Abstract
Easy ambient sonic-spray ionization mass spectrometry (EASI-MS) was used to interrogate the hepatic lipid profiles of hypertriglyceridemic and control normotriglyceridemic mice. The analyses of ex vivo complex lipid mixtures were made directly with EASI-MS without accompanying separation steps. Intense ions for phosphatidylcholines and triacylglycerols were observed in the positive ion mode whereas the spectra in the negative ion mode provided profiles of phosphatidylethanolamines and phosphatidylinositol. EASI-MS was coupled to high-performance thin-layer chromatography for analysis of free fatty acids. Fourier transform–ion cyclotron resonance–mass spectrometry was also employed to confirm the identity of the detected lipids. We demonstrated higher incorporation of oleic acid in phosphatidylcholine and triacylglycerol composition, higher relative abundance of arachidonic acid containing phosphatidylinositol, and overall distinct free fatty acid profile in the livers of genetic hypertriglyceridemic mice. We propose that these alterations in liver lipid composition are related to the higher tissue and body metabolic rates described in these hypertriglyceridemic mice.
Similar content being viewed by others
References
Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C (2004) Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 109:433–438
Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, Forlani G, Melchionda N (1999) Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 107:450–455
Reid AE (2001) Nonalcoholic steatohepatitis. Gastroenterology 121:710–723
Ito Y, Azrolan N, O’Connell A, Walsh A, Breslow JL (1990) Hypertriglyceridemia as a result of human apolipoprotein C-III gene expression in transgenic mice. Science 1249:790–793
Aalto-Setala K, Fisher EA, Chen X, Chajekshaul T, Hayek T, Zechner R et al (1992) Mechanism of hypertriglyceridemia in human apolipoprotein (apo) C-III transgenic mice: diminished very low density lipoprotein fractional catabolic rate associated with increased apoCIII and reduced apoE on the particles. J Clin Invest 90:1889–1900
De Silva HV, Lauer SJ, Wang J, Simonett WS, Weisgraber KH, Mahley RW et al (1994) Overexpression of human apolipoprotein C-III in transgenic mice results in accumulation of apolipoprotein B48 remnant that is corrected by excess apolipoprotein E. J Biol Chem 269:2324–2335
Alberici LC, Oliveira HC, Paim BA, Mantello CC, Augusto AC, Zecchin KG, Gurgueira SA, Kowaltowski AJ, Vercesi AE (2009) Mitochondrial ATP-sensitive K(+) channels as redox signals to liver mitochondria in response to hypertriglyceridemia. Free Radic Biol Med 47:1432–1439
Alberici LC, Oliveira HC, Bighetti EJ, de Faria EC, Degaspari GR, Souza CT, Vercesi AE (2003) Hypertriglyceridemia increases mitochondrial resting respiration and susceptibility to permeability transition. J Bioenerg Biomembr 35:451–457
Alberici LC, Oliveira HC, Patrício PR, Kowaltowski AJ, Vercesi AE (2006) Hyperlipidemic mice present enhanced catabolism and higher mitochondrial ATP-sensitive K + channel activity. Gastroenterology 131:1228–1234
Han X, Gross RW (2003) Global analyses of cellular lipidomes directly from crude extracts of biological samples by ESI mass spectrometry: a bridge to lipidomics. J Lipid Res 44:1071–1079
Han X, Gross RW (2005) Shotgun lipidomics: electrospray ionization mass spectrometric analysis and quantitation of cellular lipidomes directly from crude extracts of biological samples. Mass Spectrom Rev 24:367–412
Wenk MR (2005) The emerging field of lipidomics. Nat Rev Drug Discov 4:594–610
Christie WW (2009) Lipidomics—a personal view. Lipid Technology 21:58–60
Pulfer M, Murphy RC (2003) Electrospray mass spectrometry of phospholipids. Mass Spectrom Rev 22:332–364
Byrdwell WC (2001) Atmospheric pressure chemical ionization mass spectrometry for analysis of lipids. Lipids 36:327–346
Fuchs B, Schiller J (2009) Application of MALDI-TOF mass spectrometry in lipidomics. Eur J Lipid Sci Technol 111:83–98
Fuchs B, Schiller J, Süβ R, Zscharnack M, Bader A, Müller P, Schürenberg M, Becker M, Suckau D (2008) Analysis of stem cell lipids by offline HPTLC-MALDI-TOF MS. Anal Bional Chem 392:849–860
Touchstone JC (1995) Thin-layer chromatographic procedures for lipid separation. J Chromatogr B 671:169–195
Santos LS, Haddad R, Höehr NF, Pilli RA, Eberlin MN (2004) Fast screening of low molecular weight compounds by thin-layer chromatography and “on-spot” MALDI-TOF mass spectrometry. Anal Chem 76:2144–2147
Paglia G, Ifa DR, Wu C, Corso G, Cooks RG (2010) Desorption electrospray ionization mass spectrometry analysis of lipids after two-dimensional high-performance thin-layer chromatography partial separation. Anal Chem 82:1744–1750
Alberici RM, Simas CR, Sanvido GB, Romão W, Lalli PM, Benassi M, Cunha IBS, Eberlin MN (2010) Ambient mass spectrometry: bringing MS into the real world. Anal Bional Chem 398:265–294
Venter A, Neflieu M, Cooks RG (2008) Ambient desorption mass spectrometry. Trends Anal Chem 27:284–290
