Skip to main content

Advertisement

SpringerLink
Log in

Direct effects of adipokines on the heart: focus on adiponectin

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Cardiovascular disease, including heart failure, is a principal cause of death in individuals with obesity and diabetes. However, the mechanisms of obesity- and diabetes-induced heart disease are multifaceted and remain to be clearly defined. Of relevance to this review, there is currently great research and clinical interest in the endocrine effects of adipokines on the myocardium and their role in heart failure. We will discuss the potential significance of adipokines in the pathogenesis of heart failure via their ability to regulate remodeling events including metabolism, hypertrophy, fibrosis, and cell death. As an excellent example, we will first focus on adiponectin which is best known to confer numerous cardioprotective effects. However, we comprehensively discuss the existing literature that highlights it would be naive to assume that this was always the case. We also focus on lipocalin-2 which mediates pro-inflammatory and pro-apoptotic effects. It is important when studying actions of adipokines to integrate cellular and mechanistic analyses and translate these to physiologically relevant in vivo models and clinical studies. However, assimilating studies on numerous cardiac remodeling events which ultimately dictate cardiac dysfunction into a unifying conclusion is challenging. Nevertheless, there is undoubted potential for the use of adipokines as robust biomarkers and appropriate therapeutic targets in heart failure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Gaddam KK, Ventura HO, Lavie CJ (2011) Metabolic syndrome and heart failure–the risk, paradox, and treatment. Curr Hypertens Rep 13(2):142–148. doi:10.1007/s11906-011-0179-x

    Article  PubMed  CAS  Google Scholar 

  2. Mazzone T, Chait A, Plutzky J (2008) Cardiovascular disease risk in type 2 diabetes mellitus: insights from mechanistic studies. Lancet 371(9626):1800–1809. doi:10.1016/S0140-6736(08)60768-0

    Article  PubMed  CAS  Google Scholar 

  3. Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH (2006) Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 113(6):898–918. doi:10.1161/CIRCULATIONAHA.106.171016

    Article  PubMed  Google Scholar 

  4. Anker SD, von Haehling S (2011) The obesity paradox in heart failure: accepting reality and making rational decisions. Clin Pharmacol Ther 90(1):188–190. doi:10.1038/clpt.2011.72

    Article  PubMed  CAS  Google Scholar 

  5. Abel ED, Litwin SE, Sweeney G (2008) Cardiac remodeling in obesity. Physiol Rev 88(2):389–419

    Article  PubMed  CAS  Google Scholar 

  6. Boudina S, Abel ED (2010) Diabetic cardiomyopathy, causes and effects. Rev Endocr Metab Disord 11(1):31–39. doi:10.1007/s11154-010-9131-7

    Article  PubMed  Google Scholar 

  7. Smith CC, Yellon DM (2011) Adipocytokines, cardiovascular pathophysiology and myocardial protection. Pharmacol Ther 129(2):206–219. doi:10.1016/j.pharmthera.2010.09.003

    Article  PubMed  CAS  Google Scholar 

  8. Walsh K (2009) Adipokines, myokines and cardiovascular disease. Circulation 73(1):13–18

    Article  Google Scholar 

  9. Sattar N (2012) Biomarkers for diabetes prediction, pathogenesis or pharmacotherapy guidance? Past, present and future possibilities. Diabet Med J Br Diabet Assoc 29(1):5–13. doi:10.1111/j.1464-5491.2011.03480.x

    Article  CAS  Google Scholar 

  10. Yanavitski M, Givertz MM (2011) Novel biomarkers in acute heart failure. Curr Heart Fail Rep 8(3):206–211. doi:10.1007/s11897-011-0065-5

    Article  PubMed  CAS  Google Scholar 

  11. Marette A, Sweeney G (2011) Recent insights in cardiovascular complications of diabetes. Expert Rev Endocrinol Metab 6(5):689–696

    Article  Google Scholar 

  12. Abel ED, Sweeney G (2012) Modulation of the cardiovascular system by leptin. Biochimie. doi:10.1016/j.biochi.2012.03.019

  13. Sweeney G (2010) Cardiovascular effects of leptin. Nat Rev Cardiol 7(1):22–29. doi:10.1038/nrcardio.2009.224

    Article  PubMed  CAS  Google Scholar 

  14. Tycinska AM, Lisowska A, Musial WJ, Sobkowicz B (2012) Apelin in acute myocardial infarction and heart failure induced by ischemia. Clin Chim Acta Int J Clin Chem 413(3–4):406–410. doi:10.1016/j.cca.2011.11.021

