon MH. Shotgun lipidomics for candidate biomarkers of urinary phospholipids in prostate cancer. Anal Bioanal Chem. 2011;399:823–30.CrossRefPubMedGoogle Scholar
  34. Mirzoyan K, Baiotto A, Dupuy A, Marsal D, Denis C, Vinel C, Sicard P, Bertrand-Michel J, Bascands JL, Schanstra JP, Klein J, Saulnier-Blache JS. Increased urinary lysophosphatidic acid in mouse with subtotal nephrectomy: potential involvement in chronic kidney disease. J Physiol Biochem. 2016;72:803–12.CrossRefPubMedGoogle Scholar
  35. Mohr NM, Harland KK, Crabb V, Mutnick R, Baumgartner D, Spinosi S, Haarstad M, Ahmed A, Schweizer M, Faine B. Urinary squamous epithelial cells do not accurately predict urine culture contamination, but may predict urinalysis performance in predicting bacteriuria. Acad Emerg Med. 2016;23:323–30.CrossRefPubMedGoogle Scholar
  36. Monteiro M, Moreira N, Pinto J, Pires-Luis AS, Henrique R, Jeronimo C, Bastos ML, Gil AM, Carvalho M, Guedes d P. GC-MS metabolomics-based approach for the identification of a potential VOC-biomarker panel in the urine of renal cell carcinoma patients. J Cell Mol Med. 2017;21:2092–105.CrossRefPubMedPubMedCentralGoogle Scholar
  37. Nowling TK, Mather AR, Thiyagarajan T, Hernandez-Corbacho MJ, Powers TW, Jones EE, Snider AJ, Oates JC, Drake RR, Siskind LJ. Renal glycosphingolipid metabolism is dysfunctional in lupus nephritis. J Am Soc Nephrol. 2015;26:1402–13.CrossRefPubMedGoogle Scholar
  38. Okemoto K, Maekawa K, Tajima Y, Tohkin M, Saito Y. Cross-classification of human urinary Lipidome by sex, age, and body mass index. PLoS One. 2016;11:e0168188.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Paglia G, Astarita G. Metabolomics and lipidomics using traveling-wave ion mobility mass spectrometry. Nat Protoc. 2017;12:797–813.CrossRefPubMedGoogle Scholar
  40. Paglia G, Kliman M, Claude E, Geromanos S, Astarita G. Applications of ion-mobility mass spectrometry for lipid analysis. Anal Bioanal Chem. 2015;407:4995–5007.CrossRefPubMedGoogle Scholar
  41. Pradere JP, Klein J, Gres S, Guigne C, Neau E, Valet P, Calise D, Chun J, Bascands JL, Saulnier-Blache JS, Schanstra JP. LPA1 receptor activation promotes renal interstitial fibrosis. J Am Soc Nephrol. 2007;18:3110–8.CrossRefPubMedGoogle Scholar
  42. Pulfer M, Murphy RC. Electrospray mass spectrometry of phospholipids. Mass Spectrom Rev. 2003;22:332–64.CrossRefPubMedGoogle Scholar
  43. Raffield LM, Hsu FC, Cox AJ, Carr JJ, Freedman BI, Bowden DW. Predictors of all-cause and cardiovascular disease mortality in type 2 diabetes: diabetes heart study. Diabetol Metab Syndr. 2015;7:58.CrossRefPubMedPubMedCentralGoogle Scholar
  44. Rancoule C, Pradere JP, Gonzalez J, Klein J, Valet P, Bascands JL, Schanstra JP, Saulnier-Blache JS. Lysophosphatidic acid-1-receptor targeting agents for fibrosis. Expert Opin Investig Drugs. 2011;20:657–67.CrossRefPubMedGoogle Scholar
  45. Ren J, Mozurkewich EL, Sen A, Vahratian AM, Ferreri TG, Morse AN, Djuric Z. Total serum fatty acid analysis by GC-MS: assay validation and serum sample stability. Curr Pharm Anal. 2013;9:331–9.CrossRefPubMedPubMedCentralGoogle Scholar
  46. Rockwell HE, Gao F, Chen EY, McDaniel J, Sarangarajan R, Narain NR, Kiebish MA. Dynamic assessment of functional Lipidomic analysis in human urine. Lipids. 2016;51:875–86.CrossRefPubMedGoogle Scholar
  47. Rood IM, Deegens JK, Merchant ML, Tamboer WP, Wilkey DW, Wetzels JF, Klein JB. Comparison of three methods for isolation of urinary microvesicles to identify biomarkers of nephrotic syndrome. Kidney Int. 2010;78:810–6.CrossRefPubMedGoogle Scholar
  48. Saulnier-Blache JS, Feigerlova E, Halimi JM, Gourdy P, Roussel R, Guerci B, Dupuy A, Bertrand-Michel J, Bascands JL, Hadjadj S, Schanstra JP. Urinary lysophopholipids are increased in diabetic patients with nephropathy. J Diabetes Complicat. 2017;31:1103–8.CrossRefPubMedGoogle Scholar
  49. Schiller J, Suss R, Arnhold J, Fuchs B, Lessig J, Muller M, Petkovic M, Spalteholz H, Zschornig O, Arnold K. Matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) mass spectrometry in lipid and phospholipid research. Prog Lipid Res. 2004;43:449–88.CrossRefPubMedGoogle Scholar