Harris GA, Nyadong L, Fernandez FM (2008) Recent developments in ambient ionization techniques for analytical mass spectrometry. Analyst 133:1297–1301
Van Berkel GJ, Pasilis SP, Ovchinnikova O (2008) Established and emerging atmospheric pressure surface sampling/ionization techniques for mass spectrometry. J Mass Spectrom 43:1161–1180
Haddad R, Sparrapan R, Eberlin MN (2006) Desorption sonic spray ionization for (high) voltage-free ambient mass spectrometry. Rapid Commun Mass Spectrom 20:2901–2905
Haddad R, Sparrapan R, Kotiaho T, Eberlin MN (2008) Easy ambient sonic-spray ionization-membrane interface mass spectrometry for direct analysis of solution constituents. Anal Chem 80:898–903
Haddad R, Milagres HMS, Catharino RR, Eberlin MN (2008) Easy ambient sonic-spray ionization mass spectrometry combined with thin-layer chromatography. Anal Chem 80:2744–2750
Eberlin LS, Abdelnur PV, Passero A, de Sá GF, Daroda RJ, Souza V, Eberlin MN (2009) Analysis of biodiesel and biodiesel–petrodiesel blends by high performance thin layer chromatography combined with easy ambient sonic-spray ionization mass spectrometry. Analyst 134:1652–1657
Walsh A, Azrolan N, Wang K, Marcigliano A, O’Connell A, Breslow JL (1993) Intestinal expression of the human apoA-I gene in transgenic mice is controlled by a DNA region 3′ to the gene in the promoter of the adjacent convergently transcribed apoC-III gene. J Lipid Res 34:617–623
Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917
Yang L, Bennett R, Strum J, Ellsworth BB, Hamilton D, Tomlinson M, Wolf RW, Housley M, Roberts BA, Welsh J, Jackson BJ, Wood SG, Banka CL, Thulin CD, Linford MR (2009) Screening phosphatidylcholine biomarkers in mouse liver extracts from a hypercholesterolemia study using ESI-MS and chemometrics. Anal Bioanal Chem 393:643–654
Dill AL, Ifa DR, Manicke NE, Ouyang Z, Cooks RG (2009) Mass spectrometric imaging of lipids using desorption electrospray ionization. J Chromatogr B Analyt Technol Biomed Life Sci 877:2883–2889
Dill AL, Ifa DR, Manicke NE, Costa AB, Ramos-Vara JA, Knapp DW, Cooks RG (2009) Lipid profiles of canine invasive transitional cell carcinoma of the urinary bladder and adjacent normal tissue by desorption electrospray ionization imaging mass spectrometry. Anal Chem 81:8758–8764
Wiseman JM, Puolitaival SM, Takáts Z, Cooks RG, Caprioli RM (2005) Mass spectrometric profiling of intact biological tissue by using desorption electrospray ionization. Angew Chem Int Ed Engl 44:7094–7097
Nelson DL, Cox MM (2004) Lehninger principles of biochemistry. Freeman, New York
Manincke NE, Wiseman JM, Ifa DR, Cooks RG (2008) Desorption electrospray ionization (DESI) mass spectrometry and tandem mass spectrometry (MS/MS) of phospholipids and sphingolipids: ionization, adduct formation, and fragmentation. J Am Soc Mass Spectrom 19:531–543
Neelands PJ, Clandinin MT (1983) Diet fat influences liver plasma-membrane lipid composition and glucagon-stimulated adenylate cyclase activity. Biochem J 212:573–583
Simas RC, Catharino RR, Cunha IBS, Cabral EC, Barrera-Arellano D, Eberlin MN, Alberici RM (2010) Instantaneous characterization of vegetable oils via TAG and FFA profiles by easy ambient sonic-spray ionization mass spectrometry. Analyst 135:738–744
Picariello G, Sacchi R, Addeo F (2007) (2007) One-step characterization of triacylglycerols from animal fat by Maldi-Tof MS. Eur J Lipid Sci Technol 109:511–524
Perona JS, Barrón LJ, Ruiz-Gutiérrez V (1998) Determination of rat liver triglycerides by gas-liquid chromatography and reversed-phase high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 706:173–179
Wolk A, Furuheim M, Vessby B (2001) Fatty acid composition of adipose tissue and serum lipids are valid biological markers of dairy fat intake in men. J Nutr 131:828–833
Wu Z, Palmquist L (1991) Synthesis and biohydrogenation of FA by ruminal microorganisms in vitro. J Dairy Sci 74:3035–3036
Puri P, Wiest MM, Cheung O, Mirshahi F, Sargeant C, Min HK, Contos MJ, Sterling RK, Fuchs M, Zhou H, Watkins SM, Sanyal AJ (2009) The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology 50:1827–1838
Puri P, Baillie RA, Wiest MM, Mirshahi F, Choudhury J, Cheung O, Sargeant C, Contos MJ, Sanyal AJ (2007) A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology 46:1081–1090
Wojtovich AP, Williams DM, Karcz MK, Lopes CM, Gray DA, Nehrke KW, Brookes PS (2010) A novel mitochondrial K(ATP) channel assay. Circ Res 106:1190–1196
Katragadda D, Batchu SN, Cho WJ, Chaudhary KR, Falck JR, Seubert JM (2009) Epoxyeicosatrienoic acids limit damage to mitochondrial function following stress in cardiac cells. J Mol Cell Cardiol 46:867–875
Acknowledgment
This study is supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Alberici, L.C., Oliveira, H.C.F., Catharino, R.R. et al. Distinct hepatic lipid profile of hypertriglyceridemic mice determined by easy ambient sonic-spray ionization mass spectrometry. Anal Bioanal Chem 401, 1651–1659 (2011). https://doi.org/10.1007/s00216-011-5208-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-011-5208-8