    Article  CAS  Google Scholar 

  15. Bhalla V, Kalogeropoulos A, Georgiopoulou V, Butler J (2010) Serum resistin: physiology, pathophysiology and implications for heart failure. Biomarkers Med 4(3):445–452. doi:10.2217/bmm.10.17

    Article  CAS  Google Scholar 

  16. Xu A, Vanhoutte PM (2012) Adiponectin and adipocyte fatty acid binding protein in the pathogenesis of cardiovascular disease. Am J Physiol Heart Circ Physiol 302(6):H1231–H1240. doi:10.1152/ajpheart.00765.2011

    Article  PubMed  CAS  Google Scholar 

  17. Fang X, Sweeney G (2006) Mechanisms regulating energy metabolism by adiponectin in obesity and diabetes. Biochem Soc Trans 34(Pt 5):798–801

    PubMed  CAS  Google Scholar 

  18. Yamauchi T, Kadowaki T (2008) Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases. Int J Obes (Lond) 32(Suppl 7):S13–S18. doi:10.1038/ijo.2008.233

    Article  CAS  Google Scholar 

  19. Waki H, Yamauchi T, Kamon J, Kita S, Ito Y, Hada Y, Uchida S, Tsuchida A, Takekawa S, Kadowaki T (2005) Generation of globular fragment of adiponectin by leukocyte elastase secreted by monocytic cell line THP-1. Endocrinology 146(2):790–796

    Article  PubMed  CAS  Google Scholar 

  20. Wang Y, Lam KS, Chan L, Chan KW, Lam JB, Lam MC, Hoo RC, Mak WW, Cooper GJ, Xu A (2006) Post-translational modifications of the four conserved lysine residues within the collagenous domain of adiponectin are required for the formation of its high molecular weight oligomeric complex. J Biol Chem 281(24):16391–16400

    Article  PubMed  CAS  Google Scholar 

  21. Liu Y, Retnakaran R, Hanley A, Tungtrongchitr R, Shaw C, Sweeney G (2007) Total and high molecular weight but not trimeric or hexameric forms of adiponectin correlate with markers of the metabolic syndrome and liver injury in Thai subjects. J Clin Endocrinol Metab 92(11):4313–4318

    Article  PubMed  CAS  Google Scholar 

  22. Hui X, Lam KS, Vanhoutte PM, Xu A (2012) Adiponectin and cardiovascular health: an update. Br J Pharmacol 165(3):574–590. doi:10.1111/j.1476-5381.2011.01395.x

    Article  PubMed  CAS  Google Scholar 

  23. Shetty S, Kusminski CM, Scherer PE (2009) Adiponectin in health and disease: evaluation of adiponectin-targeted drug development strategies. Trends Pharmacol Sci 30(5):234–239

    Article  PubMed  CAS  Google Scholar 

  24. Matsuzawa Y (2010) Adiponectin: a key player in obesity related disorders. Curr Pharm Des 16(17):1896–1901

    Article  PubMed  CAS  Google Scholar 

  25. Ouchi N, Shibata R, Walsh K (2006) Cardioprotection by adiponectin. Trends Cardiovasc Med 16(5):141–146

    Article  PubMed  CAS  Google Scholar 

  26. Ebert T, Fasshauer M (2011) Adiponectin: sometimes good, sometimes bad? Cardiology 118(4):236–237. doi:10.1159/000329647

    Article  PubMed  Google Scholar 

  27. Fang X, Palanivel R, Cresser J, Schram K, Ganguly R, Thong FS, Tuinei J, Xu A, Abel ED, Sweeney G (2010) An APPL1-AMPK signaling axis mediates beneficial metabolic effects of adiponectin in the heart. Am J Physiol Endocrinol Metab 299(5):E721–E729. doi:10.1152/ajpendo.00086.2010

    Article  PubMed  CAS  Google Scholar 

  28. Palanivel R, Fang X, Park M, Eguchi M, Pallan S, De Girolamo S, Liu Y, Wang Y, Xu A, Sweeney G (2007) Globular and full-length forms of adiponectin mediate specific changes in glucose and fatty acid uptake and metabolism in cardiomyocytes. Cardiovasc Res 75(1):148–157

