Shedding light on the enigma of myocardial lipotoxicity: The involvement of known and putative regulators of fatty acid storage and mobilization

American Journal of Physiology - Endocrinology and Metabolism

Volumn 298, Issue 5, 2010, Pages

  Brindley, David N ^a   Kok, Bernard P C ^a   Kienesberger, Petra C ^a   Lehner, Richard ^a   Dyck, Jason R B ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

Author keywords

Apoptosis; Ceramides; Energy partitioning; Fatty acid oxidation; Insulin resistance

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; CERAMIDE; DIACYLGLYCEROL; DIACYLGLYCEROL ACYLTRANSFERASE; ETOMOXIR; FATTY ACID; FIBRIC ACID DERIVATIVE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; OXFENICINE; PHOSPHATIDIC ACID; RANOLAZINE; TRIACYLGLYCEROL; TRIMETAZIDINE;

CARDIOTOXICITY; DIABETES MELLITUS; ENERGY METABOLISM; ESTERIFICATION; FATTY ACID TRANSPORT; HEART DISEASE; HEART MUSCLE CELL; HUMAN; INSULIN RESISTANCE; LIPID METABOLISM; LIPID STORAGE; LIPOGENESIS; MYOCARDIAL LIPOTOXICITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; APOPTOSIS; ENERGY METABOLISM; FATTY ACIDS; HUMANS; INSULIN RESISTANCE; MYOCYTES, CARDIAC; PROTEIN TRANSPORT;

EID: 77950788493     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00509.2009     Document Type: Review

References (179)

1. Aasum E, Cooper M, Severson DL, Larsen TS. Effect of BM 17.0744, a PPARalpha ligand, on the metabolism of perfused hearts from control and diabetic mice. Can J Physiol Pharmacol 83: 183-190, 2005. (Pubitemid 40695392)
2. Aasum E, Khalid AM, Gudbrandsen OA, How OJ, Berge RK, Larsen TS. Fenofibrate modulates cardiac and hepatic metabolism and increases ischemic tolerance in diet-induced obese mice. J Mol Cell Cardiol 44: 201-209, 2008.
3. Abel ED, Litwin SE, Sweeney G. Cardiac remodeling in obesity. Physiol Rev 88: 389-419, 2008.
4. Abourbih S, Filion KB, Joseph L, Schiffrin EL, Rinfret S, Poirier P, Pilote L, Genest J, Eisenberg MJ. Effect of fibrates on lipid profiles and cardiovascular outcomes: a systematic review. Am J Med 122: 962 e961-968, 2009.
5. Baranowski M, Blachnio A, Zabielski P, Gorski J. PPARalpha agonist induces the accumulation of ceramide in the heart of rats fed high-fat diet. J Physiol Pharmacol 58: 57-72, 2007. (Pubitemid 350021137)
6. Barger PM, Kelly DP. PPAR signaling in the control of cardiac energy metabolism. Trends Cardiovasc Med 10: 238-245, 2000. (Pubitemid 32229879)
7. Bartels ED, Nielsen JM, Hellgren LI, Ploug T, Nielsen LB. Cardiac expression of microsomal triglyceride transfer protein is increased in obesity and serves to attenuate cardiac triglyceride accumulation. PLoS One 4: e5300, 2009.
8. Barter PJ, Rye KA. Cardioprotective properties of fibrates: which fibrate, which patients, what mechanism? Circulation 113: 1553-1555, 2006.
9. Bays H, Mandarino L, DeFronzo RA. Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. J Clin Endocrinol Metab 89: 463-478, 2004. (Pubitemid 38269844)
10. Bielawska AE, Shapiro JP, Jiang L, Melkonyan HS, Piot C, Wolfe CL, Tomei LD, Hannun YA, Umansky SR. Ceramide is involved in triggering of cardiomyocyte apoptosis induced by ischemia and reperfusion. Am J Pathol 151: 1257-1263, 1997. (Pubitemid 27479755)
11. Bonen A, Holloway GP, Tandon NN, Han XX, McFarlan J, Glatz JF, Luiken JJ. Cardiac and skeletal muscle fatty acid transport and transporters and triacylglycerol and fatty acid oxidation in lean and Zucker diabetic fatty rats. Am J Physiol Regul Integr Comp Physiol 297: R1202-R1212, 2009.
12. Boudina S, Abel ED. Mitochondrial uncoupling: a key contributor to reduced cardiac efficiency in diabetes. Physiology (Bethesda) 21: 250-258, 2006.
13. Boudina S, Sena S, O'Neill BT, Tathireddy P, Young ME, Abel ED. Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity. Circulation 112: 2686-2695, 2005.
14. Boudina S, Sena S, Theobald H, Sheng X, Wright JJ, Hu XX, Aziz S, Johnson JI, Bugger H, Zaha VG, Abel ED. Mitochondrial energetics in the heart in obesity-related diabetes: direct evidence for increased uncoupled respiration and activation of uncoupling proteins. Diabetes 56: 2457-2466, 2007.
15. Brindley DN. Neuroendocrine regulation and obesity. Int J Obesity 16: S75-S79, 1992.
16. Brookheart RT, Michel CI, Schaffer JE. As a matter of fat. Cell Metab 10: 9-12, 2009.
17. Buchanan J, Mazumder PK, Hu P, Chakrabarti G, Roberts MW, Yun UJ, Cooksey RC, Litwin SE, Abel ED. Reduced cardiac efficiency and altered substrate metabolism precedes the onset of hyperglycemia and contractile dysfunction in two mouse models of insulin resistance and obesity. Endocrinology 146: 5341-5349, 2005.
