Glucose metabolism and cardiac hypertrophy

Cardiovascular Research

Volumn 90, Issue 2, 2011, Pages 194-201

  Kolwicz, Stephen C ^a   Tian, Rong ^a  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

Foetal metabolic profile; Glycolysis; Metabolic flexibility

Indexed keywords

FATTY ACID; GLUCOSE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; PENTOSE PHOSPHATE;

AEROBIC METABOLISM; ENZYME ACTIVATION; FATTY ACID OXIDATION; GENE EXPRESSION; GLUCOSE METABOLISM; GLUCOSE TRANSPORT; GLYCOLYSIS; HEART FAILURE; HEART HYPERTROPHY; METABOLIC REGULATION; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PRIORITY JOURNAL; REVIEW;

ANIMALS; BLOOD GLUCOSE; CARDIOMEGALY; GLYCOLYSIS; HUMANS; MYOCARDIUM; PENTOSE PHOSPHATE PATHWAY;

EID: 79955365919     PISSN: 00086363     EISSN: 17553245     Source Type: Journal    
DOI: 10.1093/cvr/cvr071     Document Type: Review

References (115)

1. Kresge N, Simoni RD, Hill RL Otto Fritz Meyerhof and the elucidation of the glycolytic pathway. J Biol Chem 2005;280:e3.
2. Kornberg H. Krebs and his trinity ofcycles. Nat Rev Mol Cell Biol 2000;1:225-228.
3. Mitchell P. Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 1961;191:144-148.
4. Hasin Y, Barry WH. Myocardial metabolic inhibition and membrane potential, con-traction, and potassium uptake. Am J Physiol 1984;247:H322-H329. (Pubitemid 14069025)
5. Nakamura K, Kusuoka H, Ambrosio G, Becker LC. Glycolysis is necessary to pre-serve myocardial Ca2+ homeostasis during beta-adrenergic stimulation. Am J Physiol 1993;264:H670-H678. (Pubitemid 23109854)
6. Lopaschuk GD, Belke DD, Gamble J, Itoi T, Schonekess BO. Regulation of fatty acid oxidation in the mammalian heart in health and disease. Biochim Biophys Acta 1994; 1213:263-276. (Pubitemid 24262910)
7. Fisher DJ. Oxygenation and metabolism in the developing heart. Semin Perinatol 1984;8:217-225.
8. Lopaschuk GD, Spafford MA, Marsh DR. Glycolysis is predominant source of myo-cardial ATP production immediately after birth. Am J Physiol 1991;261: H1698-H1705.
9. Barger PM, Kelly DP. Fatty acid utilization in the hypertrophied and failing heart: mol-ecular regulatory mechanisms. Am J Med Sci 1999;318:36-42. (Pubitemid 30387273)
10. Doenst T, Pytel G, Schrepper A, Amorim P, Farber G, Shingu Y et al. Decreased rates of substrate oxidation ex vivo predict the onset of heart failure and contractile dysfunction in rats with pressure overload. Cardiovasc Res 2010;86:461-470.
11. Razeghi P, Young ME, Alcorn JL, Moravec CS, Frazier OH, Taegtmeyer H. Metabolic gene expression in fetal and failing human heart Circulation 2001;104:2923-2931. (Pubitemid 33139104)
12. Saupe KW, Spindler M, Tian R, Ingwall JS. Impaired cardiac energetics in mice lacking muscle-specific isoenzymes ofcreatine kinase. Circ Res 1998;82:898-907. (Pubitemid 28234581)
13. Allard MF, Schonekess BO, Henning SL, English DR, Lopaschuk GD. Contribution of oxidative metabolism and glycolysis to ATP production in hypertrophied hearts. Am J Physiol 1994;267:H742-H750. (Pubitemid 24272494)
14. El Alaoui-Talibi Z, Guendouz A, Moravec M, Moravec J. Control of oxidative metab-olism in volume-overloaded rat hearts: effect of propionyl-L-carnitine. Am J Physiol 1997;272:H1615-H1624.