    Article  PubMed  CAS  Google Scholar 

  29. Deepa SS, Dong LQ (2009) APPL1: role in adiponectin signaling and beyond. Am J Physiol Endocrinol Metab 296(1):E22–E36. doi:10.1152/ajpendo.90731.2008

    Article  PubMed  CAS  Google Scholar 

  30. Leroith D (2012) Pathophysiology of the metabolic syndrome: implications for the cardiometabolic risks associated with type 2 diabetes. Am J Med Sci 343(1):13–16. doi:10.1097/MAJ.0b013e31823ea214

    Article  PubMed  Google Scholar 

  31. Despres JP, Cartier A, Cote M, Arsenault BJ (2008) The concept of cardiometabolic risk: bridging the fields of diabetology and cardiology. Ann Med 40(7):514–523. doi:10.1080/07853890802004959

    Article  PubMed  CAS  Google Scholar 

  32. Ding G, Qin Q, He N, Francis-David SC, Hou J, Liu J, Ricks E, Yang Q (2007) Adiponectin and its receptors are expressed in adult ventricular cardiomyocytes and upregulated by activation of peroxisome proliferator-activated receptor gamma. J Mol Cell Cardiol 43(1):73–84. doi:10.1016/j.yjmcc.2007.04.014

    Article  PubMed  CAS  Google Scholar 

  33. Pineiro R, Iglesias MJ, Gallego R, Raghay K, Eiras S, Rubio J, Dieguez C, Gualillo O, Gonzalez-Juanatey JR, Lago F (2005) Adiponectin is synthesized and secreted by human and murine cardiomyocytes. FEBS Lett 579(23):5163–5169. doi:10.1016/j.febslet.2005.07.098

    Article  PubMed  CAS  Google Scholar 

  34. Lopaschuk GD (2008) AMP-activated protein kinase control of energy metabolism in the ischemic heart. Int J Obes (Lond) 32(Suppl 4):S29–S35. doi:10.1038/ijo.2008.120

    Article  CAS  Google Scholar 

  35. Onay-Besikci A, Altarejos JY, Lopaschuk GD (2004) gAd-globular head domain of adiponectin increases fatty acid oxidation in newborn rabbit hearts. J Biol Chem 279(43):44320–44326. doi:10.1074/jbc.M400347200

    Article  PubMed  CAS  Google Scholar 

  36. Kim MS, Wang Y, Rodrigues B (2012) Lipoprotein lipase mediated fatty acid delivery and its impact in diabetic cardiomyopathy. Biochim Biophys Acta 1821(5):800–808. doi:10.1016/j.bbalip.2011.10.001

    Article  PubMed  CAS  Google Scholar 

  37. Ganguly R, Schram K, Fang X, Kim M, Rodrigues B, Thong FS, Sweeney G (2011) Adiponectin increases LPL activity via RhoA/ROCK-mediated actin remodelling in adult rat cardiomyocytes. Endocrinology 152(1):247–254. doi:10.1210/en.2010-0530

    Article  PubMed  CAS  Google Scholar 

  38. Peterson LR, Herrero P, Schechtman KB, Racette SB, Waggoner AD, Kisrieva-Ware Z, Dence C, Klein S, Marsala J, Meyer T, Gropler RJ (2004) Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation 109(18):2191–2196. doi:10.1161/01.CIR.0000127959.28627.F8

    Article  PubMed  Google Scholar 

  39. Liao Y, Takashima S, Maeda N, Ouchi N, Komamura K, Shimomura I, Hori M, Matsuzawa Y, Funahashi T, Kitakaze M (2005) Exacerbation of heart failure in adiponectin-deficient mice due to impaired regulation of AMPK and glucose metabolism. Cardiovasc Res 67(4):705–713

    Article  PubMed  CAS  Google Scholar 

  40. O’Shea KM, Chess DJ, Khairallah RJ, Rastogi S, Hecker PA, Sabbah HN, Walsh K, Stanley WC (2010) Effects of adiponectin deficiency on structural and metabolic remodeling in mice subjected to pressure overload. Am J Physiol Heart Circ Physiol 298(6):H1639–H1645. doi:10.1152/ajpheart.00957.2009

    Article  PubMed  CAS  Google Scholar 

  41. Aerts JM, Ottenhoff R, Powlson AS, Grefhorst A, van Eijk M, Dubbelhuis PF, Aten J, Kuipers F, Serlie MJ, Wennekes T, Sethi JK, O’Rahilly S, Overkleeft HS (2007) Pharmacological inhibition of glucosylceramide synthase enhances insulin sensitivity. Diabetes 56(5):1341–1349

