Molecular and Cellular Biochemistry

, Volume 442, Issue 1–2, pp 187–201 | Cite as

Comprehensive analysis of phospholipids in the brain, heart, kidney, and liver: brain phospholipids are least enriched with polyunsaturated fatty acids

  • Jaewoo Choi
  • Tai Yin
  • Koichiro Shinozaki
  • Joshua W. Lampe
  • Jan F. Stevens
  • Lance B. Becker
  • Junhwan Kim


It is commonly accepted that brain phospholipids are highly enriched with long-chain polyunsaturated fatty acids (PUFAs). However, the evidence for this remains unclear. We used HPLC–MS to analyze the content and composition of phospholipids in rat brain and compared it to the heart, kidney, and liver. Phospholipids typically contain one PUFA, such as 18:2, 20:4, or 22:6, and one saturated fatty acid, such as 16:0 or 18:0. However, we found that brain phospholipids containing monounsaturated fatty acids in the place of PUFAs are highly elevated compared to phospholipids in the heart, kidney, and liver. The relative content of phospholipid containing PUFAs is ~ 60% in the brain, whereas it is over 90% in other tissues. The most abundant species of phosphatidylcholine (PC) is PC(16:0/18:1) in the brain, whereas PC(18:0/20:4) and PC(16:0/20:4) are predominated in other tissues. Moreover, several major species of plasmanyl and plasmenyl phosphatidylethanolamine are found to contain monounsaturated fatty acid in the brain only. Overall, our data clearly show that brain phospholipids are the least enriched with PUFAs of the four major organs, challenging the common belief that the brain is highly enriched with PUFAs.


HPLC–MS Brain lipids Monounsaturated fatty acid Cardiolipin 



We would like to acknowledge Dr. Edmund Miller for his comments and helpful advice in writing the manuscript. This work was supported by the National Institutes of Health [RO1HL067630 and S10RR027878].

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice where the studies were conducted.

Supplementary material

11010_2017_3203_MOESM1_ESM.pdf (469 kb)
Supplementary material 1 (PDF 468 kb)


