Lipid-induced cardiovascular diseases
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Abstract
Cardiovascular diseases are the leading cause of death worldwide. There are many evidences that the dysfunctioning lipotoxicity is the one of major factors of cardiovascular diseases such as, atherosclerosis, hypertension, and coronary heart disease. Obesity and diabetes increase circulating lipids that are likely with more generation of toxic intermediates, which leading to the complications associated with cardiovascular diseases. Indeed, lipotoxicity is a metabolic syndrome caused by abnormal lipid accumulation, which leads to cellular dysfunction and necrosis. Here we review the factors that induced pathogenesis of cardiovascular diseases by lipid accumulation and the mechanisms underlying the lipotoxicity.
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Mattes RD. Fat taste and lipid metabolism in humans. Physiol Behav. 2005; 86: 691-697. Ref: https://goo.gl/nN6YSn DOI: https://doi.org/10.1016/j.physbeh.2005.08.058
Schaffer JE. Lipotoxicity: when tissues overeat. Curr Opin Lipidol. 2003; 14: 281-287. Ref: https://goo.gl/ScoErq DOI: https://doi.org/10.1097/00041433-200306000-00008
Alshehri AM. Metabolic syndrome and cardiovascular risk. J Family Community Med. 2010; 17: 73-78. Ref: https://goo.gl/d8mLvy DOI: https://doi.org/10.4103/1319-1683.71987
Chavez JA,Summers SA. Lipid oversupply. selective insulin resistance, and lipotoxicity: molecular mechanisms. Biochim Biophys Acta. 2010; 1801: 252-265. Ref: https://goo.gl/YB4P7f DOI: https://doi.org/10.1016/j.bbalip.2009.09.015
Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001; 24: 683-689. Ref: https://goo.gl/KRiXB2 DOI: https://doi.org/10.2337/diacare.24.4.683
Laaksonen DE, Lakka HM, Niskanen LK, Kaplan GA, Salonen JT, et al. Metabolic syndrome and development of diabetes mellitus: application and validation of recently suggested definitions of the metabolic syndrome in a prospective cohort study. Am J Epidemiol. 2002; 156: 1070-1077. Ref: https://goo.gl/5mcBbN DOI: https://doi.org/10.1093/aje/kwf145
Turpin SM, Ryall JG, Southgate R, Darby I, Hevener AL, et al. Examination of 'lipotoxicity' in skeletal muscle of high-fat fed and ob/ob mice. J Physiol. 2009; 587: 1593-1605. Ref: https://goo.gl/npCrgA DOI: https://doi.org/10.1113/jphysiol.2008.166033
Winzell MS, Svensson H, Enerback S, Ravnskjaer K, Mandrup S, et al. Pancreatic beta-cell lipotoxicity induced by overexpression of hormone-sensitive lipase. Diabetes. 2003; 52: 2057-2065. Ref: https://goo.gl/obLxVH DOI: https://doi.org/10.2337/diabetes.52.8.2057
Shimabukuro M, Zhou YT, Levi M, Unger RH. Fatty acid-induced beta cell apoptosis: a link between obesity and diabetes. Proc Natl Acad Sci USA. 1998; 95: 2498-2502. Ref: https://goo.gl/djrqfD DOI: https://doi.org/10.1073/pnas.95.5.2498
Prentki M, Joly E, El-Assaad W,Roduit R, Malonyl-CoA signaling, lipid partitioning, and glucolipotoxicity: role in beta-cell adaptation and failure in the etiology of diabetes. Diabetes. 2002; 51: 405-413. Ref: https://goo.gl/bnLzvh DOI: https://doi.org/10.2337/diabetes.51.2007.S405
Lupi R, Dotta F, Marselli L, Del Guerra S, Masini M, et al. Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets: evidence that beta-cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated. Diabetes. 2002; 51: 1437-1442. Ref: https://goo.gl/BgdR6t DOI: https://doi.org/10.2337/diabetes.51.5.1437
Robertson RP, Harmon J, Tran PO,Poitout V, Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes. 2004; 53: 119-124. Ref: https://goo.gl/Xif2YQ DOI: https://doi.org/10.2337/diabetes.53.2007.S119
Trauner M, Arrese M,Wagner M, Fatty liver and lipotoxicity. Biochim Biophys Acta. 2010; 1801: 299-310. Ref: https://goo.gl/8xD98d DOI: https://doi.org/10.1016/j.bbalip.2009.10.007
Ibdah JA, Paul H, Zhao Y, Binford S, Salleng K, et al. Lack of mitochondrial trifunctional protein in mice causes neonatal hypoglycemia and sudden death. J Clin Invest. 2001; 107: 1403-1409. Ref: https://goo.gl/WvQCb8 DOI: https://doi.org/10.1172/JCI12590
Bobulescu IA, Renal lipid metabolism and lipotoxicity. Curr Opin Nephrol Hypertens. 2010; 19: 393-402. Ref: https://goo.gl/CpBSf2 DOI: https://doi.org/10.1097/MNH.0b013e32833aa4ac
Kim JA, Montagnani M, Chandrasekran S,Quon MJ. Role of lipotoxicity in endothelial dysfunction. Heart Fail Clin. 2012; 8: 589-607. Ref: https://goo.gl/SbMja6 DOI: https://doi.org/10.1016/j.hfc.2012.06.012
Nichols M, Townsend N, Scarborough P, Rayner M. Cardiovascular disease in Europe 2014: epidemiological update. Eur Heart J. 2014; 2950-2959. Ref: DOI: https://doi.org/10.1093/eurheartj/ehu299
Abel ED, Litwin SE,Sweeney G, Cardiac remodeling in obesity. Physiol Rev. 2008; 88: 389-419. Ref: https://goo.gl/jh2U9f DOI: https://doi.org/10.1152/physrev.00017.2007
Kenchaiah S, Evans JC, Levy D, Wilson PW, Benjamin EJ, et al. Obesity and the risk of heart failure. N Engl J Med. 2002; 347: 305-313. Ref: https://goo.gl/AazmFW DOI: https://doi.org/10.1056/NEJMoa020245
Dyntar D, Eppenberger-Eberhardt M, Maedler K, Pruschy M, Eppenberger HM, et al. Glucose and palmitic acid induce degeneration of myofibrils and modulate apoptosis in rat adult cardiomyocytes. Diabetes. 2001; 50: 2105-2113. Ref: https://goo.gl/sJsYL8 DOI: https://doi.org/10.2337/diabetes.50.9.2105
DeFronzo RA, Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia. 2010; 53: 1270-1287. Ref: https://goo.gl/sRDzGc DOI: https://doi.org/10.1007/s00125-010-1684-1
Wende AR,Abel ED, Lipotoxicity in the heart. Biochim Biophys Acta. 2010; 1801: 311-319. Ref: https://goo.gl/RZ2tSC DOI: https://doi.org/10.1016/j.bbalip.2009.09.023
Goldberg IJ, Trent CM,Schulze PC, Lipid metabolism and toxicity in the heart. Cell Metab. 2012; 15: 805-812. Ref: https://goo.gl/Jb72N7 DOI: https://doi.org/10.1016/j.cmet.2012.04.006
Yagyu H, Chen G, Yokoyama M, Hirata K, Augustus A, et al. Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy. J Clin Invest. 2003; 111: 419-426. Ref: https://goo.gl/MFauH3 DOI: https://doi.org/10.1172/JCI16751
Park TS, Hu Y, Noh HL, Drosatos K, Okajima K, et al. Ceramide is a cardiotoxin in lipotoxic cardiomyopathy. J Lipid Res. 2008; 49: 2101-2112. Ref: https://goo.gl/rALwnF DOI: https://doi.org/10.1194/jlr.M800147-JLR200
Halton TL, Willett WC, Liu S, Manson JE, Albert CM, et al. Low-carbohydrate-diet score and the risk of coronary heart disease in women. N Engl J Med. 2006; 355: 1991-2002. Ref: https://goo.gl/NvdZ6S DOI: https://doi.org/10.1056/NEJMoa055317
Hu FB,Willett WC, Optimal diets for prevention of coronary heart disease. JAMA. 2002; 288: 2569-2578. Ref: https://goo.gl/qgXQY9 DOI: https://doi.org/10.1001/jama.288.20.2569
Lavie CJ, Milani RV, Mehra MR,Ventura HO, Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J Am Coll Cardiol. 2009; 54: 585-594. Ref: https://goo.gl/QNpSqw DOI: https://doi.org/10.1016/j.jacc.2009.02.084
Mozaffarian D,Wu JH, Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol. 2011; 58: 2047-2067. Ref: https://goo.gl/t66E6q DOI: https://doi.org/10.1016/j.jacc.2011.06.063
Young ME, Guthrie PH, Razeghi P, Leighton B, Abbasi S, et al. Impaired long-chain fatty acid oxidation and contractile dysfunction in the obese Zucker rat heart. Diabetes. 2002; 51: 2587-2595. Ref: https://goo.gl/aj1MRb DOI: https://doi.org/10.2337/diabetes.51.8.2587
Sharma S, Adrogue JV, Golfman L, Uray I, Lemm J, et al. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. Faseb j. 2004; 1692-1700. Ref: https://goo.gl/dPWBiw DOI: https://doi.org/10.1096/fj.04-2263com
Watson KE, Peters Harmel AL,Matson G. Atherosclerosis in type 2 diabetes mellitus: the role of insulin resistance. J Cardiovasc Pharmacol Ther. 2003; 253-260. Ref: https://goo.gl/gPizLV DOI: https://doi.org/10.1177/107424840300800402
Kelley DE. Skeletal muscle fat oxidation: timing and flexibility are everything. J Clin Invest. 2005; 1699-1702. Ref: https://goo.gl/RcohyL DOI: https://doi.org/10.1172/JCI25758
Terrand J, Bruban V, Zhou L, Gong W, El Asmar Z, et al. LRP1 controls intracellular cholesterol storage and fatty acid synthesis through modulation of Wnt signaling. J Biol Chem. 2009; 381-388. Ref: https://goo.gl/CCydTp DOI: https://doi.org/10.1074/jbc.M806538200
Alexander RW. Theodore Cooper Memorial Lecture. Hypertension and the pathogenesis of atherosclerosis. Oxidative stress and the mediation of arterial inflammatory response: a new perspective. Hypertension. 1995; 155-161. Ref: https://goo.gl/9Rd8uC DOI: https://doi.org/10.1161/01.HYP.25.2.155
Hemnes AR, Brittain EL, Trammell AW, Fessel JP, Austin ED, et al. Evidence for right ventricular lipotoxicity in heritable pulmonary arterial hypertension. Am J Respir Crit Care Med. 2014; 325-334. Ref: https://goo.gl/b6Ua5j DOI: https://doi.org/10.1164/rccm.201306-1086OC
Zhao X. Prevention of local lipotoxicity: a new renoprotective mechanism of peroxisome proliferator-activated receptor-alpha activation in hypertension and obesity? Hypertens Res. 2009; 821-823. Ref: https://goo.gl/T7CDLj DOI: https://doi.org/10.1038/hr.2009.128
Kelly DP, Hale DE, Rutledge SL, Ogden ML, Whelan AJ, et al. Molecular basis of inherited medium-chain acyl-CoA dehydrogenase deficiency causing sudden child death. J Inherit Metab Dis. 1992; 171-180. Ref: https://goo.gl/FPmU8b DOI: https://doi.org/10.1007/BF01799626
Kurtz DM, Rinaldo P, Rhead WJ, Tian L, Millington DS, et al. Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation. Proc Natl Acad Sci USA. 1998; 15592-15597.Ref: https://goo.gl/DqxeyC DOI: https://doi.org/10.1073/pnas.95.26.15592
Drosatos K, Schulze PC. Cardiac lipotoxicity: molecular pathways and therapeutic implications. Curr Heart Fail Rep. 2013; 109-121. Ref: https://goo.gl/qyGyci DOI: https://doi.org/10.1007/s11897-013-0133-0
Hickson-Bick DL, Buja LM, McMillin JB. Palmitate-mediated alterations in the fatty acid metabolism of rat neonatal cardiac myocytes. J Mol Cell Cardiol. 2000; 511-519. Ref: https://goo.gl/1se7ws DOI: https://doi.org/10.1006/jmcc.1999.1098
Sparagna GC, Hickson-Bick DL, Buja LM, McMillin JB. A metabolic role for mitochondria in palmitate-induced cardiac myocyte apoptosis. Am J Physiol Heart Circ Physiol. 2000; H2124-2132.Ref: https://goo.gl/rUwtzX DOI: https://doi.org/10.1152/ajpheart.2000.279.5.H2124
Dbaibo GS, Pushkareva MY, Rachid RA, Alter N, Smyth MJ, et al. p53-dependent ceramide response to genotoxic stress. J Clin Invest.1998; 102: 329-339.Ref: https://goo.gl/mBJUV5 DOI: https://doi.org/10.1172/JCI1180
Rotolo JA, Zhang J, Donepudi M, Lee H, Fuks Z, et al. Caspase-dependent and -independent activation of acid sphingomyelinase signaling. J Biol Chem. 2005; 26425-26434. Ref: https://goo.gl/WaV9Fu DOI: https://doi.org/10.1074/jbc.M414569200
Dbaibo GS, El-Assaad W, Krikorian A, Liu B, Diab K, et al. Ceramide generation by two distinct pathways in tumor necrosis factor alpha-induced cell death. FEBS Lett. 2001; 7-12. Ref: https://goo.gl/JYXgJj DOI: https://doi.org/10.1016/S0014-5793(01)02625-4
Quillet-Mary A, Jaffrezou JP, Mansat V, Bordier C, Naval J, et al. Implication of mitochondrial hydrogen peroxide generation in ceramide-induced apoptosis. J Biol Chem. 1997; 21388-21395.Ref: https://goo.gl/TnhYZ4 DOI: https://doi.org/10.1074/jbc.272.34.21388
Siskind LJ. Mitochondrial ceramide and the induction of apoptosis. J Bioenerg Biomembr. 2005; 143-153. Ref: https://goo.gl/1RMjof DOI: https://doi.org/10.1007/s10863-005-6567-7
Weiss B, Stoffel W. Human and murine serine-palmitoyl-CoA transferase--cloning, expression and characterization of the key enzyme in sphingolipid synthesis. Eur J Biochem. 1997; 239-247.Ref: https://goo.gl/HB7Yc7 DOI: https://doi.org/10.1111/j.1432-1033.1997.00239.x
Shimabukuro M, Higa M, Zhou YT, Wang MY, Newgard CB, et al. Lipoapoptosis in beta-cells of obese prediabetic fa/fa rats. Role of serine palmitoyltransferase overexpression. J Biol Chem. 1998; 32487-32490.Ref: https://goo.gl/o9DBkr DOI: https://doi.org/10.1074/jbc.273.49.32487
Merrill AH, Jr. De novo sphingolipid biosynthesis: a necessary, but dangerous, pathway. J Biol Chem. 2002; 25843-25846. Ref: https://goo.gl/xy7cMM DOI: https://doi.org/10.1074/jbc.R200009200
Haimovitz-Friedman A, Kan CC, Ehleiter D, Persaud RS, McLoughlin M, et al. Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J Exp Med. 1994; 525-535.Ref: https://goo.gl/ahzCL7 DOI: https://doi.org/10.1084/jem.180.2.525
Hardie DG, Carling D,Carlson M. The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell? Annu Rev Biochem. 1998; 821-855. Ref: https://goo.gl/tP4hP3 DOI: https://doi.org/10.1146/annurev.biochem.67.1.821
Chabowski A, Momken I, Coort SL, Calles-Escandon J, Tandon NN, et al. Prolonged AMPK activation increases the expression of fatty acid transporters in cardiac myocytes and perfused hearts. Mol Cell Biochem. 2006; 201-212. Ref: https://goo.gl/E4DPKj DOI: https://doi.org/10.1007/s11010-006-9140-8
Habets DD, Coumans WA, Voshol PJ, den Boer MA, Febbraio M, et al. AMPK-mediated increase in myocardial long-chain fatty acid uptake critically depends on sarcolemmal CD36. Biochem Biophys Res Commun. 2007; 204-210.Ref: https://goo.gl/Qo1fFp DOI: https://doi.org/10.1016/j.bbrc.2007.01.141
Finck BN, Lehman JJ, Leone TC, Welch MJ, Bennett MJ, et al. The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest. 2002; 121-130.Ref: https://goo.gl/Tgo6Jk DOI: https://doi.org/10.1172/JCI200214080
Vega RB, Huss JM, Kelly DP. The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol, 2000; 1868-1876. Ref: https://goo.gl/1XuSzq DOI: https://doi.org/10.1128/MCB.20.5.1868-1876.2000
Karbowska J, Kochan Z, Smolenski RT. Peroxisome proliferator-activated receptor alpha is downregulated in the failing human heart. Cell Mol Biol Lett. 2003; 49-53. Ref: https://goo.gl/zfFVAu
Masamura K, Tanaka N, Yoshida M, Kato M, Kawai Y, et al. Myocardial metabolic regulation through peroxisome proliferator-activated receptor alpha after myocardial infarction. Exp Clin Cardiol. 2003; 61-66. Ref: https://goo.gl/LPRDH7
Narravula S,Colgan SP. Hypoxia-inducible factor 1-mediated inhibition of peroxisome proliferator-activated receptor alpha expression during hypoxia. J Immunol. 2001; 7543-7548. Ref: https://goo.gl/pvsQDV DOI: https://doi.org/10.4049/jimmunol.166.12.7543
Aoyama T, Peters JM, Iritani N, Nakajima T, Furihata K, et al. Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor alpha (PPARalpha). J Biol Chem. 1998; 5678-5684. Ref: https://goo.gl/6N7BKG DOI: https://doi.org/10.1074/jbc.273.10.5678
Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, 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. 1995; 3012-3022. Ref: https://goo.gl/EVfL3d DOI: https://doi.org/10.1128/MCB.15.6.3012
Kersten S. Peroxisome proliferator activated receptors and lipoprotein metabolism. PPAR Res. 2008; 132960. Ref: https://goo.gl/vmxnLo DOI: https://doi.org/10.1155/2008/132960
Yoon M. PPARalpha in Obesity: Sex Difference and Estrogen Involvement. PPAR Res. 2010. Ref: https://goo.gl/dFMJ2x DOI: https://doi.org/10.1155/2010/584296
Inoguchi T, Battan R, Handler E, Sportsman JR, Heath W, et al. Preferential elevation of protein kinase C isoform beta II and diacylglycerol levels in the aorta and heart of diabetic rats: differential reversibility to glycemic control by islet cell transplantation. Proc Natl Acad Sci U S A. 1992; 11059-11063. Ref: https://goo.gl/49QxVc DOI: https://doi.org/10.1073/pnas.89.22.11059
Jalili T, Manning J,Kim S. Increased translocation of cardiac protein kinase C beta2 accompanies mild cardiac hypertrophy in rats fed saturated fat. J Nutr. 2003; 358-361. Ref: https://goo.gl/E9WeXu DOI: https://doi.org/10.1093/jn/133.2.358
Fujino T, Asaba H, Kang MJ, Ikeda Y, Sone H, et al. Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion. Proc Natl Acad Sci U S A. 2003; 229-234. Ref: https://goo.gl/TzbGv6 DOI: https://doi.org/10.1073/pnas.0133792100
Kim DH, Cho YM, Lee KH, Jeong SW,Kwon OJ. Oleate protects macrophages from palmitate-induced apoptosis through the downregulation of CD36 expression. Biochem Biophys Res Commun. 2017; 477-482. Ref: https://goo.gl/ftVFm9 DOI: https://doi.org/10.1016/j.bbrc.2017.05.066
Wen SY, Velmurugan BK, Day CH, Shen CY, Chun LC, et al. High density lipoprotein (HDL) reverses palmitic acid induced energy metabolism imbalance by switching CD36 and GLUT4 signaling pathways in cardiomyocyte. J Cell Physiol. 2017; 3020-3029. Ref: https://goo.gl/oph6mt DOI: https://doi.org/10.1002/jcp.26007
Park SY, Cho YR, Kim HJ, Higashimori T, Danton C, et al. Unraveling the temporal pattern of diet-induced insulin resistance in individual organs and cardiac dysfunction in C57BL/6 mice. Diabetes. 2005; 3530-3540. Ref: https://goo.gl/LtGceU DOI: https://doi.org/10.2337/diabetes.54.12.3530
Iozzo P, Chareonthaitawee P, Dutka D, Betteridge DJ, Ferrannini E, et al. Independent association of type 2 diabetes and coronary artery disease with myocardial insulin resistance. Diabetes. 2002; 3020-3024. Ref: https://goo.gl/nEBTVo DOI: https://doi.org/10.2337/diabetes.51.10.3020
Mazumder PK, O'Neill BT, Roberts MW, Buchanan J, Yun UJ, et al. Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts. Diabetes. 2004; 2366-2374. Ref: https://goo.gl/oeS4W2 DOI: https://doi.org/10.2337/diabetes.53.9.2366
How OJ, Aasum E, Severson DL, Chan WY, Essop MF, et al. Increased myocardial oxygen consumption reduces cardiac efficiency in diabetic mice. Diabetes. 2006; 466-473. Ref: https://goo.gl/2mXJ4A DOI: https://doi.org/10.2337/diabetes.55.02.06.db05-1164
Belke DD, Larsen TS, Gibbs EM, Severson DL. Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic (db/db) mice. Am J Physiol Endocrinol Metab. 2000; 1104-1113. Ref: https://goo.gl/DkGsHp DOI: https://doi.org/10.1152/ajpendo.2000.279.5.E1104
Kolter T, Uphues I,Eckel J. Molecular analysis of insulin resistance in isolated ventricular cardiomyocytes of obese Zucker rats. Am J Physiol. 1997; 59-67. Ref: https://goo.gl/GcveR7 DOI: https://doi.org/10.1152/ajpendo.1997.273.1.E59
Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science, 2004; 457-461. Ref: https://goo.gl/bRDo8T DOI: https://doi.org/10.1126/science.1103160
Wu W, Muchir A, Shan J, Bonne G,Worman HJ. Mitogen-activated protein kinase inhibitors improve heart function and prevent fibrosis in cardiomyopathy caused by mutation in lamin A/C gene. Circulation. 2011; 53-61. Ref: https://goo.gl/Qa4PS9 DOI: https://doi.org/10.1161/CIRCULATIONAHA.110.970673
Turdi S, Kandadi MR, Zhao J, Huff AF, Du M, et al. Deficiency in AMP-activated protein kinase exaggerates high fat diet-induced cardiac hypertrophy and contractile dysfunction. J Mol Cell Cardiol. 2011; 712-722. Ref: https://goo.gl/ijV3gp DOI: https://doi.org/10.1016/j.yjmcc.2010.12.007
Li YJ, Wang PH, Chen C, Zou MH,Wang DW. Improvement of mechanical heart function by trimetazidine in db/db mice. Acta Pharmacol Sin. 2010; 560-569. Ref: https://goo.gl/RV6C6P DOI: https://doi.org/10.1038/aps.2010.31
Tan SH, Shui G, Zhou J, Li JJ, Bay BH, et al. Induction of autophagy by palmitic acid via protein kinase C-mediated signaling pathway independent of mTOR (mammalian target of rapamycin). J Biol Chem. 2012; 14364-14376. Ref: https://goo.gl/MBkRby DOI: https://doi.org/10.1074/jbc.M111.294157
Marsh SA, Powell PC, Dell'italia LJ,Chatham JC. Cardiac O-GlcNAcylation blunts autophagic signaling in the diabetic heart. Life Sci. 2013; 648-656. Ref: https://goo.gl/JkXCdK DOI: https://doi.org/10.1016/j.lfs.2012.06.011
Khan MJ, Rizwan Alam M, Waldeck-Weiermair M, Karsten F, Groschner L, et al. Inhibition of autophagy rescues palmitic acid-induced necroptosis of endothelial cells. J Biol Chem. 2012; 21110-21120. Ref: https://goo.gl/jBfij3 DOI: https://doi.org/10.1074/jbc.M111.319129
Zhang QJ, Holland WL, Wilson L, Tanner JM, Kearns D, et al. Ceramide mediates vascular dysfunction in diet-induced obesity by PP2A-mediated dephosphorylation of the eNOS-Akt complex. Diabetes. 2012; 1848-1859. Ref: https://goo.gl/2K6CYx DOI: https://doi.org/10.2337/db11-1399
Ussher JR, Folmes CD, Keung W, Fillmore N, Jaswal JS, et al. Inhibition of serine palmitoyl transferase I reduces cardiac ceramide levels and increases glycolysis rates following diet-induced insulin resistance. PLoS One. 2012; e37703. Ref: https://goo.gl/HeE3o4 DOI: https://doi.org/10.1371/journal.pone.0037703
Rame JE, Barouch LA, Sack MN, Lynn EG, Abu-Asab M, et al. Caloric restriction in leptin deficiency does not correct myocardial steatosis: failure to normalize PPAR{alpha}/PGC1{alpha} and thermogenic glycerolipid/fatty acid cycling. Physiol Genomics. 2011; 726-738. Ref: https://goo.gl/c9ZM47 DOI: https://doi.org/10.1152/physiolgenomics.00088.2010
Gordon GB. Saturated free fatty acid toxicity. II. Lipid accumulation, ultrastructural alterations, and toxicity in mammalian cells in culture. Exp Mol Pathol. 1977; 262-276. Ref: https://goo.gl/dj9TM7 DOI: https://doi.org/10.1016/0014-4800(77)90035-1
Greenberg AS, Coleman RA, Kraemer FB, McManaman JL, Obin MS, et al. The role of lipid droplets in metabolic disease in rodents and humans. J Clin Invest. 2011; 2102-2110. Ref: https://goo.gl/res3cF DOI: https://doi.org/10.1172/JCI46069
Wang H, Sreenivasan U, Hu H, Saladino A, Polster BM, et al. Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic linkage to mitochondria. J Lipid Res. 2011; 2159-2168. Ref: https://goo.gl/ZfCy7H DOI: https://doi.org/10.1194/jlr.M017939
Kuramoto K, Okamura T, Yamaguchi T, Nakamura TY, Wakabayashi S, et al. Perilipin 5, a lipid droplet-binding protein, protects heart from oxidative burden by sequestering fatty acid from excessive oxidation. J Biol Chem. 2012; 23852-23863. Ref: https://goo.gl/6QDxYr DOI: https://doi.org/10.1074/jbc.M111.328708
Jordan SD, Kruger M, Willmes DM, Redemann N, Wunderlich FT, et al. Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism. Nat Cell Biol. 2011; 434-446. Ref: https://goo.gl/W5wpR7 DOI: https://doi.org/10.1038/ncb2211
Jheng HF, Tsai PJ, Guo SM, Kuo LH, Chang CS, et al. Mitochondrial fission contributes to mitochondrial dysfunction and insulin resistance in skeletal muscle. Mol Cell Biol. 2012; 309-319. Ref: https://goo.gl/LyUoeT DOI: https://doi.org/10.1128/MCB.05603-11