Skip to main content
SpringerLink
Log in

Mass Spectrometry-Based Lipidomics for Biomarker Research

  • Living reference work entry
  • First Online:
General Methods in Biomarker Research and their Applications

  • 204 Accesses

Abstract

As fundamental components of cellular membrane, metabolic and energy storage units, and signaling molecules, lipids play key roles in many pathophysiological processes. The systematic study of lipid molecular species and their interactions in biological samples, or the so-called lipidomics study, can assist with the understanding of the general condition of the whole biological system. Qualitative and quantitative determination of the subtle alterations of lipids in biological systems caused by genetics, diet, environment, and therapeutic interventions will not only facilitate in uncovering the pathophysiological role of lipids in disease onset and development but will also help to identify novel biomarkers for early detection, diagnosis, and prognosis of disease. Currently, the tremendous innovations in mass spectrometry and chromatographic techniques have largely driven the development of lipidomics. It has become an emerging approach extensively applied in biomarker research.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Abbreviations

AD:

Alzheimer’s Disease

APCI:

Atmospheric Pressure Chemical Ionization

CE:

Cholesteryl Ester

Cer:

Ceramide

CL:

Cardiolipin

DAG:

Diacylglycerol

DESI:

Desorption Electrospray Ionization

DHA:

Docosahexaenoic Acid

EIC:

Extracted Ion Chromatography

ESI:

Electrospray Ionization

FFA:

Free Fatty Acid

FT-ICR:

Fourier Transform Ion Cyclotron Resonance

FWHM:

Full Width at Half Maximum

GC:

Gas Chromatography

GL:

Glycerolipid

GSL:

Glycosphingolipid

HCD:

High Collision Dissociation

HILIC:

Hydrophilic Interaction Liquid Chromatography

HPLC:

High-Performance Liquid Chromatography

IMS:

Imaging Mass Spectrometry

IS:

Internal Standard

IT:

Ion Trap

LAESI:

Laser Ablation Electrospray Ionization

LC:

Liquid Chromatography

LDI:

Matrix-Free Laser Desorption Ionization

LPC:

Lyso-PC

LTQ-Orbitrap:

Hybrid Linear Ion Trap-Orbitrap Tandem Mass Spectrometer

MALDI:

Matrix-Assisted Laser Desorption/Ionization

MCI:

Mild Cognitive Impairment

MDMS:

Multidimensional MS

MLCL:

Monolysocardiolipin

MRM:

Multiple reaction monitoring

MS:

Mass Spectrometry

MSn :

Tandem Mass Spectrometry

MTBE:

Methyl Tert-Butyl Ether

NPLC:

Normal Phase Liquid Chromatography

PA:

Phosphatidic Acid

PC:

Phosphatidylcholine

PE:

Phosphatidylethanolamine

PI:

Phosphatidylinositol

PL:

Phospholipid

PS:

Phosphatidylserine

Q:

Quadrupole

QC:

Quality Control

QqQ:

Triple Quadrupole

RPLC:

Reversed-Phase Liquid Chromatography

SIMS:

Second Ion Ms

SL:

Sphingolipid

SM:

Sphingomyelin

SPE:

Solid-Phase Extraction

TAG:

Triacylglycerol

TLC:

Thin-Layer Chromatography

TOF:

Time-of-Flight

TR:

Retention Time

UHPLC:

Ultrahigh-Performance Liquid Chromatography

References

  • Bird SS, Marur VR, Sniatynski MJ, Greenberg HK, Kristal BS. Lipidomics profiling by high-resolution LC-MS and high-energy collisional dissociation fragmentation: focus on characterization of mitochondrial cardiolipins and monolysocardiolipins. Anal Chem. 2011;83(3):940–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959;37(8):911–7.

    Article  CAS  PubMed  Google Scholar 

  • Bou Khalil M, Hou W, Zhou H, et al. Lipidomics era: accomplishments and challenges. Mass Spectrom Rev. 2010;29(6):877–929.

    Article  PubMed  Google Scholar 

  • Brown HA, Murphy RC. Working towards an exegesis for lipids in biology. Nat Chem Biol. 2009;5(9):602–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Brugger B, Glass B, Haberkant P, Leibrecht I, Wieland FT, Krausslich HG. The HIV lipidome: a raft with an unusual composition. Proc Natl Acad Sci U S A. 2006;103(8):2641–6.