  1. 1.
    Farooqui AA, Horrocks LA, Farooqui T (2007) Modulation of inflammation in brain: a matter of fat. J Neurochem 101:577–599. CrossRefPubMedGoogle Scholar
  2. 2.
    Miller LR, Jorgensen MJ, Kaplan JR, Seeds MC, Rahbar E, Morgan TM, Welborn A, Chilton SM, Gillis J, Hester A, Rukstalis M, Sergeant S, Chilton FH (2016) Alterations in levels and ratios of n-3 and n-6 polyunsaturated fatty acids in the temporal cortex and liver of vervet monkeys from birth to early adulthood. Physiol Behav 156:71–78. CrossRefPubMedGoogle Scholar
  3. 3.
    Shepro D (2005) Microvascular Research: Biology and Pathology. Elsevier Science & Technology BooksGoogle Scholar
  4. 4.
    Moore SA (2001) Polyunsaturated fatty acid synthesis and release by brain-derived cells in vitro. J Mol Neurosci 16:195–200; discussion 215-21.  10.1385/JMN:16:2-3:195
  5. 5.
    Srinivasan V, Pandi-Perumal SR, Cardinali DP, Poeggeler B, Hardeland R (2006) Melatonin in Alzheimer’s disease and other neurodegenerative disorders. Behav Brain Funct 2:15. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Noseworthy MD, Bray TM (1998) Effect of oxidative stress on brain damage detected by MRI and in vivo 31P-NMR. Free Radic Biol Med 24:942–951CrossRefPubMedGoogle Scholar
  7. 7.
    Friedman J (2011) Why is the nervous system vulnerable to oxidative stress? In: Gadoth N, Göbel HH (eds) Oxidative stress and free radical damage in neurology. Humana Press, Totowa, NJ, pp 19–27CrossRefGoogle Scholar
  8. 8.
    Rink C, Khanna S (2011) Significance of brain tissue oxygenation and the arachidonic acid cascade in stroke. Antioxid Redox Signal 14:1889–1903. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    van der Vusse GJ, Roemen TH, Prinzen FW, Coumans WA, Reneman RS (1982) Uptake and tissue content of fatty acids in dog myocardium under normoxic and ischemic conditions. Circ Res 50:538–546CrossRefPubMedGoogle Scholar
  10. 10.
    Bazinet RP, Laye S (2014) Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci 15:771–785. CrossRefPubMedGoogle Scholar
  11. 11.
    Angelini R, Vitale R, Patil VA, Cocco T, Ludwig B, Greenberg ML, Corcelli A (2012) Lipidomics of intact mitochondria by MALDI-TOF/MS. J Lipid Res 53:1417–1425. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ivanova PT, Cerda BA, Horn DM, Cohen JS, McLafferty FW, Brown HA (2001) Electrospray ionization mass spectrometry analysis of changes in phospholipids in RBL-2H3 mastocytoma cells during degranulation. Proc Natl Acad Sci USA 98:7152–7157. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Milne S, Ivanova P, Forrester J, Alex Brown H (2006) Lipidomics: an analysis of cellular lipids by ESI-MS. Methods 39:92–103. CrossRefPubMedGoogle Scholar
  14. 14.
    Mitchell TW, Buffenstein R, Hulbert AJ (2007) Membrane phospholipid composition may contribute to exceptional longevity of the naked mole-rat (Heterocephalus glaber): a comparative study using shotgun lipidomics. Exp Gerontol 42:1053–1062. CrossRefPubMedGoogle Scholar
  15. 15.
    Abdullah L, Evans JE, Ferguson S, Mouzon B, Montague H, Reed J, Crynen G, Emmerich T, Crocker M, Pelot R, Mullan M, Crawford F (2014) Lipidomic analyses identify injury-specific phospholipid changes 3 mo after traumatic brain injury. FASEB J. PubMedGoogle Scholar
  16. 16.
    Wang HY, Liu CB, Wu HW, Kuo JS (2010) Direct profiling of phospholipids and lysophospholipids in rat brain sections after ischemic stroke. Rapid Commun Mass Spectrom 24:2057–2064. CrossRefPubMedGoogle Scholar
  17. 17.
    Cifkova E, Holcapek M, Lisa M (2013) Nontargeted lipidomic characterization of porcine organs using hydrophilic interaction liquid chromatography and off-line two-dimensional liquid chromatography-electrospray ionization mass spectrometry. Lipids 48:915–928. CrossRefPubMedGoogle Scholar
  18. 18.