    Article  PubMed  CAS  Google Scholar 

  42. Holland WL, Brozinick JT, Wang LP, Hawkins ED, Sargent KM, Liu Y, Narra K, Hoehn KL, Knotts TA, Siesky A, Nelson DH, Karathanasis SK, Fontenot GK, Birnbaum MJ, Summers SA (2007) Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab 5(3):167–179

    Article  PubMed  CAS  Google Scholar 

  43. Cheng KK, Lam KS, Wu D, Wang Y, Sweeney G, Hoo RL, Zhang J, Xu A (2012) APPL1 potentiates insulin secretion in pancreatic beta cells by enhancing protein kinase Akt-dependent expression of SNARE proteins in mice. Proc Natl Acad Sci USA 109(23):8919–24. doi:10.1073/pnas.1202435109

    Google Scholar 

  44. Wang Y, Cheng KK, Lam KS, Wu D, Wang Y, Huang Y, Vanhoutte PM, Sweeney G, Li Y, Xu A (2011) APPL1 counteracts obesity-induced vascular insulin resistance and endothelial dysfunction by modulating the endothelial production of nitric oxide and endothelin-1 in mice. Diabetes 60(11):3044–3054. doi:10.2337/db11-0666

    Article  PubMed  CAS  Google Scholar 

  45. Bernardo BC, Weeks KL, Pretorius L, McMullen JR (2010) Molecular distinction between physiological and pathological cardiac hypertrophy: experimental findings and therapeutic strategies. Pharmacol Ther 128(1):191–227. doi:10.1016/j.pharmthera.2010.04.005

    Article  PubMed  CAS  Google Scholar 

  46. Wang C, Li L, Zhang ZG, Fan D, Zhu Y, Wu LL (2010) Globular adiponectin inhibits angiotensin II-induced nuclear factor kappaB activation through AMP-activated protein kinase in cardiac hypertrophy. J Cell Physiol 222(1):149–155. doi:10.1002/jcp.21931

    Article  PubMed  CAS  Google Scholar 

  47. Amin RH, Mathews ST, Alli A, Leff T (2010) Endogenously produced adiponectin protects cardiomyocytes from hypertrophy by a PPARgamma-dependent autocrine mechanism. Am J Physiol Heart Circ Physiol 299(3):H690–H698. doi:10.1152/ajpheart.01032.2009

    Article  PubMed  CAS  Google Scholar 

  48. Essick EE, Ouchi N, Wilson RM, Ohashi K, Ghobrial J, Shibata R, Pimentel DR, Sam F (2011) Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte remodeling. Am J Physiol Heart Circ Physiol 301(3):H984–H993. doi:10.1152/ajpheart.00428.2011

    Article  PubMed  CAS  Google Scholar 

  49. Shimano M, Ouchi N, Shibata R, Ohashi K, Pimentel DR, Murohara T, Walsh K (2010) Adiponectin deficiency exacerbates cardiac dysfunction following pressure overload through disruption of an AMPK-dependent angiogenic response. J Mol Cell Cardiol 49(2):210–220. doi:10.1016/j.yjmcc.2010.02.021

    Article  PubMed  CAS  Google Scholar 

  50. Shibata R, Izumiya Y, Sato K, Papanicolaou K, Kihara S, Colucci WS, Sam F, Ouchi N, Walsh K (2007) Adiponectin protects against the development of systolic dysfunction following myocardial infarction. J Mol Cell Cardiol 42(6):1065–1074

    Article  PubMed  CAS  Google Scholar 

  51. Shibata R, Ouchi N, Ito M, Kihara S, Shiojima I, Pimentel DR, Kumada M, Sato K, Schiekofer S, Ohashi K, Funahashi T, Colucci WS, Walsh K (2004) Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med 10(12):1384–1389

    Article  PubMed  CAS  Google Scholar 

  52. Hecker PA, O’Shea KM, Galvao TF, Brown BH, Stanley WC (2011) Role of adiponectin in the development of high fat diet-induced metabolic abnormalities in mice. Horm Metab Res 43(2):100–105. doi:10.1055/s-0030-1269898

    Article  PubMed  CAS  Google Scholar 

  53. 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(12):4342–4352. doi:10.1172/JCI43464

