Complex Energy Metabolic Changes in Heart Failure With Preserved Ejection Fraction and Heart Failure With Reduced Ejection Fraction

Canadian Journal of Cardiology

Volumn 33, Issue 7, 2017, Pages 860-871

  De Jong, Kirstie A ^a   Lopaschuk, Gary D ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

FATTY ACID; GLUCOSE; ISOLEUCINE; KETONE BODY; LEUCINE; REACTIVE OXYGEN METABOLITE; VALINE;

AEROBIC METABOLISM; AMINO ACID METABOLISM; AUTOPHAGY; CARDIAC MUSCLE CELL; DISORDERS OF MITOCHONDRIAL FUNCTIONS; ENERGY METABOLISM; FATTY ACID METABOLISM; FATTY ACID OXIDATION; GLUCOSE METABOLISM; GLUCOSE OXIDATION; GLYCOLYSIS; HEART FAILURE WITH PRESERVED EJECTION FRACTION; HEART FAILURE WITH REDUCED EJECTION FRACTION; HEART MUSCLE METABOLISM; HUMAN; MITOCHONDRIAL BIOGENESIS; MITOCHONDRIAL RESPIRATION; MITOPHAGY; NONHUMAN; REVIEW; TRANSCRIPTION REGULATION; COMORBIDITY; DIABETES MELLITUS, TYPE 2; GLOBAL HEALTH; HEART FAILURE; HEART STROKE VOLUME; METABOLISM; OBESITY; PATHOPHYSIOLOGY; PHYSIOLOGY;

COMORBIDITY; DIABETES MELLITUS, TYPE 2; ENERGY METABOLISM; GLOBAL HEALTH; HEART FAILURE; HUMANS; OBESITY; STROKE VOLUME;

EID: 85020019417     PISSN: 0828282X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cjca.2017.03.009     Document Type: Review

References (116)

1. Kochanek KD, Xu J, Murphy SL, Minino AM, Kung HC. Deaths: final data for 2009. National vital statistics reports: from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System. Natl Vital Stat Rep 2011;60:1-116.
2. Mozaffarian, D., Benjamin, E.J., Go, A.S., et al. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation 133 (2016), e38–e360.
3. Owan, T.E., Hodge, D.O., Herges, R.M., et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 355 (2006), 251–259.
4. Bhatia, R.S., Tu, J.V., Lee, D.S., et al. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med 355 (2006), 260–269.
5. Steinberg, B.A., Zhao, X., Heidenreich, P.A., et al. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation 126 (2012), 65–75.
6. Nagueh, S.F., Smiseth, O.A., Appleton, C.P., et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 29 (2016), 277–314.
7. Massie, B.M., Carson, P.E., McMurray, J.J., et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 359 (2008), 2456–2467.
8. Yip, G.W., Wang, M., Wang, T., et al. The Hong Kong diastolic heart failure study: a randomised controlled trial of diuretics, irbesartan and ramipril on quality of life, exercise capacity, left ventricular global and regional function in heart failure with a normal ejection fraction. Heart 94 (2008), 573–580.
9. Kitzman, D.W., Hundley, W.G., Brubaker, P.H., et al. A randomized double-blind trial of enalapril in older patients with heart failure and preserved ejection fraction: effects on exercise tolerance and arterial distensibility. Circ Heart Fail 3 (2010), 477–485.
10. Stanley, W.C., Recchia, F.A., Lopaschuk, G.D., Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 85 (2005), 1093–1129.
11. Neubauer, S., Horn, M., Cramer, M., et al. Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy. Circulation 96 (1997), 2190–2196.
12. Kass, D.A., Solaro, R.J., Mechanisms and use of calcium-sensitizing agents in the failing heart. Circulation 113 (2006), 305–315.
13. Garcia-Menendez, L., Karamanlidis, G., Kolwicz, S., Tian, R., Substrain specific response to cardiac pressure overload in C57BL/6 mice. Am J Physiol Heart Circ Physiol 305 (2013), H397–H402.
14. Barrick, C.J., Dong, A., Waikel, R., et al. Parent-of-origin effects on cardiac response to pressure overload in mice. Am J Physiol Heart Circ Physiol 297 (2009), H1003–H1009.
15. Houser, S.R., Margulies, K.B., Murphy, A.M., et al. Animal models of heart failure. A scientific statement from the American Heart Association [erratum in 2012;111:e54] Circ Res 111 (2012), 131–150.