    Chen CT, Domenichiello AF, Trepanier MO, Liu Z, Masoodi M, Bazinet RP (2013) The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms. J Lipid Res 54:2410–2422. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Taha AY, Basselin M, Ramadan E, Modi HR, Rapoport SI, Cheon Y (2012) Altered lipid concentrations of liver, heart and plasma but not brain in HIV-1 transgenic rats. Prostaglandins Leukot Essent Fatty Acids 87:91–101. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ulmann L, Mimouni V, Roux S, Porsolt R, Poisson JP (2001) Brain and hippocampus fatty acid composition in phospholipid classes of aged-relative cognitive deficit rats. Prostaglandins Leukot Essent Fatty Acids 64:189–195. CrossRefPubMedGoogle Scholar
  21. 21.
    Szabo A, Mezes M, Romvari R, Febel H (2010) Allometric scaling of fatty acyl chains in fowl liver, lung and kidney, but not in brain phospholipids. Comp Biochem Physiol B: Biochem Mol Biol 155:301–308. CrossRefGoogle Scholar
  22. 22.
    O’Brien JS, Fillerup DL, Mead JF (1964) Quantification and fatty acid and fatty aldehyde composition of ethanolamine, choline, and serine glycerophosphatides in human cerebral grey and white matter. J Lipid Res 5:329–338PubMedGoogle Scholar
  23. 23.
    Kim J, Hoppel CL (2013) Comprehensive approach to the quantitative analysis of mitochondrial phospholipids by HPLC-MS. J Chromatogr B Analyt Technol Biomed Life Sci 912:105–114. CrossRefPubMedGoogle Scholar
  24. 24.
    Christiansen K (1975) Lipid extraction procedure for in vitro studies of glyceride synthesis with labeled fatty acids. Anal Biochem 66:93–99CrossRefPubMedGoogle Scholar
  25. 25.
    Hsu FF, Turk J (2007) Differentiation of 1-O-alk-1′-enyl-2-acyl and 1-O-alkyl-2-acyl glycerophospholipids by multiple-stage linear ion-trap mass spectrometry with electrospray ionization. J Am Soc Mass Spectrom 18:2065–2073. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Kim J, Lampe JW, Yin T, Shinozaki K, Becker LB (2015) Phospholipid alterations in the brain and heart in a rat model of asphyxia-induced cardiac arrest and cardiopulmonary bypass resuscitation. Mol Cell Biochem 408:273–281. CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Choi J, Leonard SW, Kasper K, McDougall M, Stevens JF, Tanguay RL, Traber MG (2015) Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain lysophospholipids discovered using lipidomics. J Lipid Res 56:1182–1190. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Kim J, Minkler PE, Salomon RG, Anderson VE, Hoppel CL (2011) Cardiolipin: characterization of distinct oxidized molecular species. J Lipid Res 52:125–135. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Qi K, Hall M, Deckelbaum RJ (2002) Long-chain polyunsaturated fatty acid accretion in brain. Curr Opin Clin Nutr Metab Care 5:133–138CrossRefPubMedGoogle Scholar
  30. 30.
    Almeida R, Berzina Z, Arnspang EC, Baumgart J, Vogt J, Nitsch R, Ejsing CS (2015) Quantitative spatial analysis of the mouse brain lipidome by pressurized liquid extraction surface analysis. Anal Chem 87:1749–1756. CrossRefPubMedGoogle Scholar
  31. 31.
    Bascoul-Colombo C, Guschina IA, Maskrey BH, Good M, O’Donnell VB, Harwood JL (2016) Dietary DHA supplementation causes selective changes in phospholipids from different brain regions in both wild type mice and the Tg2576 mouse model of Alzheimer’s disease. Biochim Biophys Acta 1861:524–537. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Esfahani BA-SM, Mirmoghtadaei M, Anaraki SB (2014) Oxidative stress and aging. In: Massoud A, Rezaei N (eds) Immunology of aging. Springer, Berlin Heidelberg, Berlin, Heidelberg, pp 323–338CrossRefGoogle Scholar
  33. 33.
    Miladinovic T, Nashed MG, Singh G (2015) Overview of glutamatergic dysregulation in central pathologies. Biomolecules 5:3112–3141. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Poureslami R, Raes K, Huyghebaert G, De Smet S (2010) Effects of diet, age and gender on the polyunsaturated fatty acid composition of broiler anatomical compartments. Br Poult Sci 51:81–91. CrossRefPubMedGoogle Scholar
  35. 35.