  50. Schiller J, Suss R, Fuchs B, Muller M, Zschornig O, Arnold K. MALDI-TOF MS in lipidomics. Front Biosci. 2007;12:2568–79.CrossRefPubMedGoogle Scholar
  51. Skotland T, Ekroos K, Kauhanen D, Simolin H, Seierstad T, Berge V, Sandvig K, Llorente A. Molecular lipid species in urinary exosomes as potential prostate cancer biomarkers. Eur J Cancer. 2017;70:122–32.CrossRefPubMedGoogle Scholar
  52. Sud M, Fahy E, Cotter D, Brown A, Dennis EA, Glass CK, Merrill AH Jr, Murphy RC, Raetz CR, Russell DW, Subramaniam S. LMSD: LIPID MAPS structure database. Nucleic Acids Res. 2007;35:D527–32.CrossRefPubMedGoogle Scholar
  53. Svensson MK, Cederholm J, Eliasson B, Zethelius B, Gudbjornsdottir S. Albuminuria and renal function as predictors of cardiovascular events and mortality in a general population of patients with type 2 diabetes: a nationwide observational study from the Swedish National Diabetes Register. Diab Vasc Dis Res. 2013;10:520–9.CrossRefPubMedGoogle Scholar
  54. Taki T. TLC-blot (far-eastern blot) and its application to functional Lipidomics. Methods Mol Biol. 2015;1314:219–41.CrossRefPubMedGoogle Scholar
  55. Tam ZY, Ng SP, Tan LQ, Lin CH, Rothenbacher D, Klenk J, Boehm BO. Metabolite profiling in identifying metabolic biomarkers in older people with late-onset type 2 diabetes mellitus. Sci Rep. 2017;7:4392.CrossRefPubMedPubMedCentralGoogle Scholar
  56. Taylor DD, Zacharias W, Gercel-Taylor C. Exosome isolation for proteomic analyses and RNA profiling. Methods Mol Biol. 2011;728:235–46.CrossRefPubMedGoogle Scholar
  57. Thery C, Amigorena S, Raposo G, Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol. 2006;Chapter 3, Unit.Google Scholar
  58. Thomas MC, Mitchell TW, Harman DG, Deeley JM, Nealon JR, Blanksby SJ. Ozone-induced dissociation: elucidation of double bond position within mass-selected lipid ions. Anal Chem. 2008;80:303–11.CrossRefPubMedGoogle Scholar
  59. Thongboonkerd V. Current status of renal and urinary proteomics: ready for routine clinical application? Nephrol Dial Transplant. 2010;25:11–6.CrossRefPubMedGoogle Scholar
  60. Tipthara P, Thongboonkerd V. Differential human urinary lipid profiles using various lipid-extraction protocols: MALDI-TOF and LIFT-TOF/TOF analyses. Sci Rep. 2016;6:33756.CrossRefPubMedPubMedCentralGoogle Scholar
  61. Touboul D, Roy S, Germain DP, Baillet A, Brion F, Prognon P, Chaminade P, Laprevote O. Fast fingerprinting by MALDI-TOF mass spectrometry of urinary sediment glycosphingolipids in Fabry disease. Anal Bioanal Chem. 2005;382:1209–16.CrossRefPubMedGoogle Scholar
  62. Tran TH, Hughes J, Greenfeld C, Pham JT. Overview of current and alternative therapies for idiopathic membranous nephropathy. Pharmacotherapy. 2015;35:396–411.CrossRefPubMedGoogle Scholar
  63. Wenk MR. The emerging field of lipidomics. Nat Rev Drug Discov. 2005;4:594–610.CrossRefPubMedGoogle Scholar
  64. Wojcik R, Webb IK, Deng L, Garimella SV, Prost SA, Ibrahim YM, Baker ES, Smith RD. Lipid and glycolipid isomer analyses using ultra-high resolution ion mobility spectrometry separations. Int J Mol Sci. 2017;18:183.Google Scholar
  65. Yang JS, Lee JC, Byeon SK, Rha KH, Moon MH. Size dependent Lipidomic analysis of urinary exosomes from patients with prostate Cancer by flow field-flow fractionation and Nanoflow liquid chromatography-tandem mass spectrometry. Anal Chem. 2017;89:2488–96.CrossRefPubMedGoogle Scholar
  66. Zhao YY, Vaziri ND, Lin RC. Lipidomics: new insight into kidney disease. Adv Clin Chem. 2015;68:153–75.CrossRefPubMedGoogle Scholar
  67. Zhao M, Li M, Yang Y, Guo Z, Sun Y, Shao C, Li M, Sun W, Gao Y. A comprehensive analysis and annotation of human normal urinary proteome. Sci Rep. 2017;7:3024.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Phornpimon Tipthara
    • 1
  • Visith Thongboonkerd
    • 1
  1. 1.Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand

Personalised recommendations