Comprehensive analysis of phospholipids in the brain, heart, kidney, and liver: brain phospholipids are least enriched with polyunsaturated fatty acids
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.
KeywordsHPLC–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.
All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice where the studies were conducted.
- 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. https://doi.org/10.1016/j.physbeh.2015.12.009 CrossRefPubMedGoogle Scholar
- 3.Shepro D (2005) Microvascular Research: Biology and Pathology. Elsevier Science & Technology BooksGoogle Scholar
- 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
- 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. https://doi.org/10.1073/pnas.13119509898/13/7152 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1016/j.exger.2007.09.004 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1096/fj.14-258228 PubMedGoogle Scholar
- 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. https://doi.org/10.1007/s11745-013-3820-4 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1016/j.plefa.2012.07.006 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1016/j.jasms.2007.08.019 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1007/s11010-015-2505-0 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1194/jlr.M058941 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1016/j.bbalip.2016.03.005 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1016/j.neurobiolaging.2006.05.033 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1021/bi051908a CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1002/rcm.1836 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1194/jlr.M046995 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1371/journal.pone.0034402 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1007/s10863-012-9448-x CrossRefPubMedGoogle Scholar