    Article  PubMed Central  PubMed  Google Scholar 

  • Clayton EH, Hanstock TL, Hirneth SJ, Kable CJ, Garg ML, Hazell PL. Long-chain omega-3 polyunsaturated fatty acids in the blood of children and adolescents with juvenile bipolar disorder. Lipids. 2008;43(11):1031–8.

    Article  CAS  PubMed  Google Scholar 

  • Cunnane SC, Schneider JA, Tangney C, et al. Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis. 2012;29(3):691–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cvetkovic B, Vucic V, Cvetkovic Z, Popovic T, Glibetic M. Systemic alterations in concentrations and distribution of plasma phospholipids in prostate cancer patients. Med Oncol. 2012;29(2):809–14.

    Article  CAS  PubMed  Google Scholar 

  • de Grauw JC, van de Lest CH, van Weeren PR. A targeted lipidomics approach to the study of eicosanoid release in synovial joints. Arthritis Res Ther. 2011;13(4):R123.

    Article  PubMed Central  PubMed  Google Scholar 

  • Dennis EA, Deems RA, Harkewicz R, et al. A mouse macrophage lipidome. J Biol Chem. 2010;285(51):39976–85.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ejsing CS, Sampaio JL, Surendranath V, et al. Global analysis of the yeast lipidome by quantitative shotgun mass spectrometry. Proc Natl Acad Sci U S A. 2009;106(7):2136–41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fahy E, Subramaniam S, Brown HA, et al. A comprehensive classification system for lipids. J Lipid Res. 2005;46(5):839–61.

    Article  CAS  PubMed  Google Scholar 

  • Folch J, Lees M, Stanley GHS. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem. 1957;226(1):497–509.

    CAS  PubMed  Google Scholar 

  • Fonteh AN, Chiang J, Cipolla M, et al. Alterations in cerebrospinal fluid glycerophospholipids and phospholipase A2 activity in Alzheimer’s disease. J Lipid Res. 2013;54(10):2884–97.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gonzalez-Covarrubias V. Lipidomics in longevity and healthy aging. Biogerontology. 2013;14:663–72.

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez-Covarrubias V, Beekman M, Uh H-W, et al. Lipidomics of familial longevity. Aging Cell. 2013;12(3):426–34.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Goto-Inoue N, Hayasaka T, Zaima N, Setou M. Imaging mass spectrometry for lipidomics. Biochim Biophys Acta. 2011;1811(11):961–9.

    Article  CAS  PubMed  Google Scholar 

  • Gregory KE, Bird SS, Gross VS, et al. Method development for fecal lipidomics profiling. Anal Chem. 2013;85(2):1114–23.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Guo Y, Wang X, Qiu L, et al. Probing gender-specific lipid metabolites and diagnostic biomarkers for lung cancer using Fourier transform ion cyclotron resonance mass spectrometry. Clin Chim Acta. 2012;414:135–41.

    Article  CAS  PubMed  Google Scholar 

  • Han XL, Gross RW. Global analyses of cellular lipidomes directly from crude extracts of biological samples by ESI mass spectrometry: a bridge to lipidomics. J Lipid Res. 2003;44(6):1071–9.

    Article  CAS  PubMed  Google Scholar 

  • 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. 2005a;24(3):367–412.

    Article  CAS  PubMed  Google Scholar 

  • Han X, Gross RW. Shotgun lipidomics: multidimensional MS analysis of cellular lipidomes. Expert Rev Proteomics. 2005b;2(2):253–64.

