Metabolomics as a tool for cardiac research

Nature Reviews Cardiology

Volumn 8, Issue 11, 2011, Pages 630-643

  Griffin, Julian L ^a   Atherton, Helen ^b   Shockcor, John ^b   Atzori, Luigi ^c  

^a MRC HUMAN NUTRITION RESEARCH   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c UNIVERSITY OF CAGLIARI   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; LIPID; LIPOPROTEIN;

ATHEROSCLEROSIS; CORONARY ARTERY DISEASE; DIABETIC CARDIOMYOPATHY; DISEASE COURSE; DNA DAMAGE; DNA MODIFICATION; FLUORESCENCE SPECTROSCOPY; FUNCTIONAL GENOMICS; HEART DISEASE; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HUMAN; INFRARED SPECTROSCOPY; LIPID METABOLISM; LIPIDOMICS; LIQUID CHROMATOGRAPHY; MASS FRAGMENTOGRAPHY; MASS SPECTROMETRY; MEDICAL RESEARCH; METABOLOMICS; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; PROTEOMICS; REVIEW; SENSITIVITY AND SPECIFICITY; TOXICITY TESTING;

BIOLOGICAL MARKERS; BIOMEDICAL TECHNOLOGY; CARDIOVASCULAR DISEASES; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; MASS SPECTROMETRY; METABOLIC NETWORKS AND PATHWAYS;

EID: 80055026433     PISSN: 17595002     EISSN: 17595010     Source Type: Journal    
DOI: 10.1038/nrcardio.2011.138     Document Type: Review

References (105)

1. Oliver, S.G., Winson, M.K., Kell, D.B. & Baganz, F. Systematic functional analysis of the yeast genome. Trends Biotechnol. 16, 373-378 (1998). (Pubitemid 28410425)
2. Tweeddale, H., Notley-McRobb, L. & Ferenci, T. Effect of slow growth on metabolism of Escherichia coli, as revealed by global metabolite pool ("metabolome") analysis. J. Bacteriol. 180, 5109-5116 (1998). (Pubitemid 28470937)
3. Nicholson, J.K., Lindon, J.C. & Holmes, E. 'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica 29, 1181-1189 (1999).
4. Wishart, D.S. et al. HMDB: a knowledgebase for the human metabolome. Nucleic Acids Res. 37, D603-D610 (2009).
5. Wishart, D.S. et al. HMDB: the Human Metabolome Database. Nucleic Acids Res. 35, D521-D526 (2007). (Pubitemid 46056263)
6. Goodacre, R., Vaidyanathan, S., Dunn, W.B., Harrigan, G.G. & Kell, D.B. Metabolomics by numbers: acquiring and understanding global metabolite data. Trends Biotechnol. 22, 245-252 (2004). (Pubitemid 38515742)
7. Griffin, J.L. The Cinderella story of metabolic profiling: does metabolomics get to go to the functional genomics ball? Philos. Trans. R. Soc. Lond. B. Biol. Sci. 361, 147-161 (2006). (Pubitemid 44858949)
8. Ellis, D.I., Dunn, W.B., Griffin, J.L., Allwood, J.W. & Goodacre, R. Metabolic fingerprinting as a diagnostic tool. Pharmacogenomics 8, 1243-1266 (2007). (Pubitemid 47578232)
9. German, J.B., Gillies, L.A., Smilowitz, J.T., Zivkovic, A.M. & Watkins, S.M. Lipidomics and lipid profiling in metabolomics. Curr. Opin. Lipidol. 18, 66-71 (2007). (Pubitemid 46090240)
10. Dunn, W.B., Broadhurst, D.I., Atherton, H.J., Goodacre, R. & Griffin, J.L. Systems level studies of mammalian metabolomes: the roles of mass spectrometry and nuclear magnetic resonance spectroscopy. Chem. Soc. Rev. 40, 387-426 (2011).
11. Atherton, H.J. et al. A combined 1H-NMR spectroscopy-and mass spectrometry-based metabolomic study of the PPARα null mutant mouse defines profound systemic changes in metabolism linked to the metabolic syndrome. Physiol. Genomics 27, 178-186 (2006). (Pubitemid 46702031)
12. Roberts, L.D. et al. Increased hepatic oxidative metabolism distinguishes the action of peroxisome proliferator-activated receptorδ from peroxisome proliferator-activated receptorγ in the ob/ob mouse. Genome Med. 1, 115 (2009).