15. Leong HS, Grist M, Parsons H, Wambolt RB, Lopaschuk GD, Brownsey R et al. Accelerated rates ofglycolysis in the hypertrophied heart: are they a methodological artifact? Am J Physiol Endocrinol Metab 2002;282:E1039-E1045. (Pubitemid 34654717)
16. Nascimben L, Ingwall JS, Lorell BH, Pinz I, Schultz V, Tornheim K et al. Mechanisms for increased glycolysis in the hypertrophied rat heart. Hypertension 2004;44: 662-667. (Pubitemid 39435236)
17. Kagaya Y, Kanno Y, Takeyama D, Ishide N, Maruyama Y, Takahashi T et al. Effects of long-term pressure overload on regional myocardial glucose and free fatty acid uptake in rats. A quantitative autoradiographic study. Circulation 1990;81:1353-1361. (Pubitemid 20119634)
18. Tian R, Musi N, D'Agostino J, Hirshman MF, Goodyear LJ. Increased adenosine monophosphate-activated protein kinase activity in rat hearts with pressure-overload hypertrophy. Circulation 2001;104:1664-1669. (Pubitemid 32947531)
19. Zhang J, Duncker DJ, Ya X, Zhang Y, Pavek T, Wei H et al. Effect of left ventricular hypertrophy secondary to chronic pressure overload on transmural myocardial 2-deoxyglucose uptake. A 31P NMR spectroscopic study. Circulation 1995;92: 1274-1283.
20. Allard MF, Wambolt RB, Longnus SL, Grist M, Lydell CP, Parsons HL et al. Hyper-trophied rat hearts are less responsive to the metabolic and functional effects of insulin. Am J Physiol Endocrinol Metab 2000;279:E487-E493.
21. Scholz TD, Koppenhafer SL Reducing equivalent shuttles in developing porcine myocardium: enhanced capacity in the newborn heart. Pediatr Res 1995;38:221-227.
22. Scholz TD, Koppenhafer SL, TenEyck CJ, Schutte BC. Developmental regulation of the alpha-glycerophosphate shuttle in porcine myocardium. J Mol Cell Cardiol 1997; 29:1605-1613. (Pubitemid 27270231)
23. Scholz TD, Koppenhafer SL, tenEyck CJ, Schutte BC. Ontogeny of malate-aspartate shuttle capacity and gene expression in cardiac mitochondria. Am J Physiol 1998;274: C780-C788.
24. Griffin JL, O'Donnell JM, White LT, Hajjar RJ, Lewandowski ED. Postnatal expression and activity ofthe mitochondrial 2-oxoglutarate-malate carrier in intact hearts. Am J Physiol Cell Physiol 2000;279:C1704-C1709.
25. Rupert BE, Segar JL, Schutte BC, Scholz TD. Metabolic adaptation ofthe hypertro-phied heart: role ofthe malate/aspartate and alpha-glycerophosphate shuttles. J Mol Cell Cardiol 2000;32:2287-2297. (Pubitemid 32039779)
26. Lewandowski ED, O'Donnell JM, Scholz TD, Sorokina N, Buttrick PM. Recruitment of NADH shuttling in pressure-overloaded and hypertrophic rat hearts. Am J Physiol Cell Physiol 2007;292:C1880-C1886. (Pubitemid 47080576)
27. Allard MF, Henning SL, Wambolt RB, Granleese SR, English DR, Lopaschuk GD. Gly-cogen metabolism in the aerobic hypertrophied rat heart. Circulation 1997;96: 676-682. (Pubitemid 27329450)
28. Wambolt RB, Henning SL, English DR, Dyachkova Y, Lopaschuk GD, Allard MF. Glucose utilization and glycogen turnover are accelerated in hypertrophied rat hearts during severe low-flow ischemia. J Mol Cell Cardiol 1999;31:493-502. (Pubitemid 29121636)
29. Wambolt RB, Lopaschuk GD, Brownsey RW, Allard MF. Dichloroacetate improves postischemic function of hypertrophied rat hearts. J Am Coll Cardiol 2000;36: 1378-1385.
30. Taegtmeyer H, Overturf ML. Effects of moderate hypertension on cardiac function and metabolism in the rabbit. Hypertension 1988;11:416-426.
31. Smith SH, Kramer MF, Reis I, Bishop SP, Ingwall JS. Regional changes in creatine kinase and myocyte size in hypertensive and nonhypertensive cardiac hypertrophy Circ Res 1990;67:1334-1344.