    Article  CAS  PubMed  Google Scholar 

  • Han X, Yang K, Gross RW. Microfluidics-based electrospray ionization enhances the intrasource separation of lipid classes and extends identification of individual molecular species through multi-dimensional mass spectrometry: development of an automated high-throughput platform for shotgun lipidomics. Rapid Commun Mass Spectrom. 2008;22(13):2115–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Han X, Rozen S, Boyle SH, et al. Metabolomics in early Alzheimer’s disease: identification of altered plasma sphingolipidome using shotgun lipidomics. PLoS One. 2011;6(7):e21643.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Han X, Yang K, Gross RW. Multi-dimensional mass spectrometry-based shotgun lipidomics and novel strategies for lipidomic analyses. Mass Spectrom Rev. 2012;31(1):134–78.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Haynes CA, Allegood JC, Wang EW, Kelly SL, Sullards MC, Merrill Jr AH. Factors to consider in using [U-C]palmitate for analysis of sphingolipid biosynthesis by tandem mass spectrometry. J Lipid Res. 2011;52(8):1583–94.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hilvo M, Gade S, Hyotylainen T, et al. Monounsaturated fatty acids in serum triacylglycerols are associated with response to neoadjuvant chemotherapy in breast cancer patients. Int J Cancer. 2013;134:1725–33.

    Article  PubMed  Google Scholar 

  • Hou W, Zhou H, Elisma F, Bennett SA, Figeys D. Technological developments in lipidomics. Brief Funct Genomic Proteomic. 2008;7(5):395–409.

    Article  CAS  PubMed  Google Scholar 

  • Hu C. Systems biology for evaluating system-based medicine. Thesis, Leiden University. ISBN: 978-90-74538-77-0. Printed by Wöhrmann Print Service, Zutphen, The Netherlands; 2012, p. 6–12.

    Google Scholar 

  • Hu C, Hoene M, Zhao X, et al. Lipidomics analysis reveals efficient storage of hepatic triacylglycerides enriched in unsaturated fatty acids after one bout of exercise in mice. PLoS One. 2010;5(10):e13318.

    Article  PubMed Central  PubMed  Google Scholar 

  • Hutchins PM, Barkley RM, Murphy RC. Separation of cellular nonpolar neutral lipids by normal-phase chromatography and analysis by electrospray ionization mass spectrometry. J Lipid Res. 2008;49(4):804–13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Iuliano L, Pacelli A, Ciacciarelli M, et al. Plasma fatty acid lipidomics in amnestic mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis. 2013;36(3):545–53.

    CAS  PubMed  Google Scholar 

  • Jelonek K, Ros M, Pietrowska M, Widlak P. Cancer biomarkers and mass spectrometry-based analyses of phospholipids in body fluids. Clin Lipidol. 2013;8(1):137–50.

    Article  CAS  Google Scholar 

  • Ji J, Kline AE, Amoscato A, et al. Lipidomics identifies cardiolipin oxidation as a mitochondrial target for redox therapy of brain injury. Nat Neurosci. 2012;15(10):1407–13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jove M, Ayala V, Ramirez-Nunez O, et al. Lipidomic and metabolomic analyses reveal potential plasma biomarkers of early atheromatous plaque formation in hamsters. Cardiovasc Res. 2013;97(4):642–52.

    Article  CAS  PubMed  Google Scholar 

  • Kim H, Min HK, Kong G, Moon MH. Quantitative analysis of phosphatidylcholines and phosphatidylethanolamines in urine of patients with breast cancer by nanoflow liquid chromatography/tandem mass spectrometry. Anal Bioanal Chem. 2009;393(6–7):1649–56.

    Article  CAS  PubMed  Google Scholar 

  • Laaksonen R, Janis MT, Oresic M. Lipidomics-based safety biomarkers for lipid-lowering treatments. Angiology. 2008;59(2 Suppl):65S–8.

    Article  PubMed  Google Scholar 

  • Lagarde M, Bernoud-Hubac N, Calzada C, Vericel E, Guichardant M. Lipidomics of essential fatty acids and oxygenated metabolites. Mol Nutr Food Res. 2013;57(8):1347–58.

    Article  CAS  PubMed  Google Scholar 

  • Li F, Qin X, Chen H, et al. Lipid profiling for early diagnosis and progression of colorectal cancer using direct-infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. Rapid Commun Mass Spectrom. 2013a;27(1):24–34.

    Article  PubMed  Google Scholar 

  • Li J, Hoene M, Zhao X, et al. Stable isotope-assisted lipidomics combined with nontargeted isotopomer filtering, a tool to unravel the complex dynamics of lipid metabolism. Anal Chem. 2013b;85(9):4651–7.