13. Bothwell, J.H. & Griffin, J.L. An introduction to biological nuclear magnetic resonance spectroscopy. Biol. Rev. Camb. Philos. Soc. 86, 493-510 (2011).
14. Gadian, D.G. et al. Phosphorus nuclear magnetic resonance studies on normoxic and ischemic cardiac tissue. Proc. Natl Acad. Sci. USA 73, 4446-4448 (1976). (Pubitemid 8013915)
15. Ackerman, J.J., Bore, P.J., Gadian, D.G., Grove, T.H. & Radda, G.K. NMR studies of metabolism in perfused organs. Philos. Trans. R. Soc. Lond. B Biol. Sci. 289, 425-436 (1980).
16. Bailey, I.A., Williams, S.R., Radda, G.K. & Gadian, D.G. Activity of phosphorylase in total global ischaemia in the rat heart. A phosphorus 31 nuclear-magnetic-resonance study. Biochem. J. 196, 171-178 (1981). (Pubitemid 11079496)
17. Nunnally, R.L. & Hollis, D.P. Adenosine triphosphate compartmentation in living hearts: a phosphorus nuclear magnetic resonance saturation transfer study. Biochemistry 18, 3642-3646 (1979). (Pubitemid 9255099)
18. Orchard, C.H., Allen, D.G. & Morris, P.G. The role of intracellular [Ca2+] and [H+] in contractile failure of the hypoxic heart. Adv. Myocardiol. 6, 417-427 (1985).
19. Kusuoka, H., Weisfeldt, M.L., Zweier, J.L., Jacobus, W.E. & Marban, E. Mechanism of early contractile failure during hypoxia in intact ferret heart: evidence for modulation of maximal Ca2+-activated force by inorganic phosphate. Circ. Res. 59, 270-282 (1986). (Pubitemid 17178121)
20. Yoshiyama, M. et al. 31P-MRS study of bio-energy recovering phenomenon. Biochem. Biophys. Res. Commun. 151, 865-871 (1988).
21. Bernard, M. et al. Cardioplegic arrest superimposed on evolving myocardial ischemia. Improved recovery after inhibition of hydroxyl radical generation by peroxidase or deferoxamine. A 31P nuclear resonance study. Circulation 78, 164-172 (1988).
22. Chatham, J.C., Seymour, A.L., Harmsen, E. & Radda, G.K. Depletion of myocardial glutathione: its effects on heart function and metabolism during ischaemia and reperfusion. Cardiovasc. Res. 22, 833-839 (1988). (Pubitemid 18268713)
23. Pieper, G.M., Salhany, J.M., Murray, W.J., Wu, S.T. & Eliot, R.S. Abnormal phosphocreatine metabolism in perfused diabetic hearts. A 31P nuclear-magnetic-resonance study. Biochem. J. 210, 477-481 (1983). (Pubitemid 13124440)
24. Matsumoto, Y., Kaneko, M., Kobayashi, A., Fujise, Y. & Yamazaki, N. Creatine kinase kinetics in diabetic cardiomyopathy. Am. J. Physiol. Endocrinol. Metab. 268, E1070-E1076 (1995).
25. Bailey, I.A., Gadian, D.G., Matthews, P.M., Radda, G.K. & Seeley, P.J. Studies of metabolism in the isolated, perfused rat heart using 13C NMR. FEBS Lett. 123, 315-318 (1981). (Pubitemid 11148767)
26. Neurohr, K.J., Barrett, E.J. & Shulman, R.G. Invivo carbon13 nuclear magnetic resonance studies of heart metabolism. Proc. Natl Acad. Sci. USA 80, 1603-1607 (1983). (Pubitemid 13052458)
27. Lewandowski, E.D. et al. Altered metabolite exchange between subcellular compartments in intact postischemic rabbit hearts. Circ. Res. 81, 165-175 (1997).
28. Griffin, J.L., O'Donnell, J.M., White, L.T., Hajjar, R.J. & Lewandowski, E.D. Postnatal expression and activity of the mitochondrial 2 oxoglutarate-malate carrier in intact hearts. Am. J. Physiol. Cell Physiol. 279, C1704-C1709 (2000).