32. Akki A, Smith K, Seymour AM. Compensated cardiac hypertrophy is characterised by a decline in palmitate oxidation. Mol Cell Biochem 2008;311:215-224.
33. Schonekess BO, Allard MF, Lopaschuk GD. Propionyl L-carnitine improvement of hypertrophied heart function is accompanied by an increase in carbohydrate oxi-dation. Circ Res 1995;77:726-734.
34. Young ME, Laws FA, Goodwin GW, Taegtmeyer H. Reactivation of peroxisome proliferator-activated receptor alpha is associated with contractile dysfunction in hypertrophied rat heart. J Biol Chem 2001;276:44390-44395.
35. Owen OE, Kalhan SC, Hanson RW. The key role of anaplerosis and cataplerosis for citric acid cycle function. J Biol Chem 2002;277:30409-30412. (Pubitemid 34970728)
36. Pound KM, Sorokina N, Ballal K, Berkich DA, Fasano M, Lanoue KF et al. Substrate-enzyme competition attenuates upregulated anaplerotic flux through malic enzyme in hypertrophied rat heart and restores triacylglyceride content: attenuating upregulated anaplerosis in hypertrophy. Circ Res 2009;104:805-812.
37. Sorokina N, O'Donnell JM, McKinney RD, Pound KM, Woldegiorgis G, LaNoue KF et al. Recruitment of compensatory pathways to sustain oxidative flux with reduced carnitine palmitoyltransferase I activity characterizes inefficiency in energy metab-olism in hypertrophied hearts. Circulation 2007;115:2033-2041. (Pubitemid 46625954)
38. Tian R. Transcriptional regulation of energy substrate metabolism in normal and hypertrophied heart. Curr Hypertens Rep 2003;5:454-458. (Pubitemid 38898969)
39. Arany Z, Novikov M, Chin S, Ma Y, Rosenzweig A, Spiegelman BM. Transverse aortic constriction leads to accelerated heart failure in mice lacking PPAR-gamma coactiva-tor 1alpha. Proc Natl Acad Sci USA 2006;103:10086-10091. (Pubitemid 43993627)
40. Lehman JJ, Kelly DP. Transcriptional activation of energy metabolic switches in the developing and hypertrophied heart. Clin Exp Pharmacol Physiol 2002;29:339-345. (Pubitemid 34227071)
41. Barger PM, Brandt JM, Leone TC, Weinheimer CJ, Kelly DP. Deactivation of peroxi-some proliferator-activated receptor-alpha during cardiac hypertrophic growth. J Clin Invest 2000;105:1723-1730. (Pubitemid 30421753)
42. Sack MN, Disch DL, Rockman HA, Kelly DP. A role for Sp and nuclear receptor transcription factors in a cardiac hypertrophic growth program. Proc Natl Acad Sci USA 1997;94:6438-6443. (Pubitemid 27270703)
43. Depre C, Shipley GL, Chen W, Han Q, Doenst T, Moore ML et al. Unloaded heart in vivo replicates fetal gene expression of cardiac hypertrophy. Nat Med 1998;4: 1269-1275. (Pubitemid 28512107)
44. Aitman TJ, Glazier AM, Wallace CA, Cooper LD, Norsworthy PJ, Wahid FN et al. Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. Nat Genet 1999;21:76-83. (Pubitemid 29036288)
45. Vork MM, Trigault N, Snoeckx LH, Glatz JF, van der Vusse GJ. Heterogeneous dis-tribution of fatty acid-binding protein in the hearts of Wistar Kyoto and spon-taneously hypertensive rats. J Mol Cell Cardiol 1992;24:317-321.
46. Christian B, El Alaoui-Talibi Z, Moravec M, Moravec J. Palmitate oxidation by the mitochondria from volume-overloaded rat hearts. Mol Cell Biochem 1998;180: 117-128. (Pubitemid 28118811)
47. el Alaoui-Talibi Z, Landormy S, Loireau A, Moravec J. Fatty acid oxidation and mech-anical performance of volume-overloaded rat hearts. Am J Physiol 1992;262: H1068-H1074.
48. Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O et al. Transcriptional coacti-vator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab 2005;1:259-271. (Pubitemid 43960608)
49. Lai L, Leone TC, Zechner C, Schaeffer PJ, Kelly SM, Flanagan DP et al. Transcrip-tional coactivators PGC-1alpha and PGC-lbeta control overlapping programs required for perinatal maturation ofthe heart. Genes Dev 2008;22:1948-1961. (Pubitemid 352008642)
50. Paternostro G, Clarke K, Heath J, Seymour AM, Radda GK Decreased GLUT-4 mRNA content and insulin-sensitive deoxyglucose uptake show insulin resistance in the hypertensive rat heart. Cardiovasc Res 1995;30:205-211.
51. Allard MF, Parsons HL, Saeedi R, Wambolt RB, Brownsey R. AMPK and metabolic adaptation by the heart to pressure overload. Am J Physiol Heart Circ Physiol 2007; 292:H140-H148. (Pubitemid 46115922)
52. Depre C, Rider MH, Veitch K, Hue L. Role of fructose 2, 6-bisphosphate in the control of heart glycolysis. J Biol Chem 1993;268:13274-13279. (Pubitemid 23307748)
53. Marsin AS, Bertrand L, Rider MH, Deprez J, Beauloye C, Vincent MF et al. Phos-phorylation and activation of heart PFK-2 by AMPK has a role in the stimulation ofglycolysis during ischaemia. Curr Biol 2000;10:1247-1255.
54. Karamanlidis G, Nascimben L, Couper GS, Shekar PS, del Monte F, Tian R. Defective DNA replication impairs mitochondrial biogenesis in human failing hearts. Circ Res 2010;106:1541-1548.
55. Sihag S, Cresci S, Li AY, Sucharov CC, Lehman JJ. PGC-1alpha and ERRalpha target gene downregulation is a signature ofthe failing human heart. J Mol Cell Cardiol 2009; 46:201-212.
56. Neubauer S. The failing heart\an engine out of fuel. N Engl J Med 2007;356: 1140-1151. (Pubitemid 46425598)
57. Iozzo P. Metabolic toxicity ofthe heart: insights from molecular imaging. Nutr Metab Cardiovasc Dis 2010;20:147-156.
58. Rijzewijk LJ, van der Meer RW, Lamb HJ, de Jong HW, Lubberink M, Romijn JA et al. Altered myocardial substrate metabolism and decreased diastolic function in nonis-chemic human diabetic cardiomyopathy: studies with cardiac positron emission tom-ography and magnetic resonance imaging. J Am Coll Cardiol 2009;54:1524-1532.
59. Tuunanen H, Engblom E, Naum A, Nagren K, Scheinin M, Hesse B et al. Trimetazi-dine, a metabolic modulator, has cardiac and extracardiac benefits in idiopathic dilated cardiomyopathy. Circulation 2008;118:1250-1258.
60. Taylor M, Wallhaus TR, Degrado TR, Russell DC, Stanko P, Nickles RJ 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 2001;42:55-62. (Pubitemid 32104778)
61. Wallhaus TR, Taylor M, DeGrado TR, Russell DC, Stanko P, Nickles RJ et al. Myocardial free fatty acid and glucose use after carvedilol treatment in patients with congestive heart failure. Circulation 2001;103:2441-2446. (Pubitemid 32493369)
62. Horecker BL, Mehler AH. Carbohydrate metabolism. Annu Rev Biochem 1955;24: 207-274.
63. Doiron B, Cuif MH, Chen R, Kahn A. Transcriptional glucose signaling through the glucose response element is mediated by the pentose phosphate pathway. J Biol Chem 1996;271:5321-5324. (Pubitemid 26083863)
64. Nishimura M, Uyeda K. Purification and characterization of a novel xylulose 5-phosphate-activated protein phosphatase catalyzing dephosphorylation of fructose-6-phosphate, 2-kinase:fructose-2, 6-bisphosphatase. J Biol Chem 1995;270: 26341-26346.
65. Neely JR, Morgan HE. Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle. Annu Rev Physiol 1974;36:413-459.
66. Zimmer HG. Regulation of and intervention into the oxidative pentose phosphate pathway and adenine nucleotide metabolism in the heart. Mol Cell Biochem 1996; 160-161:101-109.
67. Meerson FZ, Spiritchev VB, Pshennikova MG, Djachkova LV. The role of the pentose-phosphate pathway in adjustment ofthe heart to a high load and the devel-opment of myocardial hypertrophy. Experientia 1967;23:530-532.