18. Burgdorf C, Hansel L, Heidbreder M, Johren O, Schutte F, Schunkert H, Kurz T. Suppression of cardiac phosphatidate phosphohydrolase 1 activity and lipin mRNA expression in Zucker diabetic fatty rats and humans with type 2 diabetes mellitus. Biochem Biophys Res Commun 390: 165-170, 2009.
19. Campbell FM, Kozak R, Wagner A, Altarejos JY, Dyck JR, Belke DD, Severson DL, Kelly DP, Lopaschuk GD. A role for peroxisome proliferator-activated receptor alpha (PPARalpha) in the control of cardiac malonyl-CoA levels: reduced fatty acid oxidation rates and increased glucose oxidation rates in the hearts of mice lacking PPARalpha are associated with higher concentrations of malonyl-CoA and reduced expression of malonyl-CoA decarboxylase. J Biol Chem 277: 4098-4103, 2002.
20. Cao J, Li JL, Li D, Tobin JF, Gimeno RE. Molecular identification of microsomal acyl-CoA:glycerol-3-phosphate acyltransferase, a key enzyme in de novo triacylglycerol synthesis. Proc Natl Acad Sci USA 103: 19695-19700, 2006.
21. Carley AN, Semeniuk LM, Shimoni Y, Aasum E, Larsen TS, Berger JP, Severson DL. Treatment of type 2 diabetic db/db mice with a novel PPARγ agonist improves cardiac metabolism but not contractile function. Am J Physiol Endocrinol Metab 286: E449-E455, 2004.
22. Carley AN, Severson DL. Fatty acid metabolism is enhanced in type 2 diabetic hearts. Biochim Biophys Acta 1734: 112-126, 2005.
23. Cascales C, Mangiapane EH, Brindley DN. Oleic acid promotes the activation and translocation of phosphatidate phosphohydrolase from the cytosol to particulate fractions of isolated rat hepatocytes. Biochem J 219: 911-916, 1984.
24. Chandler MP, Chavez PN, McElfresh TA, Huang H, Harmon CS, Stanley WC. Partial inhibition of fatty acid oxidation increases regional contractile power and efficiency during demand-induced ischemia. Cardiovasc Res 59: 143-151, 2003.
25. Chavez JA, Knotts TA, Wang LP, Li G, Dobrowsky RT, Florant GL, Summers SA. A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids. J Biol Chem 278: 10297-10303, 2003.
26. Chavez JA, Summers SA. Characterizing the effects of saturated fatty acids on insulin signaling and ceramide and diacylglycerol accumulation in 3T3-L1 adipocytes and C2C12 myotubes. Arch Biochem Biophys 419: 101-109, 2003.
27. Cheng L, Ding G, Qin Q, Huang Y, Lewis W, He N, Evans RM, Schneider MD, Brako FA, Xiao Y, Chen YE, Yang Q. Cardiomyocyte-restricted peroxisome proliferator-activated receptor-delta deletion perturbs myocardial fatty acid oxidation and leads to cardiomyopathy. Nat Med 10: 1245-1250, 2004.
28. Chiu HC, Kovacs A, Blanton RM, Han X, Courtois M, Weinheimer CJ, Yamada KA, Brunet S, Xu H, Nerbonne JM, Welch MJ, Fettig NM, Sharp TL, Sambandam N, Olson KM, Ory DS, Schaffer JE. Transgenic expression of fatty acid transport protein 1 in the heart causes lipotoxic cardiomyopathy. Circ Res 96: 225-233, 2005.
29. Chiu HC, Kovacs A, Ford DA, Hsu FF, Garcia R, Herrero P, Saffitz JE, Schaffer JE. A novel mouse model of lipotoxic cardiomyopathy. J Clin Invest 107: 813-822, 2001.
30. Cianflone K, Xia Z, Chen LY. Critical review of acylation-stimulating protein physiology in humans and rodents. Biochim Biophys Acta 1609: 127-143, 2003.
31. Coll T, Eyre E, Rodriguez-Calvo R, Palomer X, Sanchez RM, Merlos M, Laguna JC, Vazquez-Carrera M. Oleate reverses palmitate-induced insulin resistance and inflammation in skeletal muscle cells. J Biol Chem 283: 11107-11116, 2008.
32. Cook WS, Yeldandi AV, Rao MS, Hashimoto T, Reddy JK. Less extrahepatic induction of fatty acid beta-oxidation enzymes by PPAR alpha. Biochem Biophys Res Commun 278: 250-257, 2000.
33. Coort SL, Hasselbaink DM, Koonen DP, Willems J, Coumans WA, Chabowski A, van der Vusse GJ, Bonen A, Glatz JF, Luiken JJ. Enhanced sarcolemmal FAT/CD36 content and triacylglycerol storage in cardiac myocytes from obese zucker rats. Diabetes 53: 1655-1663, 2004.
34. Coort SL, Luiken JJ, van der Vusse GJ, Bonen A, Glatz JF. Increased FAT (fatty acid translocase)/CD36-mediated long-chain fatty acid uptake in cardiac myocytes from obese Zucker rats. Biochem Soc Trans 32: 83-85, 2004.
35. Cuthbert KD, Dyck JR. Malonyl-CoA decarboxylase is a major regulator of myocardial fatty acid oxidation. Curr Hypertens Rep 7: 407-411, 2005.
36. de Vries JE, Vork MM, Roemen TH, de Jong YF, Cleutjens JP, van der Vusse GJ, van Bilsen M. Saturated but not mono-unsaturated fatty acids induce apoptotic cell death in neonatal rat ventricular myocytes. J Lipid Res 38: 1384-1394, 1997.
37. Depre C, Young ME, Ying J, Ahuja HS, Han Q, Garza N, Davies PJ, Taegtmeyer H. Streptozotocin-induced changes in cardiac gene expression in the absence of severe contractile dysfunction. J Mol Cell Cardiol 32: 985-996, 2000.
38. Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature 444: 881-887, 2006.
39. Dey D, Basu D, Roy SS, Bandyopadhyay A, Bhattacharya S. Involvement of novel PKC isoforms in FFA induced defects in insulin signaling. Mol Cell Endocrinol 246: 60-64, 2006.
40. Dolinsky VW, Sipione S, Lehner R, Vance DE. The cloning and expression of a murine triacylglycerol hydrolase cDNA and the structure of its corresponding gene. Biochim Biophys Acta 1532: 162-172, 2001.
41. Donkor J, Sariahmetoglu M, Dewald J, Brindley DN, Reue K. Three mammalian lipins act as phosphatidate phosphatases with distinct tissue expression patterns. J Biol Chem 282: 3450-3457, 2007.
42. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 115: 1343-1351, 2005.
43. Duez H, Lewis G. Type 2 Diabetes mellitus: an evidence-based approach to practical management In: Contemporary Endocrinology, edited by Feinglos M and Bethel M. Totowa, NJ: Humana, 2008, p. 49-73.
44. Duncan JG, Fong JL, Medeiros DM, Finck BN, Kelly DP. Insulin-resistant heart exhibits a mitochondrial biogenic response driven by the peroxisome proliferator-activated receptor-alpha/PGC-1alpha gene regulatory pathway. Circulation 115: 909-917, 2007.
45. Dyck JR, Cheng JF, Stanley WC, Barr R, Chandler MP, Brown S, Wallace D, Arrhenius T, Harmon C, Yang G, Nadzan AM, Lopaschuk GD. Malonyl coenzyme a decarboxylase inhibition protects the ischemic heart by inhibiting fatty acid oxidation and stimulating glucose oxidation. Circ Res 94: e78-e84, 2004.
46. Dyck JR, Lopaschuk GD. AMPK alterations in cardiac physiology and pathology: enemy or ally? J Physiol 574: 95-112, 2006.
47. Echtay KS, Roussel D, St-Pierre J, Jekabsons MB, Cadenas S, Stuart JA, Harper JA, Roebuck SJ, Morrison A, Pickering S, Clapham JC, Brand MD. Superoxide activates mitochondrial uncoupling proteins. Nature 415: 96-99, 2002.
48. El-Assaad W, Buteau J, Peyot ML, Nolan C, Roduit R, Hardy S, Joly E, Dbaibo G, Rosenberg L, Prentki M. Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death. Endocrinology 144: 4154-4163, 2003. (Pubitemid 37088771)
49. Faraj M, Sniderman AD, Cianflone K. ASP enhances in situ lipoprotein lipase activity by increasing fatty acid trapping in adipocytes. J Lipid Res 45: 657-666, 2004. (Pubitemid 38405672)
50. Fazio S. Management of mixed dyslipidemia in patients with or at risk for cardiovascular disease: a role for combination fibrate therapy. Clin Ther 30: 294-306, 2008. (Pubitemid 351479210)
51. Fein FS, Sonnenblick Diabetic cardiomyopathy EH. Cardiovasc Drugs Ther 8: 65-73, 1994.
52. Finck BN. The PPAR regulatory system in cardiac physiology and disease. Cardiovasc Res 73: 269-277, 2007.
53. Finck BN, Gropler MC, Chen Z, Leone TC, Croce MA, Harris TE, Lawrence JC Jr, Kelly DP. Lipin 1 is an inducible amplifier of the hepatic PGC-1alpha/PPARalpha regulatory pathway. Cell Metab 4: 199-210, 2006. (Pubitemid 44283957)
54. Finck BN, Han X, Courtois M, Aimond F, Nerbonne JM, Kovacs A, Gross RW, Kelly DP. A critical role for PPARalpha-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: modulation by dietary fat content. Proc Natl Acad Sci USA 100: 1226-1231, 2003.
55. Finck BN, Lehman JJ, Leone TC, Welch MJ, Bennett MJ, Kovacs A, Han X, Gross RW, Kozak R, Lopaschuk GD, Kelly DP. The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest 109: 121-130, 2002. (Pubitemid 34052548)
56. Fragasso G, Piatti Md PM, Monti L, Palloshi A, Setola E, Puccetti P, Calori G, Lopaschuk GD, Margonato A. Short- and long-term beneficial effects of trimetazidine in patients with diabetes and ischemic cardiomyopathy. Am Heart J 146: E18, 2003.
57. Gilde AJ, van der Lee KA, Willemsen PH, Chinetti G, van der Leij FR, van der Vusse GJ, Staels B, van Bilsen M. Peroxisome proliferator-activated receptor (PPAR) alpha and PPARbeta/delta, but not PPARgamma, modulate the expression of genes involved in cardiac lipid metabolism. Circ Res 92: 518-524, 2003. (Pubitemid 36368664)
58. Gilham D, Ho S, Rasouli M, Martres P, Vance DE, Lehner R. Inhibitors of hepatic microsomal triacylglycerol hydrolase decrease very low density lipoprotein secretion. FASEB J 17: 1685-1687, 2003.
59. Gimeno RE, Ortegon AM, Patel S, Punreddy S, Ge P, Sun Y, Lodish HF, Stahl A. Characterization of a heart-specific fatty acid transport protein. J Biol Chem 278: 16039-16044, 2003. (Pubitemid 36799724)
60. Ginsberg HN. Insulin resistance and cardiovascular disease. J Clin Invest 106: 453-458, 2000.
61. Glatz JF, Luiken JJ, Bonen A. Involvement of membrane-associated proteins in the acute regulation of cellular fatty acid uptake. J Mol Neurosci 16: 123-132; discussion 151-1127, 2001. (Pubitemid 32664771)
62. Gómez-Muñoz A, Hamza EH, Brindley DN. Effects of sphingosine, albumin and unsaturated fatty acids on the activation and translocation of phosphatidate phosphohydrolases in rat hepatocytes. Biochim Biophys Acta 1127: 49-56, 1992.
63. Gómez-Muñoz A, Hatch GM, Martin A, Jamal Z, Vance DE, Brindley DN. Effects of okadaic acid on the activities of two distinct phosphatidate phosphohydrolases in rat hepatocytes. FEBS Lett 301: 103-106, 1992.
64. Haemmerle G, Lass A, Zimmermann R, Gorkiewicz G, Meyer C, Rozman J, Heldmaier G, Maier R, Theussl C, Eder S, Kratky D, Wagner EF, Klingenspor M, Hoefler G, Zechner R. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 312: 734-737, 2006.
65. Haemmerle G, Zimmermann R, Hayn M, Theussl C, Waeg G, Wagner E, Sattler W, Magin TM, Wagner EF, Zechner R. Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J Biol Chem 277: 4806-4815, 2002. (Pubitemid 34968514)
66. Haemmerle G, Zimmermann R, Strauss JG, Kratky D, Riederer M, Knipping G, Zechner R. Hormone-sensitive lipase deficiency in mice changes the plasma lipid profile by affecting the tissue-specific expression pattern of lipoprotein lipase in adipose tissue and muscle. J Biol Chem 277: 12946-12952, 2002. (Pubitemid 34952662)
67. Han GS, Wu WI, Carman GM. The Saccharomyces cerevisiae Lipin homolog is a Mg2+-dependent phosphatidate phosphatase enzyme. J Biol Chem 281: 9210-9218, 2006.
68. Hanna AN, Berthiaume LG, Kikuchi Y, Begg D, Bourgoin S, Brindley DN. Tumor necrosis factor-alpha induces stress fiber formation through ceramide production: role of sphingosine kinase. Mol Biol Cell 12: 3618-3630, 2001.
69. Harris TE, Huffman TA, Chi A, Shabanowitz J, Hunt DF, Kumar A, Lawrence JC Jr. Insulin controls subcellular localization and multisite phosphorylation of the phosphatidic acid phosphatase, lipin 1. J Biol Chem 282: 277-286, 2007.
70. Herrero P, Peterson LR, McGill JB, Matthew S, Lesniak D, Dence C, Gropler RJ. Increased myocardial fatty acid metabolism in patients with type 1 diabetes mellitus. J Am Coll Cardiol 47: 598-604, 2006.
71. Hickson-Bick DL, Buja LM, McMillin JB. Palmitate-mediated alterations in the fatty acid metabolism of rat neonatal cardiac myocytes. J Mol Cell Cardiol 32: 511-519, 2000.
72. Hickson-Bick DL, Sparagna GC, Buja LM, McMillin JB. Palmitate-induced apoptosis in neonatal cardiomyocytes is not dependent on the generation of ROS. Am J Physiol Heart Circ Physiol 282: H656-H664, 2002.
73. Hirano K, Ikeda Y, Zaima N, Sakata Y, Matsumiya G. Triglyceride deposit cardiomyovasculopathy. N Engl J Med 359: 2396-2398, 2008.
74. Holm C, Belfrage P, Fredrikson G. Immunological evidence for the presence of hormone-sensitive lipase in rat tissues other than adipose tissue. Biochem Biophys Res Commun 148: 99-105, 1987.
75. Hübscher G, Brindley DN, Smith ME, Sedgwick B. Stimulation of biosynthesis of glyceride. Nature 216: 449-453, 1967.
76. Huss JM, Kelly DP. Nuclear receptor signaling and cardiac energetics. Circ Res 95: 568-578, 2004.
77. Iacobellis G, Barbaro G. The double role of epicardial adipose tissue as pro- and anti-inflammatory organ. Horm Metab Res 40: 442-445, 2008.
78. Ibrahimi A, Abumrad NA. Role of CD36 in membrane transport of long-chain fatty acids. Curr Opin Clin Nutr Metab Care 5: 139-145, 2002.
79. Jamal Z, Martin A, Gómez-Muñoz A, Hales P, Chang E, Russell JC, Brindley DN. Phosphatidate phosphohydrolases in liver, heart and adipose tissue of the JCR:LA corpulent rat and the lean genotypes: implications for glycerolipid synthesis and signal transduction. Int J Obes Relat Metab Disord 16: 789-799, 1992.
80. Karaskov E, Scott C, Zhang L, Teodoro T, Ravazzola M, Volchuk A. Chronic palmitate but not oleate exposure induces endoplasmic reticulum stress, which may contribute to INS-1 pancreatic beta-cell apoptosis. Endocrinology 147: 3398-3407, 2006.
81. Karlsson M, Contreras JA, Hellman U, Tornqvist H, Holm C. cDNA cloning, tissue distribution, and identification of the catalytic triad of monoglyceride lipase. Evolutionary relationship to esterases, lysophospholipases, and haloperoxidases. J Biol Chem 272: 27218-27223, 1997.
82. Khanderia U, Pop-Busui R, Eagle KA. Thiazolidinediones in type 2 diabetes: a cardiology perspective. Ann Pharmacother 42: 1466-1474, 2008.
83. Kim JY, van de Wall E, Laplante M, Azzara A, Trujillo ME, Hofmann SM, Schraw T, Durand JL, Li H, Li G, Jelicks LA, Mehler MF, Hui DY, Deshaies Y, Shulman GI, Schwartz GJ, Scherer PE. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J Clin Invest 117: 2621-2637, 2007.
84. Kong JY, Klassen SS, Rabkin SW. Ceramide activates a mitochondrial p38 mitogen-activated protein kinase: a potential mechanism for loss of mitochondrial transmembrane potential and apoptosis. Mol Cell Biochem 278: 39-51, 2005.
85. Koonen DP, Febbraio M, Bonnet S, Nagendran J, Young ME, Michelakis ED, Dyck JR. CD36 expression contributes to age-induced cardiomyopathy in mice. Circulation 116: 2139-2147, 2007.
86. Koonen DP, Glatz JF, Bonen A, Luiken JJ. Long-chain fatty acid uptake and FAT/CD36 translocation in heart and skeletal muscle. Biochim Biophys Acta 1736: 163-180, 2005.
87. Krown KA, Page MT, Nguyen C, Zechner D, Gutierrez V, Comstock KL, Glembotski CC, Quintana PJ, Sabbadini RA. Tumor necrosis factor alpha-induced apoptosis in cardiac myocytes. Involvement of the sphingolipid signaling cascade in cardiac cell death. J Clin Invest 98: 2854-2865, 1996. (Pubitemid 127541219)
88. Kusminski CM, Shetty S, Orci L, Unger RH, Scherer PE. Diabetes and apoptosis: lipotoxicity. Apoptosis 14: 1484-1495, 2009.
89. Levin MC, Monetti M, Watt MJ, Sajan MP, Stevens RD, Bain Jr, Newgard CB, Farese RV Sr, Farese RV Jr. Increased lipid accumulation and insulin resistance in transgenic mice expressing DGAT2 in glycolytic (type II) muscle. Am J Physiol Endocrinol Metab 293: E1772-E1781, 2007.
90. Lewin TM, de Jong H, Schwerbrock NJ, Hammond LE, Watkins SM, Combs TP, Coleman RA. Mice deficient in mitochondrial glycerol-3-phosphate acyltransferase-1 have diminished myocardial triacylglycerol accumulation during lipogenic diet and altered phospholipid fatty acid composition. Biochim Biophys Acta 1781: 352-358, 2008.
91. Lewis GF, Carpentier A, Adeli K, Giacca A. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev 23: 201-229, 2002. (Pubitemid 34299024)
92. Liang H, Ward WF. PGC-1α: a key regulator of energy metabolism. Adv Physiol Educ 30: 145-151, 2006.
93. Listenberger LL, Han X, Lewis SE, Cases S, Farese RV Jr, Ory DS, Schaffer JE. Triglyceride accumulation protects against fatty acidinduced lipotoxicity. Proc Natl Acad Sci USA 100: 3077-3082, 2003.
94. Listenberger LL, Ory DS, Schaffer JE. Palmitate-induced apoptosis can occur through a ceramide-independent pathway. J Biol Chem 276: 14890-14895, 2001.
95. Liu L, Shi X, Bharadwaj KG, Ikeda S, Yamashita H, Yagyu H, Schaffer JE, Yu YH, Goldberg IJ. DGAT1 expression increases heart triglyceride content but ameliorates lipotoxicity. J Biol Chem 284: 36312-36323, 2009.
96. Liu L, Shi X, Choi CS, Shulman GI, Klaus K, Nair KS, Schwartz GJ, Zhang Y, Goldberg IJ, Yu YH. Paradoxical coupling of triglyceride synthesis and fatty acid oxidation in skeletal muscle overexpressing DGAT1. Diabetes 58: 2516-2524, 2009.
97. Liu L, Zhang Y, Chen N, Shi X, Tsang B, Yu YH. Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance. J Clin Invest 117: 1679-1689, 2007.
98. Liu Q, Docherty JC, Rendell JC, Clanachan AS, Lopaschuk GD. High levels of fatty acids delay the recovery of intracellular pH and cardiac efficiency in post-ischemic hearts by inhibiting glucose oxidation. J Am Coll Cardiol 39: 718-725, 2002.
99. Lopaschuk G, Ussher J, Folmes C, Jaswal J, Stanley W. Myocardial fatty acid metabolism in health and disease. Physiol Rev 90: 207-258, 2010.
100. Lopaschuk GD, Barr R, Thomas PD, Dyck JR. Beneficial effects of trimetazidine in ex vivo working ischemic hearts are due to a stimulation of glucose oxidation secondary to inhibition of long-chain 3-ketoacyl coenzyme a thiolase. Circ Res 93: e33-e37, 2003.
101. 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 1213: 263-276, 1994.
102. Lu B, Jiang YJ, Zhou Y, Xu FY, Hatch GM, Choy PC. Cloning and characterization of murine 1-acyl-sn-glycerol 3-phosphate acyltransferases and their regulation by PPARalpha in murine heart. Biochem J 385: 469-477, 2005.
103. Luiken JJ. Sarcolemmal fatty acid uptake vs. mitochondrial betaoxidation as target to regress cardiac insulin resistance. Appl Physiol Nutr Metab 34: 473-480, 2009.
104. Luptak I, Balschi JA, Xing Y, Leone TC, Kelly DP, Tian R. Decreased contractile and metabolic reserve in peroxisome proliferatoractivated receptor-alpha-null hearts can be rescued by increasing glucose transport and utilization. Circulation 112: 2339-2346, 2005.
105. Manmontri B, Sariahmetoglu M, Donkor J, Khalil MB, Sundaram M, Yao Z, Reue K, Lehner R, Brindley DN. Glucocorticoids and cyclic AMP selectively increase hepatic lipin-1 expression, and insulin acts antagonistically. J Lipid Res 49: 1056-1067, 2008.
106. Martin G, Schoonjans K, Lefebvre AM, Staels B, Auwerx J. Coordinate regulation of the expression of the fatty acid transport protein and acyl-CoA synthetase genes by PPARalpha and PPARgamma activators. J Biol Chem 272: 28210-28217, 1997.
107. Martin-Sanz P, Vance JE, Brindley DN. Stimulation of apolipoprotein secretion in very-low-density and high-density lipoproteins from cultured rat hepatocytes by dexamethasone. Biochem J 271: 575-583, 1990.
108. Mashek DG, Coleman RA. Cellular fatty acid uptake: the contribution of metabolism. Curr Opin Lipidol 17: 274-278, 2006.
109. Mazumder PK, O'Neill BT, Roberts MW, Buchanan J, Yun UJ, Cooksey RC, Boudina S, Abel ED. Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts. Diabetes 53: 2366-2374, 2004.
110. McArthur MD, Graham SE, Russell JC, Brindley DN. Exaggerated stress-induced release of nonesterified fatty acids in JCR:LA-corpulent rats. Metabolism 47: 1383-1390, 1998.
111. Miller TA, LeBrasseur NK, Cote GM, Trucillo MP, Pimentel DR, Ido Y, Ruderman NB, Sawyer DB. Oleate prevents palmitate-induced cytotoxic stress in cardiac myocytes. Biochem Biophys Res Commun 336: 309-315, 2005.
112. Montell E, Turini M, Marotta M, Roberts M, Noe V, Ciudad CJ, Mace K, Gomez-Foix AM. DAG accumulation from saturated fatty acids desensitizes insulin stimulation of glucose uptake in muscle cells. Am J Physiol Endocrinol Metab 280: E229-E237, 2001.
113. Morino K, Neschen S, Bilz S, Sono S, Tsirigotis D, Reznick RM, Moore I, Nagai Y, Samuel V, Sebastian D, White M, Philbrick W, Shulman GI. Muscle-specific IRS-1 Ser->Ala transgenic mice are protected from fat-induced insulin resistance in skeletal muscle. Diabetes 57: 2644-2651, 2008.
114. Mougios V, Ring S, Petridou A, Nikolaidis MG. Duration of coffee- and exercise-induced changes in the fatty acid profile of human serum. J Appl Physiol 94: 476-484, 2003. (Pubitemid 36158221)
115. Murray AJ, Panagia M, Hauton D, Gibbons GF, Clarke K. Plasma free fatty acids and peroxisome proliferator-activated receptor alpha in the control of myocardial uncoupling protein levels. Diabetes 54: 3496-3502, 2005.
116. O'Meara E, McMurray JJ. Myocardial metabolic manipulation: a new therapeutic approach in heart failure? Heart 91: 131-132, 2005.
117. Okere IC, Chandler MP, McElfresh TA, Rennison JH, Sharov V, Sabbah HN, Tserng KY, Hoit BD, Ernsberger P, Young ME, Stanley WC. Differential effects of saturated and unsaturated fatty acid diets on cardiomyocyte apoptosis, adipose distribution, and serum leptin. Am J Physiol Heart Circ Physiol 291: H38-H44, 2006.
118. Ostrander DB, Sparagna GC, Amoscato AA, McMillin JB, Dowhan W. Decreased cardiolipin synthesis corresponds with cytochrome c release in palmitate-induced cardiomyocyte apoptosis. J Biol Chem 276: 38061-38067, 2001.
119. Ouwens DM, Diamant M, Fodor M, Habets DD, Pelsers MM, El Hasnaoui M, Dang ZC, van den Brom CE, Vlasblom R, Rietdijk A, Boer C, Coort SL, Glatz JF, Luiken JJ. Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification. Diabetologia 50: 1938-1948, 2007.
120. Park SY, Kim HJ, Wang S, Higashimori T, Dong J, Kim YJ, Cline G, Li H, Prentki M, Shulman GI, Mitchell GA, Kim JK. Hormonesensitive lipase knockout mice have increased hepatic insulin sensitivity and are protected from short-term diet-induced insulin resistance in skeletal muscle and heart. Am J Physiol Endocrinol Metab 289: E30-E39, 2005.
121. Park TS, Yamashita H, Blaner WS, Goldberg IJ. Lipids in the heart: a source of fuel and a source of toxins. Curr Opin Lipidol 18: 277-282, 2007.
122. Parra V, Eisner V, Chiong M, Criollo A, Moraga F, Garcia A, Hartel S, Jaimovich E, Zorzano A, Hidalgo C, Lavandero S. Changes in mitochondrial dynamics during ceramide-induced cardiomyocyte early apoptosis. Cardiovasc Res 77: 387-397, 2008.
123. Peterfy M, Harris TE, Fujita N, Reue K. Insulin-stimulated interaction with 14-3-3 promotes cytoplasmic localization of lipin-1 in adipocytes. J Biol Chem Dec 2. [Epub ahead of print] PMID: 19955570.
124. Phan J, Reue K. Lipin, a lipodystrophy and obesity gene. Cell Metab 1: 73-83, 2005.
125. Pittner RA, Fears R, Brindley DN. Interactions of insulin, glucagon and dexamethasone in controlling the activity of glycerol phosphate acyltransferase and the activity and subcellular distribution of phosphatidate phosphohydrolase in cultured rat hepatocytes. Biochem J 230: 525-534, 1985.
126. Powell DJ, Turban S, Gray A, Hajduch E, Hundal HS. Intracellular ceramide synthesis and protein kinase Czeta activation play an essential role in palmitate-induced insulin resistance in rat L6 skeletal muscle cells. Biochem J 382: 619-629, 2004.
127. Pruimboom-Brees I, Haghpassand M, Royer L, Brees D, Aldinger C, Reagan W, Singh J, Kerlin R, Kane C, Bagley S, Hayward C, Loy J, O'Brien P, Francone OL. A critical role for peroxisomal proliferator-activated receptor-alpha nuclear receptors in the development of cardiomyocyte degeneration and necrosis. Am J Pathol 169: 750-760, 2006.
128. Pulinilkunnil T, Rodrigues B. Cardiac lipoprotein lipase: metabolic basis for diabetic heart disease. Cardiovasc Res 69: 329-340, 2006.
129. Reddy JK, Rao MS. Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am J Physiol Gastrointest Liver Physiol 290: G852-G858, 2006.
130. Regan TJ, Ahmed S, Haider B, Moschos C, Weisse A. Diabetic cardiomyopathy: experimental and clinical observations. N J Med 91: 776-778, 1994.
131. Reue K, Brindley DN. Thematic Review Series: Glycerolipids. Multiple roles for lipins/phosphatidate phosphatase enzymes in lipid metabolism. J Lipid Res 49: 2493-2503, 2008.
132. Reue K, Zhang P. The lipin protein family: dual roles in lipid biosynthesis and gene expression. FEBS Lett 582: 90-96, 2008.
133. Russell LK, Finck BN, Kelly DP. Mouse models of mitochondrial dysfunction and heart failure. J Mol Cell Cardiol 38: 81-91, 2005.
134. Sabbah HN, Chandler MP, Mishima T, Suzuki G, Chaudhry P, Nass O, Biesiadecki BJ, Blackburn B, Wolff A, Stanley WC. Ranolazine, a partial fatty acid oxidation (pFOX) inhibitor, improves left ventricular function in dogs with chronic heart failure. J Card Fail 8: 416-422, 2002.
135. Saddik M, Lopaschuk GD. Myocardial triglyceride turnover during reperfusion of isolated rat hearts subjected to a transient period of global ischemia. J Biol Chem 267: 3825-3831, 1992.
136. Saggerson ED. Phosphatidate Phosphohydrolase: Its Role in Glycerolipid Synthesis. Boca Raton, FL: CRC, 1988.
137. Sambandam N, Morabito D, Wagg C, Finck BN, Kelly DP, Lopaschuk GD. Chronic activation of PPARα is detrimental to cardiac recovery after ischemia. Am J Physiol Heart Circ Physiol 290: H87-H95, 2006.
138. Schaffer JE. Lipotoxicity: when tissues overeat. Curr Opin Lipidol 14: 281-287, 2003.
139. Schoonderwoerd K, Broekhoven-Schokker S, Hulsmann WC, Stam H. Properties of phosphatidate phosphohydrolase and diacylglycerol acyltransferase activities in the isolated rat heart. Effect of glucagon, ischaemia and diabetes. Biochem J 268: 487-492, 1990. (Pubitemid 20193993)
140. Schweiger M, Lass A, Zimmermann R, Eichmann TO, Zechner R. Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2 or CGI-58/ABHD5. Am J Physiol Endocrinol Metab 297: E289-E296, 2009.
141. Shen X, Zheng S, Metreveli NS, Epstein PN. Protection of cardiac mitochondria by overexpression of MnSOD reduces diabetic cardiomyopathy. Diabetes 55: 798-805, 2006. (Pubitemid 43343239)
142. Shen X, Zheng S, Thongboonkerd V, Xu M, PierceWMJr, Klein JB, Epstein PN. Cardiac mitochondrial damage and biogenesis in a chronic model of type 1 diabetes. Am J Physiol Endocrinol Metab 287: E896-E905, 2004.
143. Shimabukuro M, Higa M, Zhou YT, Wang MY, Newgard CB, Unger RH. Lipoapoptosis in beta-cells of obese prediabetic fa/fa rats. Role of serine palmitoyltransferase overexpression. J Biol Chem 273: 32487-32490, 1998.
144. Sparagna GC, Hickson-Bick DL, Buja LM, McMillin JB. 5A metabolic role for mitochondria in palmitate-induced cardiac myocyte apoptosis. Am J Physiol Heart Circ Physiol 279: H2124-H2132, 2000.
145. Stanley WC, Chandler MP. Energy metabolism in the normal and failing heart: potential for therapeutic interventions. Heart Fail Rev 7: 115-130, 2002.
146. Stanley WC, Recchia FA, Lopaschuk GD. Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 85: 1093-1129, 2005.
147. Suzuki J, Shen WJ, Nelson BD, Patel S, Veerkamp JH, Selwood SP, Murphy GM Jr, Reaven E, Kraemer FB. Absence of cardiac lipid accumulation in transgenic mice with heart-specific HSL overexpression. Am J Physiol Endocrinol Metab 281: E857-E866, 2001.
148. Swanton EM, Saggerson ED. Glycerolipid metabolizing enzymes in rat ventricle and in cardiac myocytes. Biochim Biophys Acta 1346: 93-102, 1997.
149. Szczepaniak LS, Victor RG, Orci L, Unger RH. Forgotten but not gone: the rediscovery of fatty heart, the most common unrecognized disease in America. Circ Res 101: 759-767, 2007.
150. Taegtmeyer H. Cardiac metabolism as a target for the treatment of heart failure. Circulation 110: 894-896, 2004. (Pubitemid 39128613)
151. Takeuchi K, Reue K. Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis. Am J Physiol Endocrinol Metab 296: E1195-E1209, 2009.
152. Tomita T, Wilson L, Chiga M. Idiopathic dilated cardiomyopathy - an evidence of abnormal lipid accumulation accumulation in myocardium. Am J Cardiovasc Pathol 3: 81-85, 1990.
153. Ueno M, Suzuki J, Zenimaru Y, Takahashi S, Koizumi T, Noriki S, Yamaguchi O, Otsu K, Shen WJ, Kraemer FB, Miyamori I. Cardiac overexpression of hormone-sensitive lipase inhibits myocardial steatosis and fibrosis in streptozotocin diabetic mice. Am J Physiol Endocrinol Metab 294: E1109-E1118, 2008.
154. Unger RH. Hyperleptinemia: protecting the heart from lipid overload. Hypertension 45: 1031-1034, 2005.
155. Unger RH. Lipotoxic diseases. Annu Rev Med 53: 319-336, 2002.
156. Unger RH, Orci L. Lipotoxic diseases of nonadipose tissues in obesity. Int J Obes Relat Metab Disord 24, Suppl 4: S28-32, 2000.
157. Unger RH, Zhou YT. Lipotoxicity of beta-cells in obesity and in other causes of fatty acid spillover. Diabetes 50, Suppl 1: S118-S121, 2001.
158. Unger RH, Zhou YT, Orci L. Regulation of fatty acid homeostasis in cells: novel role of leptin. Proc Natl Acad Sci USA 96: 2327-2332, 1999.
159. van der Vusse GJ, Glatz JF, Stam HC, Reneman RS. Fatty acid homeostasis in the normoxic and ischemic heart. Physiol Rev 72: 881-940, 1992.
160. van Herpen NA, Schrauwen-Hinderling VB. Lipid accumulation in non-adipose tissue and lipotoxicity. Physiol Behav 94: 231-241, 2008.
161. Vitale C, Wajngaten M, Sposato B, Gebara O, Rossini P, Fini M, Volterrani M, Rosano GM. Trimetazidine improves left ventricular function and quality of life in elderly patients with coronary artery disease. Eur Heart J 25: 1814-1821, 2004.
162. Wang CN, McLeod RS, Yao Z, Brindley DN. Effects of dexamethasone on the synthesis, degradation, and secretion of apolipoprotein B in cultured rat hepatocytes. Arterioscler Thromb Vasc Biol 15: 1481-1491, 1995.
163. Wang CN, O'Brien L, Brindley DN. Effects of cell-permeable ceramides and tumor necrosis factor-alpha on insulin signaling and glucose uptake in 3T3-L1 adipocytes. Diabetes 47: 24-31, 1998.
164. Watt MJ. Triglyceride lipases alter fuel metabolism and mitochondrial gene expression. Appl Physiol Nutr Metab 34: 340-347, 2009.
165. Watt MJ, van Denderen BJ, Castelli LA, Bruce CR, Hoy AJ, Kraegen EW, Macaulay L, Kemp BE. Adipose triglyceride lipase regulation of skeletal muscle lipid metabolism and insulin responsiveness. Mol Endocrinol 22: 1200-1212, 2008.
166. Wei E, Alam M, Sun F, Agellon LB, Vance DE, Lehner R. Apolipoprotein B and triacylglycerol secretion in human triacylglycerol hydrolase transgenic mice. J Lipid Res 48: 2597-2606, 2007.
167. Wei Y, Wang D, Topczewski F, Pagliassotti MJ. Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells. Am J Physiol Endocrinol Metab 291: E275-E281, 2006. (Pubitemid 44035286)
168. Wende AR, Abel ED. Lipotoxicity in the heart. Biochim Biophys Acta, 2009.
169. Whiting PH, Bowley M, Sturton RG, Pritchard PH, Brindley DN, Hawthorne JN. The effect of chronic diabetes, induced by streptozotocin, on the activities of some enzymes of glycerolipid synthesis in rat liver. Biochem J 168: 147-153, 1977. (Pubitemid 8224065)
170. Yagyu H, Chen G, Yokoyama M, Hirata K, Augustus A, Kako Y, Seo T, Hu Y, Lutz EP, Merkel M, Bensadoun A, Homma S, Goldberg IJ. Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy. J Clin Invest 111: 419-426, 2003. (Pubitemid 36182219)
171. Ye G, Metreveli NS, Ren J, Epstein PN. Metallothionein prevents diabetes-induced deficits in cardiomyocytes by inhibiting reactive oxygen species production. Diabetes 52: 777-783, 2003. (Pubitemid 36323586)
172. Yeaman SJ. Hormone-sensitive lipase-new roles for an old enzyme. Biochem J 379: 11-22, 2004.
173. Yen CL, Stone SJ, Koliwad S, Harris C, Farese RV Jr. Thematic Review Series: Glycerolipids. DGAT enzymes and triacylglycerol biosynthesis. J Lipid Res 49: 2283-2301, 2008.
174. Young ME, Guthrie PH, Razeghi P, Leighton B, Abbasi S, Patil S, Youker KA, Taegtmeyer H. Impaired long-chain fatty acid oxidation and contractile dysfunction in the obese Zucker rat heart. Diabetes 51: 2587-2595, 2002. (Pubitemid 34827411)
175. Zammit VA, Buckett LK, Turnbull AV, Wure H, Proven A. Diacylglycerol acyltransferases: potential roles as pharmacological targets. Pharmacol Ther 118: 295-302, 2008.
176. Zechner R, Kienesberger PC, Haemmerle G, Zimmermann R, Lass A. Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. J Lipid Res 50: 3-21, 2009.
177. Zhang P, O'Loughlin L, Brindley D, Reue K. Regulation of lipin-1 gene expression by glucocorticoids during adipogenesis. J Lipid Res 49: 1519-1528, 2008.
178. Zhou YT, Grayburn P, Karim A, Shimabukuro M, Higa M, Baetens D, Orci L, Unger RH. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci USA 97: 1784-1789, 2000.
179. Zinn A, Felson S, Fisher E, Schwartzbard A. Reassessing the cardiovascular risks and benefits of thiazolidinediones. Clin Cardiol 31: 397-403, 2008.