29. Merritt, M.E. et al. Hyperpolarized 13C allows a direct measure of flux through a single enzyme-catalyzed step by NMR. Proc. Natl Acad. Sci. USA 104, 19773-19777 (2007).
30. Schroeder, M.A. et al. Real-time assessment of Krebs cycle metabolism using hyperpolarized 13C magnetic resonance spectroscopy. FASEB J. 23, 2529-2538 (2009).
31. Behar, K.L., Rothman, D.L., Shulman, R.G., Petroff, O.A. & Prichard, J.W. Detection of cerebral lactate invivo during hypoxemia by 1HNMR at relatively low field strengths (1.9 T). Proc. Natl Acad. Sci. USA 81, 2517-2519 (1984).
32. Reeves, R.C., Evanochko, W.T., Canby, R.C., McMillin, J.B. & Pohost, G.M. Demonstration of increased myocardial lipid with postischemic dysfunction ("myocardial stunning") by proton nuclear magnetic resonance spectroscopy. J. Am. Coll. Cardiol. 13, 739-744 (1989). (Pubitemid 19073943)
33. Haraguchi, S.I., Toshima, H., Matsumoto, I., Kuhara, T. & Shinka, T. Changes of organic acids in rat heart muscle under ischemic-like conditions. J. Chromatogr. 227, 1-9 (1982). (Pubitemid 12154733)
34. Haraguchi, S. et al. Analysis of organic acids in the hearts of patients with idiopathic cardiomyopathy by gas chromatography-mass spectrometry. J. Chromatogr. 230, 7-14 (1982). (Pubitemid 12012552)
35. Neese, R.A., Gertz, E.W., Wisneski, J.A., Gruenke, L.D. & Craig, J.C. A stable isotope technique for investigating lactate metabolism in humans. Biomed. Mass Spectrom. 10, 458-462 (1983). (Pubitemid 13016423)
36. Fiehn, O. et al. Metabolite profiling for plant functional genomics. Nat. Biotechnol. 18, 1157-1161 (2000).
37. Shellie, R.A. et al. Statistical methods for comparing comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry results: metabolomic analysis of mouse tissue extracts. J. Chromatogr. A. 1086, 83-90 (2005). (Pubitemid 41033272)
38. Fenn, J.B., Mann, M., Meng, C.K., Wong, S.F. & Whitehouse, C.M. Electrospray ionization for mass spectrometry of large biomolecules. Science 246, 64-71 (1989). (Pubitemid 19252085)
39. Laaksonen, R. et al. A systems biology strategy reveals biological pathways and plasma biomarker candidates for potentially toxic statin-induced changes in muscle. PLoS ONE 1, e97 (2006).
40. Pietiläinen, K.H. et al. Acquired obesity is associated with changes in the serum lipidomic profile independent of genetic effects-a monozygotic twin study. PLoS ONE 2, e218 (2007).
41. Han, X. & Gross, R.W. 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 (2005). (Pubitemid 40665798)
42. Han, X., Yang, K., Cheng, H., Fikes, K.N. & Gross, R.W. Shotgun lipidomics of phosphoethanolamine-containing lipids in biological samples after one-step insitu derivatization. J. Lipid Res. 46, 1548-1560 (2005). (Pubitemid 43109820)
43. Mayr, M. et al. Proteomic and metabolomic analysis of cardioprotection: Interplay between protein kinase C epsilon and delta in regulating glucose metabolism of murine hearts. J. Mol. Cell Cardiol. 46, 268-277 (2009).
44. Griffin, J.L. et al. Metabolic profiling of genetic disorders: a multitissue 1H nuclear magnetic resonance spectroscopic and pattern recognition study into dystrophic tissue. Anal. Biochem. 293, 16-21 (2001). (Pubitemid 32500500)
45. Griffin, J.L., Williams, H.J., Sang, E. & Nicholson, J.K. Abnormal lipid profile of dystrophic cardiac tissue as demonstrated by one-and two-dimensional magic-angle spinning 1H NMR spectroscopy. Magn. Reson. Med. 46, 249-255 (2001). (Pubitemid 32703269)
46. Gulston, M.K. et al. A combined metabolomic and proteomic investigation of the effects of a failure to express dystrophin in the mouse heart. J. Proteome Res. 7, 2069-2077 (2008).