68. Zimmer HG, Ibel H, Steinkopff G. Studies on the hexose monophosphate shunt in the myocardium during development of hypertrophy. Adv Myocardiol 1980;1: 487-492.
69. Chess DJ, Khairallah RJ, O'Shea KM, Xu W, Stanley WC. A high-fat diet increases adiposity but maintains mitochondrial oxidative enzymes without affecting develop-ment of heart failure with pressure overload. Am J Physiol Heart Circ Physiol 2009;297: H1585-H1593.
70. Gupte SA, Levine RJ, Gupte RS, Young ME, Lionetti V, Labinskyy V et al. Glucose-6-phosphate dehydrogenase-derived NADPH fuels superoxide production in the failing heart. J Mol Cell Cardiol 2006;41:340-349. (Pubitemid 44080215)
71. Young ME, Yan J, Razeghi P, Cooksey RC, Guthrie PH, Stepkowski SM et al. Pro-posed regulation of gene expression by glucose in rodent heart. Gene Regul Syst Bio 2007;1:251-262.
72. Jain M, Cui L, Brenner DA, Wang B, Handy DE, Leopold JA et al. Increased myocar-dial dysfunction after ischemia-reperfusion in mice lacking glucose-6-phosphate dehydrogenase. Circulation 2004;109:898-903. (Pubitemid 38252743)
73. Rajasekaran NS, Connell P, Christians ES, Yan LJ, Taylor RP, Orosz A et al. Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Cell 2007;130:427-439. (Pubitemid 47208522)
74. Henning SL, Wambolt RB, Schonekess BO, Lopaschuk GD, Allard MF. Contribution of glycogen to aerobic myocardial glucose utilization. Circulation 1996;93: 1549-1555. (Pubitemid 26115420)
75. Goodwin GW, Taylor CS, Taegtmeyer H. Regulation of energy metabolism ofthe heart during acute increase in heart work. J Biol Chem 1998;273:29530-29539. (Pubitemid 28509960)
76. Neely JR, Whitfield CF, Morgan HE. Regulation ofglycogenolysis in hearts: effects of pressure development, glucose, and FFA. Am J Physiol 1970;219:1083-1088.
77. Schonekess BO, Allard MF, Henning SL, Wambolt RB, Lopaschuk GD. Contribution of glycogen and exogenous glucose to glucose metabolism during ischemia in the hypertrophied rat heart. Circ Res 1997;81:540-549. (Pubitemid 27432741)
78. Hebert LF Jr, Daniels MC, Zhou J, Crook ED, Turner RL, Simmons ST et al. Over-expression ofglutamine: fructose-6-phosphate amidotransferase in transgenic mice leads to insulin resistance. J Clin Invest 1996;98:930-936. (Pubitemid 26293310)
79. Wells L, Vosseller K, Hart GW. Glycosylation of nucleocytoplasmic proteins: signal transduction and O-GlcNAc. Science 2001;291:2376-2378. (Pubitemid 32231793)
80. Watson LJ, Facundo HT, Ngoh GA, Ameen M, Brainard RE, Lemma KM et al. O-linked beta-N-acetylglucosamine transferase is indispensable in the failing heart. Proc Natl Acad Sci USA 2010;107:17797-17802.
81. Clark RJ, McDonough PM, Swanson E, Trost SU, Suzuki M, Fukuda M et al. Diabetes and the accompanying hyperglycemia impairs cardiomyocyte calcium cycling through increased nuclear O-GlcNAcylation. J Biol Chem 2003;278:44230-44237. (Pubitemid 37377167)
82. Hu Y, Belke D, Suarez J, Swanson E, Clark R, Hoshijima M et al. Adenovirus-mediated overexpression of O-GlcNAcase improves contractile function in the dia-betic heart. Circ Res 2005;96:1006-1013. (Pubitemid 40712801)
83. Fiordaliso F, Leri A, Cesselli D, Limana F, Safai B, Nadal-Ginard B et al. Hyperglyce-mia activates p53 and p53-regulated genes leading to myocyte cell death. Diabetes 2001;50:2363-2375. (Pubitemid 33641924)
84. Wellen KE, Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB. ATP-citrate lyase links cellular metabolism to histone acetylation. Science 2009;324: 1076-1080.
85. Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang Tet al. Regulation ofcellular metabolism by protein lysine acetylation. Science 2010;327:1000-1004.
86. Samant SA, Courson DS, Sundaresan NR, Pillai VB, Tan M, Zhao Y et al. HDAC3-dependent reversible lysine acetylation of cardiac myosin heavy chain isoforms modulates their enzymatic and motor activity. J Biol Chem 2011;286:5567-5577.
87. Yang J, Moravec CS, Sussman MA, DiPaola NR, Fu D, Hawthorn L et al. Decreased SLIM1 expression and increased gelsolin expression in failing human hearts measured by high-density oligonucleotide arrays. Circulation 2000;102: 3046-3052.
88. Johnson BF, Nesto RW, Pfeifer MA, Slater WR, Vinik AI, Chyun DA et al. Cardiac abnormalities in diabetic patients with neuropathy: effects of aldose reductase inhibi-tor administration. Diabetes Care 2004;27:448-454. (Pubitemid 38174070)
89. Tang WH, Cheng WT, Kravtsov GM, Tong XY, Hou XY, Chung SK et al. Cardiac contractile dysfunction during acute hyperglycemia due to impairment of SERCA by polyol pathway-mediated oxidative stress. Am J Physiol Cell Physiol 2010;299: C643-C653.
90. Hwang YC, Kaneko M, Bakr S, Liao H, Lu Y, Lewis ER et al. Central role for aldose reductase pathway in myocardial ischemic injury. Faseb J 2004;18:1192-1199. (Pubitemid 39006881)
91. Liao R, Jain M, Cui L, D'Agostino J, Aiello F, Luptak I et al. Cardiac-specific overex-pression of GLUT1 prevents the development of heart failure attributable to pressure overload in mice. Circulation 2002;106:2125-2131. (Pubitemid 35192820)
92. Luptak I, Balschi JA, Xing Y, Leone TC, Kelly DP, Tian R. Decreased contractile and metabolic reserve in peroxisome proliferator-activated receptor-alpha-null hearts can be rescued by increasing glucose transport and utilization. Circulation 2005; 112:2339-2346. (Pubitemid 41464577)
93. Luptak I, Yan J, Cui L, Jain M, Liao R, Tian R. Long-term effects of increased glucose entry on mouse hearts during normal aging and ischemic stress. Circulation 2007;116: 901-909. (Pubitemid 47300914)
94. Yan J, Young ME, Cui L, Lopaschuk GD, Liao R, Tian R. Increased glucose uptake and oxidation in mouse hearts prevent high fatty acid oxidation but cause cardiac dys-function in diet-induced obesity. Circulation 2009;119:2818-2828.
95. Hu P, Zhang D, Swenson L, Chakrabarti G, Abel ED, Litwin SE. Minimally invasive aortic banding in mice: effects of altered cardiomyocyte insulin signaling during pressure overload. Am J Physiol Heart Circ Physiol 2003;285:H1261-H1269. (Pubitemid 37048185)
96. Domenighetti AA, Danes VR, Curl CL, Favaloro JM, Proietto J, Delbridge LM. Tar-geted GLUT-4 deficiency in the heart induces cardiomyocyte hypertrophy and impaired contractility linked with Ca(2+) and proton flux dysregulation. J Mol Cell Cardiol 2010;48:663-672.
97. Bhashyam S, Fields AV, Patterson B, Testani JM, Chen L, Shen YT et al. Glucagon-like peptide-1 increases myocardial glucose uptake via p38alpha MAP kinase-mediated, nitric oxide-dependent mechanisms in conscious dogs with dilated cardiomyopathy. Circ Heart Fail 2010;3:512-521.
98. D'Alessio DA, Kahn SE, Leusner CR, Ensinck JW. Glucagon-like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin-independent glucose disposal. J Clin Invest 1994;93:2263-2266. (Pubitemid 24143111)
99. Nikolaidis LA, Mankad S, Sokos GG, Miske G, Shah A, Elahi D et al. Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation 2004;109: 962-965. (Pubitemid 38282847)
100. Poornima I, Brown SB, Bhashyam S, Parikh P, Bolukoglu H, Shannon RP. Chronic glucagon-like peptide-1 infusion sustains left ventricular systolic function and pro-longs survival in the spontaneously hypertensive, heart failure-prone rat. Circ Heart Fail 2008;1:153-160.
101. Lionetti V, Linke A, Chandler MP, Young ME, Penn MS, Gupte S et al. Carnitine pal-mitoyl transferase-I inhibition prevents ventricular remodeling and delays decom-pensation in pacing-induced heart failure. Cardiovasc Res 2005;66:454-461. (Pubitemid 40725757)
102. Turcani M, Rupp H. Etomoxir improves left ventricular performance of pressure-overloaded rat heart. Circulation 1997;96:3681-3686. (Pubitemid 27513449)
103. Rupp H, Vetter R. Sarcoplasmic reticulum function and carnitine palmitoyltransferase-1 inhibition during progression of heart failure. Br J Pharmacol 2000;131:1748-1756. (Pubitemid 32056442)
104. Vitale C, Wajngaten M, Sposato B, Gebara O, Rossini P, Fini M et al. Trimetazidine improves left ventricular function and quality of life in elderly patients with coronary artery disease. Eur Heart J 2004;25:1814-1821. (Pubitemid 39330232)
105. Tuunanen H, Engblom E, Naum A, Nagren K, Hesse B, Airaksinen KE et al. Free fatty acid depletion acutely decreases cardiac work and efficiency in cardiomyopathic heart failure. Circulation 2006;114:2130-2137. (Pubitemid 44747893)
106. Finck BN, Lehman JJ, Leone TC, Welch MJ, Bennett MJ, Kovacs A et al. The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest 2002;109:121-130. (Pubitemid 34052548)
107. Morgan EE, Rennison JH, Young ME, McElfresh TA, Kung TA, Tserng KY et al. Effects of chronic activation of peroxisome proliferator-activated receptor-alpha or high-fat feeding in a rat infarct model of heart failure. Am J Physiol Heart Circ Physiol 2006;290: H1899-H1904.
108. Labinskyy V, Bellomo M, Chandler MP, Young ME, Lionetti V, Qanud Ket al. Chronic activation of peroxisome proliferator-activated receptor-alpha with fenofibrate pre-vents alterations in cardiac metabolic phenotype without changing the onset of decompensation in pacing-induced heart failure. J Pharmacol Exp Ther 2007;321: 165-171. (Pubitemid 46456959)
109. Okere IC, Young ME, McElfresh TA, Chess DJ, Sharov VG, Sabbah HN et al. Low carbohydrate/high-fat diet attenuates cardiac hypertrophy, remodeling, and altered gene expression in hypertension. Hypertension 2006;48:1116-1123. (Pubitemid 44772716)
110. Rennison JH, McElfresh TA, Okere IC, Vazquez EJ, Patel HV, Foster AB et al. High-fat diet postinfarction enhances mitochondrial function and does not exacerbate left ventricular dysfunction. Am J Physiol Heart Circ Physiol 2007;292: H1498-H1506. (Pubitemid 46377138)
111. Kalantar-Zadeh K, Block G, Horwich T, Fonarow GC. Reverse epidemiology of con-ventional cardiovascular risk factors in patients with chronic heart failure. J Am Coll Cardiol 2004;43:1439-1444. (Pubitemid 38496352)
112. Oreopoulos A, Padwal R, Kalantar-Zadeh K, Fonarow GC, Norris CM, McAlister FA. Body mass index and mortality in heart failure: a meta-analysis. Am Heart J 2008;156:13-22. (Pubitemid 351862293)
113. Wende A, Pires K, Wayment B, Tuinei J, Jeoung N, Litwin S et al. Pyruvate dehydro-genase kinase 4 (PDK4) deficiency does not impair the cardiac metabolic or contrac-tile response to pressure overload hypertrophy. Circulation 2009;120:S880.
114. Kolwicz S, Olson D, Ngoy S, Liao R, Tian R. Cardiac-specific deletion of acetyl-coA carboxylase 2 (ACC2) maintains fatty acid oxidation and left ventricular function during pressure-overload hypertrophy. Circulation 2009;120:S855.
115. Zhao G, Jeoung NH, Burgess SC, Rosaaen-Stowe KA, Inagaki T, Latif S et al. Over-expression of pyruvate dehydrogenase kinase 4 in heart perturbs metabolism and exacerbates calcineurin-induced cardiomyopathy. Am J Physiol Heart Circ Physiol 2008;294:H936-H943. (Pubitemid 351253306)