    Bohm M, Schultz S, Koussoroplis AM, Kainz MJ (2014) Tissue-specific fatty acids response to different diets in common carp (Cyprinus carpio L.). PLoS ONE 9:e94759. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Martinez M, Mougan I (1998) Fatty acid composition of human brain phospholipids during normal development. J Neurochem 71:2528–2533CrossRefPubMedGoogle Scholar
  37. 37.
    Igarashi M, Ma K, Gao F, Kim HW, Greenstein D, Rapoport SI, Rao JS (2010) Brain lipid concentrations in bipolar disorder. J Psychiatr Res 44:177–182. CrossRefPubMedGoogle Scholar
  38. 38.
    Petursdottir AL, Farr SA, Morley JE, Banks WA, Skuladottir GV (2007) Lipid peroxidation in brain during aging in the senescence-accelerated mouse (SAM). Neurobiol Aging 28:1170–1178. CrossRefPubMedGoogle Scholar
  39. 39.
    Zancanaro C, Bolner A, Righetti C (2001) NMR spectroscopic analysis of rat brain development: in vitro proton and carbon studies of whole tissue and its phospholipid fraction. Dev Neurosci 23:107–112.CrossRefPubMedGoogle Scholar
  40. 40.
    Sato Y, Nakamura T, Aoshima K, Oda Y (2010) Quantitative and wide-ranging profiling of phospholipids in human plasma by two-dimensional liquid chromatography/mass spectrometry. Anal Chem 82:9858–9864. CrossRefPubMedGoogle Scholar
  41. 41.
    Han X, Yang J, Cheng H, Yang K, Abendschein DR, Gross RW (2005) Shotgun lipidomics identifies cardiolipin depletion in diabetic myocardium linking altered substrate utilization with mitochondrial dysfunction. Biochemistry 44:16684–16694. CrossRefPubMedGoogle Scholar
  42. 42.
    Houjou T, Yamatani K, Imagawa M, Shimizu T, Taguchi R (2005) A shotgun tandem mass spectrometric analysis of phospholipids with normal-phase and/or reverse-phase liquid chromatography/electrospray ionization mass spectrometry. Rapid Commun Mass Spectrom 19:654–666. CrossRefPubMedGoogle Scholar
  43. 43.
    Maccarone AT, Duldig J, Mitchell TW, Blanksby SJ, Duchoslav E, Campbell JL (2014) Characterization of acyl chain position in unsaturated phosphatidylcholines using differential mobility-mass spectrometry. J Lipid Res 55:1668–1677. CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Claypool SM, Koehler CM (2012) The complexity of cardiolipin in health and disease. Trends Biochem Sci 37:32–41. CrossRefPubMedGoogle Scholar
  45. 45.
    Schlame M, Ren M, Xu Y, Greenberg ML, Haller I (2005) Molecular symmetry in mitochondrial cardiolipins. Chem Phys Lipids 138:38–49. CrossRefPubMedGoogle Scholar
  46. 46.
    Chicco AJ, Sparagna GC (2007) Role of cardiolipin alterations in mitochondrial dysfunction and disease. Am J Physiol Cell Physiol 292:C33–C44. CrossRefPubMedGoogle Scholar
  47. 47.
    McGee CD, Lieberman P, Greenwood CE (1996) Dietary fatty acid composition induces comparable changes in cardiolipin fatty acid profile of heart and brain mitochondria. Lipids 31:611–616CrossRefPubMedGoogle Scholar
  48. 48.
    Khairallah RJ, Kim J, O’Shea KM, O’Connell KA, Brown BH, Galvao T, Daneault C, Des Rosiers C, Polster BM, Hoppel CL, Stanley WC (2012) Improved mitochondrial function with diet-induced increase in either docosahexaenoic acid or arachidonic acid in membrane phospholipids. PLoS ONE 7:e34402. CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Aoun M, Fouret G, Michel F, Bonafos B, Ramos J, Cristol JP, Carbonneau MA, Coudray C, Feillet-Coudray C (2012) Dietary fatty acids modulate liver mitochondrial cardiolipin content and its fatty acid composition in rats with non alcoholic fatty liver disease. J Bioenerg Biomembr 44:439–452. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Linus Pauling InstituteOregon State UniversityCorvallisUSA
  2. 2.Department of Pharmaceutical SciencesOregon State UniversityCorvallisUSA
  3. 3.Department of Emergency MedicineFeinstein Institute for Medical Research, Northwell Health SystemManhassetUSA
  4. 4.Department of Molecular MedicineZucker School of Medicine at Hofstra/NorthwellHempsteadUSA
  5. 5.Department of Emergency MedicineZucker School of Medicine at Hofstra/NorthwellHempsteadUSA

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