16. Hauton, D., Bennett, M.J., Evans, R.D., Utilisation of triacylglycerol and non-esterified fatty acid by the working rat heart: myocardial lipid substrate preference. Biochim Biophys Acta 1533 (2001), 99–109.
17. van der Vusse, G.J., van Bilsen, M., Glatz, J.F., Cardiac fatty acid uptake and transport in health and disease. Cardiovasc Res 45 (2000), 279–293.
18. Murthy, M.S., Pande, S.V., Malonyl-CoA binding site and the overt carnitine palmitoyltransferase activity reside on the opposite sides of the outer mitochondrial membrane. Proc Natl Acad Sci U S A 84 (1987), 378–382.
19. Paulson, D.J., Ward, K.M., Shug, A.L., Malonyl CoA inhibition of carnitine palmityltransferase in rat heart mitochondria. FEBS Lett 176 (1984), 381–384.
20. Saddik, M., Gamble, J., Witters, L.A., Lopaschuk, G.D., Acetyl-CoA carboxylase regulation of fatty acid oxidation in the heart. J Biol Chem 268 (1993), 25836–25845.
21. Aubert, G., Martin, O.J., Horton, J.L., et al. The failing heart relies on ketone bodies as a fuel. Circulation 133 (2016), 698–705.
22. Garland, P.B., Newsholme, E.A., Randle, P.J., Effect of fatty acids, ketone bodies, diabetes and starvation on pyruvate metabolism in rat heart and diaphragm muscle. Nature 195 (1962), 381–383.
23. Newsholme, E.A., Randle, P.J., Manchester, K.L., Inhibition of the phosphofructokinase reaction in perfused rat heart by respiration of ketone bodies, fatty acids and pyruvate. Nature 193 (1962), 270–271.
24. Jeffrey, F.M., Diczku, V., Sherry, A.D., Malloy, C.R., Substrate selection in the isolated working rat heart: effects of reperfusion, afterload, and concentration. Basic Res Cardiol 90 (1995), 388–396.
25. Hasselbaink, D.M., Glatz, J.F., Luiken, J.J., Roemen, T.H., Van der Vusse, G.J., Ketone bodies disturb fatty acid handling in isolated cardiomyocytes derived from control and diabetic rats. Biochem J 371 (2003), 753–760.
26. Tardif, A., Julien, N., Pelletier, A., et al. Chronic exposure to beta-hydroxybutyrate impairs insulin action in primary cultures of adult cardiomyocytes. Am J Physiol Endocrinol Metab 281 (2001), E1205–E1212.
27. Sweatt, A.J., Wood, M., Suryawan, A., et al. Branched-chain amino acid catabolism: unique segregation of pathway enzymes in organ systems and peripheral nerves. Am J Physiol Endocrinol Metab 286 (2004), E64–E76.
28. Donato, J. Jr., Pedrosa, R.G., Cruzat, V.F., Pires, I.S., Tirapegui, J., Effects of leucine supplementation on the body composition and protein status of rats submitted to food restriction. Nutrition 22 (2006), 520–527.
29. Zhang, Y., Guo, K., LeBlanc, R.E., et al. Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes 56 (2007), 1647–1654.
30. Newgard, C.B., An, J., Bain, J.R., et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab 9 (2009), 311–326.
31. Huffman, K.M., Shah, S.H., Stevens, R.D., et al. Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women. Diabetes Care 32 (2009), 1678–1683.
32. Tai, E.S., Tan, M.L., Stevens, R.D., et al. Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men. Diabetologia 53 (2010), 757–767.
33. Wang, T.J., Larson, M.G., Vasan, R.S., et al. Metabolite profiles and the risk of developing diabetes. Nat Med 17 (2011), 448–453.
34. Lopaschuk, G.D., Ussher, J.R., Folmes, C.D., Jaswal, J.S., Stanley, W.C., Myocardial fatty acid metabolism in health and disease. Physiol Rev 90 (2010), 207–258.
35. Dorn, G.W., Vega, R.B., Kelly, D.P., Mitochondrial biogenesis and dynamics in the developing and diseased heart. Genes Dev 29 (2015), 1981–1991.
36. Knowlton, A.A., Chen, L., Malik, Z.A., Heart failure and mitochondrial dysfunction: the role of mitochondrial fission/fusion abnormalities and new therapeutic strategies. J Cardiovasc Pharmacol 63 (2014), 196–206.