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Chen Y, Momin A, et al. Elevation of sulfatides in ovarian cancer: an integrated transcriptomic and lipidomic analysis including tissue-imaging mass spectrometry. Mol Cancer. 2010;9:186.

    Article  PubMed Central  PubMed  Google Scholar 

  • Llorente A, Skotland T, Sylvanne T, et al. Molecular lipidomics of exosomes released by PC-3 prostate cancer cells. Biochim Biophys Acta. 2013;1831(7):1302–9.

    Article  CAS  PubMed  Google Scholar 

  • Makarov A, Denisov E, Kholomeev A, et al. Performance evaluation of a hybrid linear ion trap/orbitrap mass spectrometer. Anal Chem. 2006;78(7):2113–20.

    Article  CAS  PubMed  Google Scholar 

  • Masoodi M, Eiden M, Koulman A, Spaner D, Volmer DA. Comprehensive lipidomics analysis of bioactive lipids in complex regulatory networks. Anal Chem. 2010;82(19):8176–85.

    Article  CAS  PubMed  Google Scholar 

  • 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(5):1137–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • McEvoy J, Baillie RA, Zhu H, et al. Lipidomics reveals early metabolic changes in subjects with schizophrenia: effects of atypical antipsychotics. PLoS One. 2013;8(7):e68717.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • McLaren DG, He T, Wang SP, et al. The use of stable-isotopically labeled oleic acid to interrogate lipid assembly in vivo: assessing pharmacological effects in preclinical species. J Lipid Res. 2011;52(6):1150–61.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Min HK, Kong G, Moon MH. Quantitative analysis of urinary phospholipids found in patients with breast cancer by nanoflow liquid chromatography-tandem mass spectrometry: II. Negative ion mode analysis of four phospholipid classes. Anal Bioanal Chem. 2010;396(3):1273–80.

    Article  CAS  PubMed  Google Scholar 

  • Min HK, Lim S, Chung BC, Moon MH. Shotgun lipidomics for candidate biomarkers of urinary phospholipids in prostate cancer. Anal Bioanal Chem. 2011;399(2):823–30.

    Article  CAS  PubMed  Google Scholar 

  • Murphy RC, Hankin JA, Barkley RM. Imaging of lipid species by MALDI mass spectrometry. J Lipid Res. 2009;50(Suppl):S317–22.

    PubMed Central  PubMed  Google Scholar 

  • Ollero M, Astarita G, Guerrera IC, et al. Plasma lipidomics reveals potential prognostic signatures within a cohort of cystic fibrosis patients. J Lipid Res. 2011;52(5):1011–22.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Oresic M. Informatics and computational strategies for the study of lipids. Biochim Biophys Acta. 2011;1811(11):991–9.

    Article  CAS  PubMed  Google Scholar 

  • Patterson AD, Maurhofer O, Beyoglu D, et al. Aberrant lipid metabolism in hepatocellular carcinoma revealed by plasma metabolomics and lipid profiling. Cancer Res. 2011;71(21):6590–600.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Piomelli D, Astarita G, Rapaka R. A neuroscientist’s guide to lipidomics. Nat Rev Neurosci. 2007;8(10):743–54.

    Article  CAS  PubMed  Google Scholar 

  • Rappley I, Myers DS, Milne SB, et al. Lipidomic profiling in mouse brain reveals differences between ages and genders, with smaller changes associated with alpha-synuclein genotype. J Neurochem. 2009;111(1):15–25.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rhee EP, Cheng S, Larson MG, et al. Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans. J Clin Invest. 2011;121(4):1402–11.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sampaio JL, Gerl MJ, Klose C, et al. Membrane lipidome of an epithelial cell line. Proc Natl Acad Sci U S A. 2011;108(5):1903–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Santos CR, Schulze A. Lipid metabolism in cancer. FEBS J. 2012;279(15):2610–23.

    Article  CAS  PubMed  Google Scholar 

  • Sato Y, Bernier F, Suzuki I, Kotani S, Nakagawa M, Oda Y. Comparative lipidomics of mouse brain exposed to enriched environment. J Lipid Res. 2013;54(10):2687–96.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Schuhmann K, Herzog R, Schwudke D, Metelmann-Strupat W, Bornstein SR, Shevchenko A. Bottom-up shotgun lipidomics by higher energy collisional dissociation on LTQ Orbitrap mass spectrometers. Anal Chem. 2011;83(14):5480–7.