47. McIntosh, L., Granberg, K.E., Brière, K.M. & Anderson, J.E. Nuclear magnetic resonance spectroscopy study of muscle growth, mdx dystrophy and glucocorticoid treatments: correlation with repair. NMR Biomed. 11, 1-10 (1998). (Pubitemid 28164843)
48. McIntosh, L.M., Garrett, K.L., Megeney, L., Rudnicki, M.A. & Anderson, J.E. Regeneration and myogenic cell proliferation correlate with taurine levels in dystrophin-and MyoD-deficient muscles. Anat. Rec. 252, 311-324 (1998). (Pubitemid 28440916)
49. Griffin, J.L., Sang, E., Evens, T., Davies, K. & Clarke, K. Metabolic profiles of dystrophin and utrophin expression in mouse models of Duchenne muscular dystrophy. FEBS Lett. 530, 109-116 (2002). (Pubitemid 35248195)
50. Khairallah, M. et al. Metabolic and signaling alterations in dystrophin-deficient hearts precede overt cardiomyopathy. J. Mol. Cell Cardiol. 43, 119-129 (2007). (Pubitemid 47069387)
51. Griffin, J.L. & Des Rosiers, C. Applications of metabolomics and proteomics to the mdx mouse model of Duchenne muscular dystrophy: lessons from downstream of the transcriptome. Genome Med. 1, 32 (2009).
52. Kao, H.J. et al. ENU mutagenesis identifies mice with cardiac fibrosis and hepatic steatosis caused by a mutation in the mitochondrial trifunctional proteinβ subunit. Hum. Mol. Genet. 15, 3569-3577 (2006).
53. Karpanen, T. et al. Overexpression of vascular endothelial growth factorB in mouse heart alters cardiac lipid metabolism and induces myocardial hypertrophy. Circ. Res. 103, 1018-1026 (2008).
54. Mervaala, E. et al. Metabolomics in angiotensinII-induced cardiac hypertrophy. Hypertension 55, 508-515 (2010).
55. Alexander, D., Lombardi, R., Rodriguez, G., Mitchell, M.M. & Marian, A.J. Metabolomic distinction and insights into the pathogenesis of human primary dilated cardiomyopathy. Eur. J. Clin. Invest. 41, 527-538 (2010).
56. Lee, S.S. et al. Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol. Cell Biol. 15, 3012-3022 (1995).
57. Gélinas, R. et al. Alterations in carbohydrate metabolism and its regulation in PPARα null mouse hearts. Am. J. Physiol. Heart Circ. Physiol. 294, H1571-H1580 (2008). (Pubitemid 351490586)
58. Atherton, H.J. et al. Metabolomics of the interaction between PPAR-α and age in the PPAR-α-null mouse. Mol. Syst. Biol. 5, 259 (2009).
59. Wheelock, C.E., Goto, S., Hammock, B.D. & Newman, J.W. Clofibrate-induced changes in the liver, heart, brain and white adipose lipid metabolome of Swiss-Webster mice. Metabolomics 3, 137-145 (2007). (Pubitemid 46863868)
60. Akki, A., Smith, K. & Seymour, A.M. Compensated cardiac hypertrophy is characterised by a decline in palmitate oxidation. Mol. Cell Biochem. 311, 215-224 (2008).
61. O'Donnell, J.M., Fields, A.D., Sorokina, N. & Lewandowski, E.D. The absence of endogenous lipid oxidation in early stage heart failure exposes limits in lipid storage and turnover. J. Mol. Cell Cardiol. 44, 315-322 (2008).
62. Sorokina, N. et al. Recruitment of compensatory pathways to sustain oxidative flux with reduced carnitine palmitoyltransferaseI activity characterizes inefficiency in energy metabolism in hypertrophied hearts. Circulation 115, 2033-2041 (2007). (Pubitemid 46625954)
63. Perrine, S.A. et al. Cardiac effects of MDMA on the metabolic profile determined with 1H-magnetic resonance spectroscopy in the rat. NMR Biomed. 22, 419-425 (2009).
64. Andreadou, I. et al. Metabonomic identification of novel biomarkers in doxorubicin cardiotoxicity and protective effect of the natural antioxidant oleuropein. NMR Biomed. 22, 585-592 (2009).
65. Clish, CB. et al. Integrative biological analysis of the APOE*3-Leiden transgenic mouse. OMICS 8, 3-13 (2004). (Pubitemid 38481151)
66. Kleemann, R. et al. Atherosclerosis and liver inflammation induced by increased dietary cholesterol intake: a combined transcriptomics and metabolomics analysis. Genome Biol. 8, R200 (2007).
67. Mayr, M. et al. Proteomic and metabolomic analyses of atherosclerotic vessels from apolipoprotein E-deficient mice reveal alterations in inflammation, oxidative stress and energy metabolism. Arterioscler. Thromb. Vasc. Biol. 25, 2135-2142 (2005). (Pubitemid 41416312)
68. Martin, J.C. et al. 1HNMR metabonomics can differentiate the early atherogenic effect of dairy products in hyperlipidemic hamsters. Atherosclerosis 206, 123-133 (2009).
69. Cheng, KK. et al. A metabolomic study of the LDL receptor null mouse fed a high-fat diet reveals profound perturbations in choline metabolism that are shared with ApoE null mice. Physiol. Genomics 41, 224-231 (2010).
70. Mercer, J.R. et al. DNA damage links mitochondrial dysfunction to atherosclerosis and the metabolic syndrome. Circ. Res. 107, 1021-1031 (2010).
71. Wang, Z. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472, 57-63 (2011).
72. Wheelock, C.E. et al. Systems biology approaches and pathway tools for investigating cardiovascular disease. Mol. Biosyst. 5, 588-602 (2009).
73. Goonewardena, S.N., Prevette, L.E. & Desai, A.A. Metabolomics and atherosclerosis. Curr. Atheroscler. Rep. 12, 267-272 (2010).
74. Waterman, C.L., Kian-Kai, C. & Griffin, J.L. Metabolomic strategies to study lipotoxicity in cardiovascular disease. Biochim. Biophys. Acta 1801, 230-234 (2010).
75. Brindle, J.T. et al. Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics. Nat. Med. 8, 1439-1444 (2002). (Pubitemid 36019430)
76. Brindle, J.T., Nicholson, J.K., Schofield, P.M., Grainger, D.J. & Holmes, E. Application of chemometrics to 1HNMR spectroscopic data to investigate a relationship between human serum metabolic profiles and hypertension. Analyst 128, 32-36 (2003). (Pubitemid 36140336)
77. Kirschenlohr, H.L. et al. Proton NMR analysis of plasma is a weak predictor of coronary artery disease. Nat. Med. 12, 705-710 (2006). (Pubitemid 43865242)
78. Roussel, R. et al. NMR-based prediction of cardiovascular risk in diabetes. Nat. Med. 13, 399-400 (2007). (Pubitemid 46559813)
79. Mora, S. et al. Lipoprotein particle size and concentration by nuclear magnetic resonance and incident type2 diabetes in women. Diabetes 59, 1153-1160 (2010).
80. Mäkinen, V.P. et al. 1HNMR metabonomics approach to the disease continuum of diabetic complications and premature death. Mol. Syst. Biol. 4, 167 (2008).
81. Würtz, P. et al. Characterization of systemic metabolic phenotypes associated with subclinical atherosclerosis. Mol. Biosyst. 7, 385-393 (2010).
82. Inouye, M. et al. Metabonomic, transcriptomic, and genomic variation of a population cohort. Mol. Syst. Biol. 6, 441 (2010).
83. de Mello, V.D. et al. Link between plasma ceramides, inflammation and insulin resistance: association with serum IL6 concentration in patients with coronary heart disease. Diabetologia 52, 2612-2615 (2009).
84. Gieger, C. et al. Genetics meets metabolomics: a genome-wide association study of metabolite profiles in human serum. PLoS Genet. 4, e1000282 (2008).
85. Teul, J. et al. Improving metabolite knowledge in stable atherosclerosis patients by association and correlation of GC-MS and 1HNMR fingerprints. J. Proteome Res. 8, 5580-5589 (2007).
86. Holmes, E. et al. Human metabolic phenotype diversity and its association with diet and blood pressure. Nature 453, 396-400 (2008). (Pubitemid 351693125)
87. Sabatine, M.S. et al. Metabolomic identification of novel biomarkers of myocardial ischemia. Circulation 112, 3868-3875 (2005). (Pubitemid 43739484)
88. Lewis, G.D. et al. Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury. J. Clin. Invest. 118, 3503-3512 (2008).
89. Li, N. et al. Beneficial effects of soluble epoxide hydrolase inhibitors in myocardial infarction model: Insight gained using metabolomic approaches. J. Mol. Cell Cardiol. 47, 835-845 (2009).
90. Dunn, W.B. et al. Serum metabolomics reveals many novel metabolic markers of heart failure, including pseudouridine and 2 oxoglutarate. Metabolomics 3, 413-426.
91. Sample, J., Cleland, J.G. & Seymour, A.M. Metabolic remodeling in the aging heart. J. Mol. Cell Cardiol. 40, 56-63 (2006). (Pubitemid 43012117)
92. Smith, C.S., Bottomley, P.A., Schulman, S.P., Gerstenblith, G., Weiss, R.G. Altered creatine kinase adenosine triphosphate kinetics in failing hypertrophied human myocardium. Circulation 114, 1151-1158 (2006). (Pubitemid 44386479)
93. Merritt, M.E., Harrison, C., Storey, C., Sherry, A.D. & Malloy, C.R. Inhibition of carbohydrate oxidation during the first minute of reperfusion after brief ischemia: NMR detection of hyperpolarized 13CO2 and H13CO3-. Magn. Reson. Med. 60, 1029-1036 (2008).
94. Lewandowski, E.D. & Johnston, D.L. Reduced substrate oxidation in postischemic myocardium: 13C and 31PNMR analyses. Am. J. Physiol. Heart Circ. Physiol. 258, H1357-H1365 (1990). (Pubitemid 20187201)
95. Lewandowski, E.D. & White, L.T. Pyruvate dehydrogenase influences postischemic heart function. Circulation 91, 2071-2079 (1995).
96. Kudej, R.K. et al. Brief increase in carbohydrate oxidation following reperfusion reverses myocardial stunning in conscious pigs. Circulation 106, 2836-2841 (2002). (Pubitemid 35396984)
97. Kannel, W.B., Hjortland, M. & Castelli, W.P. Role of diabetes in congestive heart failure: the Framingham study. Am. J. Cardiol. 34, 29-34 (1974).
98. Stratton, I.M. et al., Association of glycaemia with macrovascular and microvascular complications of type2 diabetes (UKPDS 35): prospective observational study. BMJ 321, 405-412 (2000). (Pubitemid 30609442)
99. McGavock, J.M. et al. Cardiac steatosis in diabetes mellitus: a 1H-magnetic resonance spectroscopy study. Circulation 116, 1170-1175 (2007). (Pubitemid 47360218)
100. Hankiewicz, J.H., Banke, N.H., Farjah, M., Lewandowski, E.D. Early impairment of transmural principal strains in the left ventricle wall following short-term, high fat feeding of mice predisposed to cardiac steatosis. Circ. Cardiovasc. Imaging 3, 710-717 (2010).
101. Watkins, S.M., Reifsnyder, P.R., Pan, H.J., German, J.B. & Leiter, E.H. Lipid metabolome-wide effects of the PPARγ agonist rosiglitazone. J. Lipid Res. 43, 1809-1817 (2002). (Pubitemid 35315798)
102. Su, X., Han, X., Mancuso, D.J., Abendschein, D.R. & Gross, R.W. Accumulation of long-chain acylcarnitine and 3hydroxy acylcarnitine molecular species in diabetic myocardium: identification of alterations in mitochondrial fatty acid processing in diabetic myocardium by shotgun lipidomics. Biochemistry 44, 5234-5245 (2005). (Pubitemid 40471236)
103. Han, X. et al. Shotgun lipidomics identifies cardiolipin depletion in diabetic myocardium linking altered substrate utilization with mitochondrial dysfunction. Biochemistry 44, 16684-16694 (2005). (Pubitemid 41832048)
104. Chatham, J.C., Gao, Z.P., Bonen, A. & Forder, J.R. Preferential inhibition of lactate oxidation relative to glucose oxidation in the rat heart following diabetes. Cardiovasc. Res. 43, 96-106 (1999). (Pubitemid 29322869)
105. O'Donnell, J.M. et al. Accelerated triacylglycerol turnover kinetics in hearts of diabetic rats include evidence for compartmented lipid storage. Am. J. Physiol. Endocrinol. Metab. 290, E448-E455 (2006). (Pubitemid 43671690)