37. Song, M., Mihara, K., Chen, Y., Scorrano, L., Dorn, G.W., Mitochondrial fission and fusion factors reciprocally orchestrate mitophagic culling in mouse hearts and cultured fibroblasts. Cell Metab 21 (2015), 273–285.
38. Finck, B.N., Kelly, D.P., PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. J Clin Invest 116 (2006), 615–622.
39. Tsutsui, H., Kinugawa, S., Matsushima, S., Oxidative stress and heart failure. Am J Physiol Heart Circ Physiol 301 (2011), H2181–H2190.
40. Belch, J.J., Bridges, A.B., Scott, N., Chopra, M., Oxygen free radicals and congestive heart failure. Br Heart J 65 (1991), 245–248.
41. Recchia, F.A., McConnell, P.I., Bernstein, R.D., et al. Reduced nitric oxide production and altered myocardial metabolism during the decompensation of pacing-induced heart failure in the conscious dog. Circ Res 83 (1998), 969–979.
42. Hill, M.F., Singal, P.K., Right and left myocardial antioxidant responses during heart failure subsequent to myocardial infarction. Circulation 96 (1997), 2414–2420.
43. Mallat, Z., Philip, I., Lebret, M., et al. Elevated levels of 8-iso-prostaglandin f2alpha in pericardial fluid of patients with heart failure: a potential role for in vivo oxidant stress in ventricular dilatation and progression to heart failure. Circulation 97 (1998), 1536–1539.
44. Sugamura, K., Keaney, J.F., Reactive oxygen species in cardiovascular disease. Free Radic Biol Med 51 (2011), 978–992.
45. Shires, S.E., Gustafsson, Å.B., Mitophagy and heart failure. J Mol Med (Berl) 93 (2015), 253–262.
46. Fukushima, A., Milner, K., Gupta, A., Lopaschuk, G.D., Myocardial energy substrate metabolism in heart failure: from pathways to therapeutic targets. Curr Pharm Des 21 (2015), 3654–3664.
47. Diakos, N.A., Navankasattusas, S., Abel, E.D., et al. Evidence of glycolysis up-regulation and pyruvate mitochondrial oxidation mismatch during mechanical unloading of the failing human heart. Implications for cardiac reloading and conditioning. JACC Basic Transl Sci 1 (2016), 432–444.
48. Lei, B., Lionetti, V., Young, M.E., et al. Paradoxical downregulation of the glucose oxidation pathway despite enhanced flux in severe heart failure. J Mol Cell Cardiol 36 (2004), 567–576.
49. Witham, W., Yester, K., O'Donnell, C.P., McGaffin, K.R., Restoration of glucose metabolism in leptin-resistant mouse hearts after acute myocardial infarction through the activation of survival kinase pathways. J Mol Cell Cardiol 53 (2012), 91–100.
50. Masoud, W.G., Ussher, J.R., Wang, W., et al. Failing mouse hearts utilize energy inefficiently and benefit from improved coupling of glycolysis and glucose oxidation. Cardiovasc Res 101 (2014), 30–38.
51. Conceição, G., Heinonen, I., Lourenço, A.P., Duncker, D.J., Falcão-Pires, I., Animal models of heart failure with preserved ejection fraction. Neth Heart J 24 (2016), 275–286.
52. Peterson, L.R., Herrero, P., Schechtman, K.B., et al. Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation 109 (2004), 2191–2196.
53. Rijzewijk, L.J., van der Meer, R.W., Lamb, H.J., et al. Altered myocardial substrate metabolism and decreased diastolic function in nonischemic human diabetic cardiomyopathy: studies with cardiac positron emission tomography and magnetic resonance imaging. J Am Coll Cardiol 54 (2009), 1524–1532.
54. Davila-Roman, V.G., Vedala, G., Herrero, P., et al. Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy. J Am Coll Cardiol 40 (2002), 271–277.
55. Tuunanen, H., Engblom, E., Naum, A., et al. Free fatty acid depletion acutely decreases cardiac work and efficiency in cardiomyopathic heart failure. Circulation 114 (2006), 2130–2137.
56. Heather, L.C., Cole, M.A., Lygate, C.A., et al. Fatty acid transporter levels and palmitate oxidation rate correlate with ejection fraction in the infarcted rat heart. Cardiovasc Res 72 (2006), 430–437.
57. Mori, J., Basu, R., McLean, B.A., et al. Agonist-induced hypertrophy and diastolic dysfunction are associated with selective reduction in glucose oxidation. A metabolic contribution to heart failure with normal ejection fraction. Circ Heart Fail 5 (2012), 493–503.
58. Mori, J., Alrob, O.A., Wagg, C.S., et al. ANG II causes insulin resistance and induces cardiac metabolic switch and inefficiency: a critical role of PDK4. Am J Physiol Heart Circ Physiol 304 (2013), H1103–H1113.
59. Weitzel, L.B., Ambardekar, A.V., Brieke, A., et al. Left ventricular assist device effects on metabolic substrates in the failing heart. PLoS One, 8, 2013, e60292.
60. Zhang, L., Jaswal, J.S., Ussher, J.R., et al. Cardiac insulin-resistance and decreased mitochondrial energy production precede the development of systolic heart failure after pressure-overload hypertrophy. Circ Heart Fail 6 (2013), 1039–1048.
61. Zhabyeyev, P., Gandhi, M., Mori, J., et al. Pressure-overload-induced heart failure induces a selective reduction in glucose oxidation at physiological afterload. Cardiovasc Res 97 (2013), 676–685.
62. Moravec, J., El Alaoui-Talibi, Z., Moravec, M., Guendouz, A., Control of oxidative metabolism in volume-overloaded rat hearts. Ince, C., Kesecioglu, J., Telci, L., Akpir, K., (eds.) Oxygen Transport to Tissue XVII, 1996, Springer US, Boston, MA, 205–212.
63. Degens, H., de Brouwer, K.F., Gilde, A.J., et al. Cardiac fatty acid metabolism is preserved in the compensated hypertrophic rat heart. Basic Res Cardiol 101 (2006), 17–26.
64. Leong, H.S., Grist, M., Parsons, H., et al. Accelerated rates of glycolysis in the hypertrophied heart: are they a methodological artifact?. Am J Physiol Endocrinol Metab 282 (2002), E1039–E1045.
65. Funada, J., Betts, T.R., Hodson, L., et al. Substrate utilization by the failing human heart by direct quantification using arterio-venous blood sampling. PLoS One, 4, 2009, e7533.
66. Bedi, K.C. Jr., Snyder, N.W., Brandimarto, J., et al. Evidence for intramyocardial disruption of lipid metabolism and increased myocardial ketone utilization in advanced human heart failure. Circulation 133 (2016), 706–716.
67. Sun, H., Olson, K.C., Gao, C., et al. Catabolic defect of branched-chain amino acids promotes heart failure. Circulation 133 (2016), 2038–2049.
68. Wang, W., Zhang, F., Xia, Y., et al. Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction. Am J Physiol Heart Circ Physiol 311 (2016), H1160–H1169.
69. Grover-McKay, M., Schwaiger, M., Krivokapich, J., et al. Regional myocardial blood flow and metabolism at rest in mildly symptomatic patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 13 (1989), 317–324.
70. Rosenblatt-Velin, N., Montessuit, C., Papageorgiou, I., Terrand, J., Lerch, R., Postinfarction heart failure in rats is associated with upregulation of GLUT-1 and downregulation of genes of fatty acid metabolism. Cardiovasc Res 52 (2001), 407–416.
71. Kato, T., Niizuma, S., Inuzuka, Y., et al. Analysis of metabolic remodeling in compensated left ventricular hypertrophy and heart failure. Circ Heart Fail 3 (2010), 420–430.
72. Neglia, D., De Caterina, A., Marraccini, P., et al. Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 293 (2007), H3270–H3278.
73. Sack, M.N., Rader, T.A., Park, S., et al. Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. Circulation 94 (1996), 2837–2842.
74. Osorio, J.C., Stanley, W.C., Linke, A., et al. Impaired myocardial fatty acid oxidation and reduced protein expression of retinoid X receptor-alpha in pacing-induced heart failure. Circulation 106 (2002), 606–612.
75. Taylor, M., Wallhaus, T.R., Degrado, T.R., et al. An evaluation of myocardial fatty acid and glucose uptake using PET with [18F]fluoro-6-thia-heptadecanoic acid and [18F]FDG in patients with congestive heart failure. J Nucl Med 42 (2001), 55–62.
76. Gupte, A.A., Hamilton, D.J., Cordero-Reyes, A.M., et al. Mechanical unloading promotes myocardial energy recovery in human heart failure. Circ Cardiovasc Genet 7 (2014), 266–276.
77. Karbowska, J., Kochan, Z., Smolenski, R.T., Peroxisome proliferator-activated receptor alpha is downregulated in the failing human heart. Cell Mol Biol Lett 8 (2003), 49–53.
78. Schroeder, M.A., Lau, A.Z., Chen, A.P., et al. Hyperpolarized (13)C magnetic resonance reveals early- and late-onset changes to in vivo pyruvate metabolism in the failing heart. Eur J Heart Fail 15 (2013), 130–140.
79. Riehle, C., Wende, A.R., Zaha, V.G., et al. PGC-1beta deficiency accelerates the transition to heart failure in pressure overload hypertrophy. Circ Res 109 (2011), 783–793.
80. Du, Z., Shen, A., Huang, Y., et al. 1H-NMR-based metabolic analysis of human serum reveals novel markers of myocardial energy expenditure in heart failure patients. PLoS One, 9, 2014, e88102.
81. Lommi, J., Kupari, M., Koskinen, P., et al. Blood ketone bodies in congestive heart failure. J Am Coll Cardiol 28 (1996), 665–672.
82. Lommi, J., Koskinen, P., Naveri, H., Harkonen, M., Kupari, M., Heart failure ketosis. J Intern Med 242 (1997), 231–238.
83. Schugar, R.C., Moll, A.R., André d'Avignon, D., et al. Cardiomyocyte-specific deficiency of ketone body metabolism promotes accelerated pathological remodeling. Mol Metab 3 (2014), 754–769.
84. Ruiz-Canela, M., Toledo, E., Clish, C.B., et al. Plasma branched-chain amino acids and incident cardiovascular disease in the PREDIMED trial. Clin Chem 62 (2016), 582–592.
85. Magnusson, M., Lewis, G.D., Ericson, U., et al. A diabetes-predictive amino acid score and future cardiovascular disease. Eur Heart J 34 (2013), 1982–1989.
86. Bhattacharya, S., Granger, C.B., Craig, D., et al. Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization. Atherosclerosis 232 (2014), 191–196.
87. Peterson, M.B., Mead, R.J., Welty, J.D., Free amino acids in congestive heart failure. J Mol Cell Cardiol 5 (1973), 139–147.
88. Venturini, A., Ascione, R., Lin, H., et al. The importance of myocardial amino acids during ischemia and reperfusion in dilated left ventricle of patients with degenerative mitral valve disease. Mol Cell Biochem 330 (2009), 63–70.
89. Lai, L., Leone, T.C., Keller, M.P., et al. Energy metabolic reprogramming in the hypertrophied and early stage failing heart: a multisystems approach. Circ Heart Fail 7 (2014), 1022–1031.
90. Sansbury, B.E., DeMartino, A.M., Xie, Z., et al. Metabolomic analysis of pressure-overloaded and infarcted mouse hearts. Circ Heart Fail 7 (2014), 634–642.
91. Neishabouri, S.H., Hutson, S.M., Davoodi, J., Chronic activation of mTOR complex 1 by branched chain amino acids and organ hypertrophy. Amino Acids 47 (2015), 1167–1182.
92. Davoodi, J., Hutson, S., Constitutive activation of mTOR pathway by leucine causes heart hypertrophy which can be blocked by rapamycin. FASEB J 26:1 Suppl (2012), 1013–1016.
93. Djousse, L., Benkeser, D., Arnold, A., et al. Plasma free fatty acids and risk of heart failure: the Cardiovascular Health Study. Circ Heart Fail 6 (2013), 964–969.
94. Barouch, L.A., Berkowitz, D.E., Harrison, R.W., O'Donnell, C.P., Hare, J.M., Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice. Circulation 108 (2003), 754–759.
95. Christoffersen, C., Bollano, E., Lindegaard, M.L., et al. Cardiac lipid accumulation associated with diastolic dysfunction in obese mice. Endocrinology 144 (2003), 3483–3490.
96. Hamdani, N., Hervent, A.S., Vandekerckhove, L., et al. Left ventricular diastolic dysfunction and myocardial stiffness in diabetic mice is attenuated by inhibition of dipeptidyl peptidase 4. Cardiovasc Res 104 (2014), 423–431.
97. Venardos, K., De Jong, K.A., Elkamie, M., Connor, T., McGee, S.L., The PKD inhibitor CID755673 enhances cardiac function in diabetic db/db mice. PLoS One, 10, 2015, e0120934.
98. Li, R.J., Yang, J., Yang, Y., et al. Speckle tracking echocardiography in the diagnosis of early left ventricular systolic dysfunction in type II diabetic mice. BMC Cardiovasc Disord, 14, 2014, 141.
99. Semeniuk, L.M., Kryski, A.J., Severson, D.L., Echocardiographic assessment of cardiac function in diabetic db/db and transgenic db/db-hGLUT4 mice. Am J Physiol Heart Circ Physiol 283 (2002), H976–H982.
100. Chiu, H.C., Kovacs, A., Blanton, R.M., et al. Transgenic expression of fatty acid transport protein 1 in the heart causes lipotoxic cardiomyopathy. Circ Res 96 (2005), 225–233.
101. Lewandowski, E.D., Fischer, S.K., Fasano, M., et al. Acute L-CPT1 overexpression recapitulates reduced palmitate oxidation of cardiac hypertrophy. Circ Res 112 (2013), 57–65.
102. Karamanlidis, G., Garcia-Menendez, L., Kolwicz, S.C., Lee, C.F., Tian, R., Promoting PGC-1α-driven mitochondrial biogenesis is detrimental in pressure-overloaded mouse hearts. Am J Physiol Heart Circ Physiol 307 (2014), H1307–H1316.
103. Son, N.H., Park, T.S., Yamashita, H., et al. Cardiomyocyte expression of PPARgamma leads to cardiac dysfunction in mice. J Clin Invest 117 (2007), 2791–2801.
104. He, L., Kim, T., Long, Q., et al. Carnitine palmitoyltransferase-1b (CPT1b) deficiency aggravates pressure-overload-induced cardiac hypertrophy due to lipotoxicity. Circulation 126 (2012), 1705–1716.
105. Tenenbaum, A., Fisman, E.Z., Impaired glucose metabolism in patients with heart failure: pathophysiology and possible treatment strategies. Am J Cardiovasc Drugs 4 (2004), 269–280.
106. Shaye, K., Amir, T., Shlomo, S., Yechezkel, S., Fasting glucose levels within the high normal range predict cardiovascular outcome. Am Heart J 164 (2012), 111–116.
107. Thakker, G.D., Frangogiannis, N.G., Zymek, P.T., et al. Increased myocardial susceptibility to repetitive ischemia with high-fat diet-induced obesitity. Obesity 16 (2008), 2593–2600.
108. Holzem, K.M., Marmerstein, J.T., Madden, E.J., Efimov, I.R., Diet-induced obesity promotes altered remodeling and exacerbated cardiac hypertrophy following pressure overload. Physiol Rep, 3, 2015, e12489.
109. Christe, M.E., Rodgers, R.L., Cardiac glucose and fatty acid oxidation in the streptozotocin-induced diabetic spontaneously hypertensive rat. Hypertension 25 (1995), 235–241.
110. Sankaralingam, S., Abo Alrob, O., Zhang, L., et al. Lowering body weight in obese mice with diastolic heart failure improves cardiac insulin sensitivity and function: implications for the obesity paradox. Diabetes 64 (2015), 1643–1657.
111. Lopaschuk, G.D., Folmes, C.D., Stanley, W.C., Cardiac energy metabolism in obesity. Circ Res 101 (2007), 335–347.
112. Mori, J., Patel, V.B., Abo Alrob, O., et al. Angiotensin 1-7 ameliorates diabetic cardiomyopathy and diastolic dysfunction in db/db mice by reducing lipotoxicity and inflammation. Circ Heart Fail 7 (2014), 327–339.
113. Abel, E.D., Kaulbach, H.C., Tian, R., et al. Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart. J Clin Invest 104 (1999), 1703–1714.
114. Sun, W., Quan, N., Wang, L., et al. Cardiac-specific deletion of the pdha1 gene sensitizes heart to toxicological actions of ischemic stress. Toxicol Sci 151 (2016), 193–203.
115. Zordoky, B.N., Sung, M.M., Ezekowitz, J., et al. Metabolomic fingerprint of heart failure with preserved ejection fraction. PLoS One, 10, 2015, e0124844.
116. Lopaschuk, G.D., Metabolic modulators in heart disease: past, present, and future. Can J Cardiol 33 (2017), 838–849.