    Article  CAS  PubMed  Google Scholar 

  • Schwudke D, Hannich JT, Surendranath V, et al. Top-down lipidomic screens by multivariate analysis of high-resolution survey mass spectra. Anal Chem. 2007;79(11):4083–93.

    Article  CAS  PubMed  Google Scholar 

  • Smilowitz JT, Zivkovic AM, Wan YJ, et al. Nutritional lipidomics: molecular metabolism, analytics, and diagnostics. Mol Nutr Food Res. 2013;57(8):1319–35.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Song J, Liu X, Wu J, et al. A highly efficient, high-throughput lipidomics platform for the quantitative detection of eicosanoids in human whole blood. Anal Biochem. 2013;433(2):181–8.

    Article  CAS  PubMed  Google Scholar 

  • Taguchi R, Ishikawa M. Precise and global identification of phospholipid molecular species by an Orbitrap mass spectrometer and automated search engine Lipid Search. J Chromatogr A. 2010;1217(25):4229–39.

    Article  CAS  PubMed  Google Scholar 

  • Vilella F, Ramirez LB, Simon C. Lipidomics as an emerging tool to predict endometrial receptivity. Fertil Steril. 2013;99(4):1100–6.

    Article  CAS  PubMed  Google Scholar 

  • Wang M, Fang H, Han X. Shotgun lipidomics analysis of 4-hydroxyalkenal species directly from lipid extracts after one-step in situ derivatization. Anal Chem. 2012;84(10):4580–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wei H, Hu C, Wang M, et al. Lipidomics reveals multiple pathway effects of a multi-components preparation on lipid biochemistry in ApoE*3Leiden.CETP mice. PLoS One. 2012;7(1):e30332.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wenk MR. The emerging field of lipidomics. Nat Rev Drug Discov. 2005;4(7):594–610.

    Article  CAS  PubMed  Google Scholar 

  • Wenk MR. Lipidomics in drug and biomarker development. Expert Opin Drug Discov. 2006;1(7):723–36.

    Article  CAS  PubMed  Google Scholar 

  • Wolf C, Quinn PJ. Lipidomics: practical aspects and applications. Prog Lipid Res. 2008;47(1):15–36.

    Article  CAS  PubMed  Google Scholar 

  • Yang K, Cheng H, Gross RW, Han X. Automated lipid identification and quantification by multidimensional mass spectrometry-based shotgun lipidomics. Anal Chem. 2009;81(11):4356–68.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yang K, Dilthey BG, Gross RW. Identification and quantitation of fatty acid double bond positional isomers: a shotgun lipidomics approach using charge-switch derivatization. Anal Chem. 2013;85(20):9742–50.

    Article  CAS  PubMed  Google Scholar 

  • Zhao C, Mao J, Ai J, et al. Integrated lipidomics and transcriptomic analysis of peripheral blood reveals significantly enriched pathways in type 2 diabetes mellitus. BMC Med Genomics. 2013;6 Suppl 1:S12.

    PubMed Central  PubMed  Google Scholar 

  • Zhou X, Mao J, Ai J, et al. Identification of plasma lipid biomarkers for prostate cancer by lipidomics and bioinformatics. PLoS One. 2012;7(11):e48889.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, 116023, Dalian, China

    Chunxiu Hu, Jia Li & Guowang Xu

Authors
  1. Chunxiu Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jia Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guowang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guowang Xu .

Editor information

Editors and Affiliations

  1. Diabetes & Nutritional Sciences Division, King's College, London, United Kingdom

    Victor R. Preedy

  2. Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, London, United Kingdom

    Vinood B. Patel

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this entry

Cite this entry

Hu, C., Li, J., Xu, G. (2014). Mass Spectrometry-Based Lipidomics for Biomarker Research. In: Preedy, V., Patel, V. (eds) General Methods in Biomarker Research and their Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7740-8_36-1

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-7740-8_36-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Online ISBN: 978-94-007-7740-8

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation