Lipotoxicity and cardiac dysfunction in mammals and Drosophila

References

• Arking DE, Atzmon G, Arking A, Barzilai N, Dietz HC. 2005. Association between a functional variant of the KLOTHO gene and high-density lipoprotein cholesterol, blood pressure, stroke, and longevity. Circ Res 96:412–418.
   PubMed Web of Science ®Google Scholar
• Baker KD, Thummel CS. 2007. Diabetic larvae and obese flies-emerging studies of metabolism in Drosophila. Cell Metab 6:257–266.
   PubMed Web of Science ®Google Scholar
• Birse RT, Choi J, Reardon K, Rodriguez J, Graham S, Diop S, Ocorr K, Bodmer R, Oldham S. 2010. High-fat-diet-induced obesity and heart dysfunction are regulated by the TOR pathway in Drosophila. Cell Metab 12:533–544.
   PubMed Web of Science ®Google Scholar
• Bodmer R, Venkatesh TV. 1998. Heart development in Drosophila and vertebrates: conservation of molecular mechanisms. Dev Genet 22:181–186.
   PubMedGoogle Scholar
• Bouzakri K, Koistinen HA, Zierath JR. 2005. Molecular mechanisms of skeletal muscle insulin resistance in type 2 diabetes. Curr Diabetes Rev 1:167–174.
   Google Scholar
• Brindley DN, Kok BP, Kienesberger PC, Lehner R, Dyck JR. 2010. Shedding light on the enigma of myocardial lipotoxicity: the involvement of known and putative regulators of fatty acid storage and mobilization. Am J Physiol Endocrinol Metab 298:E897–E908.
   PubMed Web of Science ®Google Scholar
• Browning JD, Horton JD. 2004. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 114:147–152.
   PubMed Web of Science ®Google Scholar
• Chen J, Muntner P, Hamm LL, Jones DW, Batuman V, Fonseca V, Whelton PK, He J. 2004. The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med 140:167–174.
   PubMed Web of Science ®Google Scholar
• 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. 2005. Transgenic expression of fatty acid transport protein 1 in the heart causes lipotoxic cardiomyopathy. Circ Res 96:225–233.
   PubMed Web of Science ®Google Scholar
• Chiu HC, Kovacs A, Ford DA, Hsu FF, Garcia R, Herrero P, Saffitz JE, Schaffer JE. 2001. A novel mouse model of lipotoxic cardiomyopathy. J Clin Invest 107:813–822.
   PubMed Web of Science ®Google Scholar
• Chow L, From A, Seaquist E. 2010. Skeletal muscle insulin resistance: the interplay of local lipid excess and mitochondrial dysfunction. Metab Clin Exp 59:70–85.
   PubMed Web of Science ®Google Scholar
• Christoffersen C, Bollano E, Lindegaard ML, Bartels ED, Goetze JP, Andersen CB, Nielsen LB. 2003. Cardiac lipid accumulation associated with diastolic dysfunction in obese mice. Endocrinology 144:3483–3490.
   PubMed Web of Science ®Google Scholar
• Cripps RM, Olson EN. 2002. Control of cardiac development by an evolutionarily conserved transcriptional network. Dev Biol 246:14–28.
   PubMed Web of Science ®Google Scholar
• DeFronzo RA, Tripathy D. 2009. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care 32 Suppl 2:S157–S163.
   PubMedGoogle Scholar
• Denzel MS, Scimia MC, Zumstein PM, Walsh K, Ruiz-Lozano P, Ranscht B. 2010. T-cadherin is critical for adiponectin-mediated cardioprotection in mice. J Clin Invest 120:4342–4352.
   PubMed Web of Science ®Google Scholar
• Després JP. 2007. Cardiovascular disease under the influence of excess visceral fat. Crit Pathw Cardiol 6:51–59.
   PubMedGoogle Scholar
• Duncan JG, Bharadwaj KG, Fong JL, Mitra R, Sambandam N, Courtois MR, Lavine KJ, Goldberg IJ, Kelly DP. 2010. Rescue of cardiomyopathy in peroxisome proliferator-activated receptor-alpha transgenic mice by deletion of lipoprotein lipase identifies sources of cardiac lipids and peroxisome proliferator-activated receptor-alpha activators. Circulation 121:426–435.
   PubMed Web of Science ®Google Scholar
• Dyntar D, Eppenberger-Eberhardt M, Maedler K, Pruschy M, Eppenberger HM, Spinas GA, Donath MY. 2001. Glucose and palmitic acid induce degeneration of myofibrils and modulate apoptosis in rat adult cardiomyocytes. Diabetes 50:2105–2113.
   PubMed Web of Science ®Google Scholar
• Fabbrini E, Sullivan S, Klein S. 2010. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology 51:679–689.
   PubMed Web of Science ®Google Scholar
• Feldstein AE. 2010. Novel insights into the pathophysiology of nonalcoholic fatty liver disease. Semin Liver Dis 30:391–401.
   PubMed Web of Science ®Google Scholar
• Forouhi NG, Jenkinson G, Thomas EL, Mullick S, Mierisova S, Bhonsle U, McKeigue PM, Bell JD. 1999. Relation of triglyceride stores in skeletal muscle cells to central obesity and insulin sensitivity in European and South Asian men. Diabetologia 42:932–935.
   PubMed Web of Science ®Google Scholar
• Fujita M, Momose A, Ohtomo T, Nishinosono A, Tanonaka K, Toyoda H, Morikawa M, Yamada J. 2011. Upregulation of fatty acyl-CoA thioesterases in the heart and skeletal muscle of rats fed a high-fat diet. Biol Pharm Bull 34:87–91.
   PubMed Web of Science ®Google Scholar
• Glenn DJ, Wang F, Nishimoto M, Cruz MC, Uchida Y, Holleran WM, Zhang Y, Yeghiazarians Y, Gardner DG. 2011. A murine model of isolated cardiac steatosis leads to cardiomyopathy. Hypertension 57:216–222.
   PubMedGoogle Scholar
• Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. 2004. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 351:1296–1305.
   PubMed Web of Science ®Google Scholar
• Goldberg RB. 2009. Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications. J Clin Endocrinol Metab 94:3171–3182.
   PubMed Web of Science ®Google Scholar
• Górska M, Dobrzyn A, Zendzian-Piotrowska M, Górski J. 2004. Effect of streptozotocin-diabetes on the functioning of the sphingomyelin-signalling pathway in skeletal muscles of the rat. Horm Metab Res 36:14–21.
   PubMedGoogle Scholar
• Grönke S, Mildner A, Fellert S, Tennagels N, Petry S, Müller G, Jäckle H, Kühnlein RP. 2005. Brummer lipase is an evolutionary conserved fat storage regulator in Drosophila. Cell Metab 1:323–330.
   PubMed Web of Science ®Google Scholar
• Grönke S, Müller G, Hirsch J, Fellert S, Andreou A, Haase T, Jäckle H, Kühnlein RP. 2007. Dual lipolytic control of body fat storage and mobilization in Drosophila. PLoS Biol 5:e137.
   PubMedGoogle Scholar
• 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. 2006. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 312:734–737.
   PubMed Web of Science ®Google Scholar
• Hannun YA, Obeid LM. 2008. Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol 9:139–150.
   PubMed Web of Science ®Google Scholar
• Heather LC, Clarke K. 2011. Metabolism, hypoxia and the diabetic heart. J Mol Cell Cardiol 50:598–605.
   PubMed Web of Science ®Google Scholar
• Hickson-Bick DL, Buja LM, McMillin JB. 2000. Palmitate-mediated alterations in the fatty acid metabolism of rat neonatal cardiac myocytes. J Mol Cell Cardiol 32:511–519.
   Google Scholar
• Hirano K, Ikeda Y, Zaima N, Sakata Y, Matsumiya G. 2008. Triglyceride deposit cardiomyovasculopathy. N Engl J Med 359:2396–2398.
   PubMed Web of Science ®Google Scholar
• Hoy AJ, Bruce CR, Turpin SM, Morris AJ, Febbraio MA, Watt MJ. 2011. Adipose triglyceride lipase-null mice are resistant to high-fat diet-induced insulin resistance despite reduced energy expenditure and ectopic lipid accumulation. Endocrinology 152:48–58.
   PubMed Web of Science ®Google Scholar
• Hug C, Wang J, Ahmad NS, Bogan JS, Tsao TS, Lodish HF. 2004. T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc Natl Acad Sci USA 101:10308–10313.
   PubMed Web of Science ®Google Scholar
• Hulver MW, Berggren JR, Cortright RN, Dudek RW, Thompson RP, Pories WJ, MacDonald KG, Cline GW, Shulman GI, Dohm GL, Houmard JA. 2003. Skeletal muscle lipid metabolism with obesity. Am J Physiol Endocrinol Metab 284:E741–E747.
   PubMed Web of Science ®Google Scholar
• Janero DR, Burghardt B, Lopez R. 1988. Protection of cardiac membrane phospholipid against oxidative injury by calcium antagonists. Biochem Pharmacol 37:4197–4203.
   PubMed Web of Science ®Google Scholar
• Jimba S, Nakagami T, Takahashi M, Wakamatsu T, Hirota Y, Iwamoto Y, Wasada T. 2005. Prevalence of non-alcoholic fatty liver disease and its association with impaired glucose metabolism in Japanese adults. Diabet Med 22:1141–1145.
   PubMed Web of Science ®Google Scholar
• Kannel WB, Wolf PA, Castelli WP, D’Agostino RB. 1987. Fibrinogen and risk of cardiovascular disease. The Framingham Study. JAMA 258:1183–1186.
   PubMed Web of Science ®Google Scholar
• Kim SK, Rulifson EJ. 2004. Conserved mechanisms of glucose sensing and regulation by Drosophila corpora cardiaca cells. Nature 431:316–320.
   PubMed Web of Science ®Google Scholar
• Kotronen A, Juurinen L, Hakkarainen A, Westerbacka J, Cornér A, Bergholm R, Yki-Järvinen H. 2008. Liver fat is increased in type 2 diabetic patients and underestimated by serum alanine aminotransferase compared with equally obese nondiabetic subjects. Diabetes Care 31:165–169.
   PubMed Web of Science ®Google Scholar
• Laplante M, Sabatini DM. 2009. An emerging role of mTOR in lipid biosynthesis. Curr Biol 19:R1046–R1052.
   PubMed Web of Science ®Google Scholar
• Laplante M, Sabatini DM. 2010. mTORC1 activates SREBP-1c and uncouples lipogenesis from gluconeogenesis. Proc Natl Acad Sci USA 107:3281–3282.
   Google Scholar
• Li LO, Klett EL, Coleman RA. 2010. Acyl-CoA synthesis, lipid metabolism and lipotoxicity. Biochim Biophys Acta 1801:246–251.
   PubMed Web of Science ®Google Scholar
• Lim HY, Wang W, Wessells RJ, Ocorr K, Bodmer R. 2011. Phospholipid homeostasis regulates lipid metabolism and cardiac function through SREBP signaling in Drosophila. Genes Dev 25:189–200.
   PubMed Web of Science ®Google Scholar
• Liu L, Shi X, Bharadwaj KG, Ikeda S, Yamashita H, Yagyu H, Schaffer JE, Yu YH, Goldberg IJ. 2009. DGAT1 expression increases heart triglyceride content but ameliorates lipotoxicity. J Biol Chem 284:36312–36323.
   PubMed Web of Science ®Google Scholar
• Liu L, Yu S, Khan RS, Ables GP, Bharadwaj KG, Hu Y, Huggins LA, Eriksson JW, Buckett LK, Turnbull AV, Ginsberg HN, Blaner WS, Huang LS, Goldberg IJ. 2011. DGAT1 deficiency decreases PPAR expression and does not lead to lipotoxicity in cardiac and skeletal muscle. J Lipid Res 52:732–744.
   Google Scholar
• Löllmann B, Grüninger S, Stricker-Krongrad A, Chiesi M. 1997. Detection and quantification of the leptin receptor splice variants Ob-Ra, b, and, e in different mouse tissues. Biochem Biophys Res Commun 238:648–652.
   PubMed Web of Science ®Google Scholar
• Lopaschuk GD, Folmes CD, Stanley WC. 2007. Cardiac energy metabolism in obesity. Circ Res 101:335–347.
   PubMed Web of Science ®Google Scholar
• Lopaschuk GD, Ussher JR, Folmes CD, Jaswal JS, Stanley WC. 2010. Myocardial fatty acid metabolism in health and disease. Physiol Rev 90:207–258.
   PubMed Web of Science ®Google Scholar
• Mathieu P, Pibarot P, Larose E, Poirier P, Marette A, Després JP. 2008. Visceral obesity and the heart. Int J Biochem Cell Biol 40:821–836.
   PubMed Web of Science ®Google Scholar
• Meade TW, Mellows S, Brozovic M, Miller GJ, Chakrabarti RR, North WR, Haines AP, Stirling Y, Imeson JD, Thompson SG. 1986. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 2:533–537.
   PubMed Web of Science ®Google Scholar
• Neely GG, Kuba K, Cammarato A, Isobe K, Amann S, Zhang L, Murata M, Elmén L, Gupta V, Arora S, Sarangi R, Dan D, Fujisawa S, Usami T, Xia CP, Keene AC, Alayari NN, Yamakawa H, Elling U, Berger C, Novatchkova M, Koglgruber R, Fukuda K, Nishina H, Isobe M, Pospisilik JA, Imai Y, Pfeufer A, Hicks AA, Pramstaller PP, Subramaniam S, Kimura A, Ocorr K, Bodmer R, Penninger JM. 2010. A global in vivo Drosophila RNAi screen identifies NOT3 as a conserved regulator of heart function. Cell 141:142–153.
   PubMed Web of Science ®Google Scholar
• Ocorr K, Akasaka T, Bodmer R. 2007. Age-related cardiac disease model of Drosophila. Mech Ageing Dev 128:112–116.
   PubMed Web of Science ®Google Scholar
• Oldham S, Hafen E. 2003. Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends Cell Biol 13:79–85.
   PubMed Web of Science ®Google Scholar
• Palanker L, Tennessen JM, Lam G, Thummel CS. 2009. Drosophila HNF4 regulates lipid mobilization and beta-oxidation. Cell Metab 9:228–239.
   PubMedGoogle Scholar
• Park SY, Cho YR, Finck BN, Kim HJ, Higashimori T, Hong EG, Lee MK, Danton C, Deshmukh S, Cline GW, Wu JJ, Bennett AM, Rothermel B, Kalinowski A, Russell KS, Kim YB, Kelly DP, Kim JK. 2005. Cardiac-specific overexpression of peroxisome proliferator-activated receptor-alpha causes insulin resistance in heart and liver. Diabetes 54:2514–2524.
   PubMed Web of Science ®Google Scholar
• Perseghin G. 2010. The role of non-alcoholic fatty liver disease in cardiovascular disease. Dig Dis 28:210–213.
   PubMed Web of Science ®Google Scholar
• Peura TT, Bosman A, Stojanov T. 2007. Derivation of human embryonic stem cell lines. Theriogenology 67:32–42.
   PubMed Web of Science ®Google Scholar
• Picano E, Morales MA, del Ry S, Sicari R. 2010. Innate inflammation in myocardial perfusion and its implication for heart failure. Ann N Y Acad Sci 1207:107–115.
   PubMed Web of Science ®Google Scholar
• Phillips LK, Prins JB. 2008. The link between abdominal obesity and the metabolic syndrome. Curr Hypertens Rep 10:156–164.
   PubMed Web of Science ®Google Scholar
• Puthanveetil P, Wang Y, Zhang D, Wang F, Kim MS, Innis S, Pulinilkunnil T, Abrahani A, Rodrigues B. 2011. Cardiac triglyceride accumulation following acute lipid excess occurs through activation of a FoxO1-iNOS-CD36 pathway. Free Radic Biol Med 51:352–363.
   PubMed Web of Science ®Google Scholar
• Qian L, Liu J, Bodmer R. 2008. Heart development in Drosophila. In Bodmer R, ed. Advances in Developmental Biology: Cardiac Development. Amsterdam, Elsevier, 1–29
   Google Scholar
• Rawson RB. 2003. The SREBP pathway–insights from Insigs and insects. Nat Rev Mol Cell Biol 4:631–640.
   PubMed Web of Science ®Google Scholar
• Saltiel AR, Kahn CR. 2001. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414:799–806.
   PubMed Web of Science ®Google Scholar
• Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson PW; American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. 2003. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Hypertension 42:1050–1065.
   PubMed Web of Science ®Google Scholar
• Schiffrin EL, Lipman ML, Mann JF. 2007. Chronic kidney disease: effects on the cardiovascular system. Circulation 116:85–97.
   PubMed Web of Science ®Google Scholar
• Schrauwen-Hinderling VB, Mensink M, Hesselink MK, Sels JP, Kooi ME, Schrauwen P. 2008. The insulin-sensitizing effect of rosiglitazone in type 2 diabetes mellitus patients does not require improved in vivo muscle mitochondrial function. J Clin Endocrinol Metab 93:2917–2921.
   Google Scholar
• Sentex E, Sergiel JP, Lucien A, Grynberg A. 1997. Trimetazidine increases phospholipid turnover in ventricular myocyte. Mol Cell Biochem 175:153–162.
   PubMed Web of Science ®Google Scholar
• Sharma S, Adrogue JV, Golfman L, Uray I, Lemm J, Youker K, Noon GP, Frazier OH, Taegtmeyer H. 2004. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. FASEB J 18:1692–1700.
   PubMed Web of Science ®Google Scholar
• Stanley WC, Recchia FA. 2010. Lipotoxicity and the development of heart failure: moving from mouse to man. Cell Metab 12:555–556.
   Google Scholar
• Stec JJ, Silbershatz H, Tofler GH, Matheney TH, Sutherland P, Lipinska I, Massaro JM, Wilson PF, Muller JE, D’Agostino RB Sr. 2000. Association of fibrinogen with cardiovascular risk factors and cardiovascular disease in the Framingham Offspring Population. Circulation 102:1634–1638.
   PubMed Web of Science ®Google Scholar
• Straczkowski M, Kowalska I, Nikolajuk A, Dzienis-Straczkowska S, Kinalska I, Baranowski M, Zendzian-Piotrowska M, Brzezinska Z, Gorski J. 2004. Relationship between insulin sensitivity and sphingomyelin signaling pathway in human skeletal muscle. Diabetes 53:1215–1221.
   PubMed Web of Science ®Google Scholar
• Son NH, Yu S, Tuinei J, Arai K, Hamai H, Homma S, Shulman GI, Abel ED, Goldberg IJ. 2010. PPAR?-induced cardiolipotoxicity in mice is ameliorated by PPARa deficiency despite increases in fatty acid oxidation. J Clin Invest 120:3443–3454.
   PubMed Web of Science ®Google Scholar
• Sowers JR. 2007. Metabolic risk factors and renal disease. Kidney Int 71:719–720.
   PubMed Web of Science ®Google Scholar
• Sparagna GC, Hickson-Bick DL, Buja LM, McMillin JB. 2000. A metabolic role for mitochondria in palmitate-induced cardiac myocyte apoptosis. Am J Physiol Heart Circ Physiol 279:H2124–H2132.
   PubMed Web of Science ®Google Scholar
• Summers SA. 2006. Ceramides in insulin resistance and lipotoxicity. Prog Lipid Res 45:42–72.
   PubMed Web of Science ®Google Scholar
• Tappia PS, Singal T. 2008. Phospholipid-mediated signaling and heart disease. Subcell Biochem 49:299–324.
   PubMedGoogle Scholar
• Tatar M, Bartke A, Antebi A. 2003. The endocrine regulation of aging by insulin-like signals. Science 299:1346–1351.
   PubMed Web of Science ®Google Scholar
• Turinsky J, O’Sullivan DM, Bayly BP. 1990. 1,2-Diacylglycerol and ceramide levels in insulin-resistant tissues of the rat in vivo. J Biol Chem 265:16880–16885.
   PubMed Web of Science ®Google Scholar
• Unger RH. 2002. Lipotoxic diseases. Annu Rev Med 53:319–336.
   PubMed Web of Science ®Google Scholar
• Van Gaal LF, Mertens IL, De Block CE. 2006. Mechanisms linking obesity with cardiovascular disease. Nature 444:875–880.
   PubMed Web of Science ®Google Scholar
• van Herpen NA, Schrauwen-Hinderling VB. 2008. Lipid accumulation in non-adipose tissue and lipotoxicity. Physiol Behav 94:231–241.
   PubMed Web of Science ®Google Scholar
• Vanholder R, Massy Z, Argiles A, Spasovski G, Verbeke F, Lameire N; European Uremic Toxin Work Group. 2005. Chronic kidney disease as cause of cardiovascular morbidity and mortality. Nephrol Dial Transplant 20:1048–1056.
   PubMed Web of Science ®Google Scholar
• Vaziri ND, Norris K. 2011. Lipid disorders and their relevance to outcomes in chronic kidney disease. Blood Purif 31:189–196.
   PubMed Web of Science ®Google Scholar
• Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, Orosz L, Müller F. 2003. Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426:620.
   PubMed Web of Science ®Google Scholar
• Wang MC, Bohmann D, Jasper H. 2005. JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling. Cell 121:115–125.
   PubMed Web of Science ®Google Scholar
• Wu D, Ren Z, Pae M, Guo W, Cui X, Merrill AH, Meydani SN. 2007. Aging up-regulates expression of inflammatory mediators in mouse adipose tissue. J Immunol 179:4829–4839.
   PubMed Web of Science ®Google Scholar
• 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. 2003. Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy. J Clin Invest 111:419–426.
   PubMed Web of Science ®Google Scholar
• Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. 2003. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423:762–769.
   PubMed Web of Science ®Google Scholar
• Yki-Järvinen H. 2005. Fat in the liver and insulin resistance. Ann Med 37:347–356.
   PubMed Web of Science ®Google Scholar
• Zaffran S, Frasch M. 2002. Early signals in cardiac development. Circ Res 91:457–469.
   PubMedGoogle Scholar
• Zeidan YH, Hannun YA. 2007. Activation of acid sphingomyelinase by protein kinase Cdelta-mediated phosphorylation. J Biol Chem 282:11549–11561.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Ren J. 2011. Role of cardiac steatosis and lipotoxicity in obesity cardiomyopathy. Hypertension 57:148–150.
   PubMed Web of Science ®Google Scholar
• Zid BM, Rogers AN, Katewa SD, Vargas MA, Kolipinski MC, Lu TA, Benzer S, Kapahi P. 2009. 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila. Cell 139:149–160.
   PubMed Web of Science ®Google Scholar