    Article  PubMed  CAS  Google Scholar 

  54. Fujita K, Maeda N, Sonoda M, Ohashi K, Hibuse T, Nishizawa H, Nishida M, Hiuge A, Kurata A, Kihara S, Shimomura I, Funahashi T (2008) Adiponectin protects against angiotensin II-induced cardiac fibrosis through activation of PPAR-alpha. Arterioscler Thromb Vasc Biol 28(5):863–870

    Article  PubMed  CAS  Google Scholar 

  55. Kassiotis C, Ballal K, Wellnitz K, Vela D, Gong M, Salazar R, Frazier OH, Taegtmeyer H (2009) Markers of autophagy are downregulated in failing human heart after mechanical unloading. Circulation 120(11 Suppl):S191–S197. doi:10.1161/CIRCULATIONAHA.108.842252

    Article  PubMed  CAS  Google Scholar 

  56. Chandrashekhar Y (2005) Role of apoptosis in ventricular remodeling. Curr Heart Fail Rep 2(1):18–22

    Article  PubMed  CAS  Google Scholar 

  57. Chiong M, Wang ZV, Pedrozo Z, Cao DJ, Troncoso R, Ibacache M, Criollo A, Nemchenko A, Hill JA, Lavandero S (2011) Cardiomyocyte death: mechanisms and translational implications. Cell Death Dis 2:e244. doi:10.1038/cddis.2011.130

    Article  PubMed  CAS  Google Scholar 

  58. Baines CP (2011) How and when do myocytes die during ischemia and reperfusion: the late phase. J Cardiovasc Pharmacol Ther 16(3–4):239–243. doi:10.1177/1074248411407769

    Article  PubMed  CAS  Google Scholar 

  59. Trivedi PS, Barouch LA (2008) Cardiomyocyte apoptosis in animal models of obesity. Curr Hypertens Rep 10(6):454–460

    Article  PubMed  CAS  Google Scholar 

  60. Yarbrough WM, Mukherjee R, Escobar GP, Sample JA, McLean JE, Dowdy KB, Hendrick JW, Gibson WC, Hardin AE, Mingoia JT, White PC, Stiko A, Armstrong RC, Crawford FA, Spinale FG (2003) Pharmacologic inhibition of intracellular caspases after myocardial infarction attenuates left ventricular remodeling: a potentially novel pathway. J Thorac Cardiovasc Surg 126(6):1892–1899

    Article  PubMed  CAS  Google Scholar 

  61. Neviere R, Hassoun SM, Decoster B, Bouazza Y, Montaigne D, Marechal X, Marciniak C, Marchetti P, Lancel S (2010) Caspase-dependent protein phosphatase 2A activation contributes to endotoxin-induced cardiomyocyte contractile dysfunction. Crit Care Med 38(10):2031–2036. doi:10.1097/CCM.0b013e3181eedafb

    PubMed  CAS  Google Scholar 

  62. Zitvogel L, Kepp O, Galluzzi L, Kroemer G (2012) Inflammasomes in carcinogenesis and anticancer immune responses. Nat Immunol 13(4):343–351. doi:10.1038/ni.2224

    Article  PubMed  CAS  Google Scholar 

  63. Park M, Youn B, Zheng XL, Wu D, Xu A, Sweeney G (2011) Globular adiponectin, acting via AdipoR1/APPL1, protects H9c2 cells from hypoxia/reoxygenation-induced apoptosis. PLoS ONE 6(4):e19143. doi:10.1371/journal.pone.0019143

    Article  PubMed  CAS  Google Scholar 

  64. Tao L, Gao E, Jiao X, Yuan Y, Li S, Christopher TA, Lopez BL, Koch W, Chan L, Goldstein BJ, Ma XL (2007) Adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress. Circulation 115(11):1408–1416

    Article  PubMed  CAS  Google Scholar 

  65. Yi W, Sun Y, Gao E, Wei X, Lau WB, Zheng Q, Wang Y, Yuan Y, Wang X, Tao L, Li R, Koch W, Ma XL (2011) Reduced cardioprotective action of adiponectin in high-fat diet-induced type II diabetic mice and its underlying mechanisms. Antioxid Redox Signal 15(7):1779–1788. doi:10.1089/ars.2010.3722

    Article  PubMed  CAS  Google Scholar 

  66. Holland WL, Miller RA, Wang ZV, Sun K, Barth BM, Bui HH, Davis KE, Bikman BT, Halberg N, Rutkowski JM, Wade MR, Tenorio VM, Kuo MS, Brozinick JT, Zhang BB, Birnbaum MJ, Summers SA, Scherer PE (2011) Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat Med 17(1):55–63. doi:10.1038/nm.2277

    Article  PubMed  CAS  Google Scholar 

  67. Konishi M, Haraguchi G, Ohigashi H, Ishihara T, Saito K, Nakano Y, Isobe M (2011) Adiponectin protects against doxorubicin-induced cardiomyopathy by anti-apoptotic effects through AMPK up-regulation. Cardiovasc Res 89(2):309–319. doi:10.1093/cvr/cvq335

    Article  PubMed  CAS  Google Scholar 

  68. Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, Funahashi T, Ouchi N, Walsh K (2005) Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med 11(10):1096–1103

    Article  PubMed  CAS  Google Scholar 

  69. Kondo K, Shibata R, Unno K, Shimano M, Ishii M, Kito T, Shintani S, Walsh K, Ouchi N, Murohara T (2010) Impact of a single intracoronary administration of adiponectin on myocardial ischemia/reperfusion injury in a pig model. Circ Cardiovasc Interv 3(2):166–173. doi:10.1161/CIRCINTERVENTIONS.109.872044

    Article  PubMed  CAS  Google Scholar 

  70. Yang Z, Klionsky DJ (2010) Eaten alive: a history of macroautophagy. Nat Cell Biol 12(9):814–822. doi:10.1038/ncb0910-814

    Article  PubMed  CAS  Google Scholar 

  71. Chen Y, Klionsky DJ (2011) The regulation of autophagy—unanswered questions. J Cell Sci 124(Pt 2):161–170. doi:10.1242/jcs.064576

    Article  PubMed  CAS  Google Scholar 

  72. Dutta D, Calvani R, Bernabei R, Leeuwenburgh C, Marzetti E (2012) Contribution of impaired mitochondrial autophagy to cardiac aging: mechanisms and therapeutic opportunities. Circ Res 110(8):1125–1138. doi:10.1161/CIRCRESAHA.111.246108

    Article  PubMed  CAS  Google Scholar 

  73. Xie M, Morales CR, Lavandero S, Hill JA (2011) Tuning flux: autophagy as a target of heart disease therapy. Curr Opin Cardiol 26(3):216–222. doi:10.1097/HCO.0b013e328345980a

    Article  PubMed  CAS  Google Scholar 

  74. Mellor KM, Reichelt ME, Delbridge LM (2011) Autophagy anomalies in the diabetic myocardium. Autophagy 7(10):1263–1267. doi:10.4161/auto.7.10.17148

    Article  PubMed  CAS  Google Scholar 

  75. Dong Y, Undyala VV, Gottlieb RA, Mentzer RM Jr, Przyklenk K (2010) Autophagy: definition, molecular machinery, and potential role in myocardial ischemia-reperfusion injury. J Cardiovasc Pharmacol Ther 15(3):220–230. doi:10.1177/1074248410370327

    Article  PubMed  CAS  Google Scholar 

  76. Cao DJ, Gillette TG, Hill JA (2009) Cardiomyocyte autophagy: remodeling, repairing, and reconstructing the heart. Curr Hypertens Rep 11(6):406–411

    Article  PubMed  Google Scholar 

  77. Zhu H, Tannous P, Johnstone JL, Kong Y, Shelton JM, Richardson JA, Le V, Levine B, Rothermel BA, Hill JA (2007) Cardiac autophagy is a maladaptive response to hemodynamic stress. J Clin Invest 117(7):1782–1793. doi:10.1172/JCI27523

    Article  PubMed  CAS  Google Scholar 

  78. Troncoso R, Vicencio JM, Parra V, Nemchenko A, Kawashima Y, Del Campo A, Toro B, Battiprolu PK, Aranguiz P, Chiong M, Yakar S, Gillette TG, Hill JA, Abel ED, Leroith D, Lavandero S (2012) Energy-preserving effects of IGF-1 antagonize starvation-induced cardiac autophagy. Cardiovasc Res 93(2):320–329. doi:10.1093/cvr/cvr321

    Article  PubMed  CAS  Google Scholar 

  79. Sugimoto S, Shiomi K, Yamamoto A, Nishino I, Nonaka I, Ohi T (2007) LAMP-2 positive vacuolar myopathy with dilated cardiomyopathy. Intern Med 46(11):757–760

    Article  PubMed  Google Scholar 

  80. Mihaylova MM, Shaw RJ (2011) The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat Cell Biol 13(9):1016–1023. doi:10.1038/ncb2329

    Article  PubMed  CAS  Google Scholar 

  81. Habeeb BS, Kitayama J, Nagawa H (2011) Adiponectin supports cell survival in glucose deprivation through enhancement of autophagic response in colorectal cancer cells. Cancer Sci 102(5):999–1006. doi:10.1111/j.1349-7006.2011.01902.x

    Article  PubMed  CAS  Google Scholar 

  82. He C, Bassik MC, Moresi V, Sun K, Wei Y, Zou Z, An Z, Loh J, Fisher J, Sun Q, Korsmeyer S, Packer M, May HI, Hill JA, Virgin HW, Gilpin C, Xiao G, Bassel-Duby R, Scherer PE, Levine B (2012) Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature 481(7382):511–515. doi:10.1038/nature10758

    Article  PubMed  CAS  Google Scholar 

  83. Aviv Y, Shaw J, Gang H, Kirshenbaum LA (2011) Regulation of autophagy in the heart: “you only live twice”. Antioxid Redox Signal 14(11):2245–2250. doi:10.1089/ars.2010.3479

    Article  PubMed  CAS  Google Scholar 

  84. Gurusamy N, Das DK (2009) Is autophagy a double-edged sword for the heart? Acta Physiol Hung 96(3):267–276. doi:10.1556/APhysiol.96.2009.3.2

    Article  PubMed  CAS  Google Scholar 

  85. Fomovsky GM, Thomopoulos S, Holmes JW (2010) Contribution of extracellular matrix to the mechanical properties of the heart. J Mol Cell Cardiol 48(3):490–496. doi:10.1016/j.yjmcc.2009.08.003

    Article  PubMed  CAS  Google Scholar 

  86. Hutchinson KR, Stewart JA Jr, Lucchesi PA (2010) Extracellular matrix remodeling during the progression of volume overload-induced heart failure. J Mol Cell Cardiol 48(3):564–569. doi:10.1016/j.yjmcc.2009.06.001

    Article  PubMed  CAS  Google Scholar 

  87. Schram K, Sweeney G (2008) Implications of myocardial matrix remodeling by adipokines in obesity-related heart failure. Trends Cardiovasc Med 18(6):199–205. doi:10.1016/j.tcm.2008.10.001

    Article  PubMed  CAS  Google Scholar 

  88. Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB (2004) Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 291(14):1730–1737

    Article  PubMed  CAS  Google Scholar 

  89. Frystyk J, Berne C, Berglund L, Jensevik K, Flyvbjerg A, Zethelius B (2007) Serum adiponectin is a predictor of coronary heart disease: a population-based 10-year follow-up study in elderly men. J Clin Endocrinol Metab 92(2):571–576

    Article  PubMed  CAS  Google Scholar 

  90. Koenig W, Khuseyinova N, Baumert J, Meisinger C, Lowel H (2006) Serum concentrations of adiponectin and risk of type 2 diabetes mellitus and coronary heart disease in apparently healthy middle-aged men: results from the 18-year follow-up of a large cohort from southern Germany. J Am Coll Cardiol 48(7):1369–1377

    Article  PubMed  CAS  Google Scholar 

  91. Schulze MB, Shai I, Rimm EB, Li T, Rifai N, Hu FB (2005) Adiponectin and future coronary heart disease events among men with type 2 diabetes. Diabetes 54(2):534–539

    Article  PubMed  CAS  Google Scholar 

  92. Laughlin GA, Barrett-Connor E, May S, Langenberg C (2007) Association of adiponectin with coronary heart disease and mortality: the Rancho Bernardo study. Am J Epidemiol 165(2):164–174

    Article  PubMed  Google Scholar 

  93. Kawano T, Saito T, Yasu T, Nakamura T, Namai K, Tamemoto H, Kawakami M, Saito M, Ishikawa SE (2005) Close association of hypoadiponectinemia with arteriosclerosis obliterans and ischemic heart disease. Metabolism 54(5):653–656

    Article  PubMed  CAS  Google Scholar 

  94. Hong SJ, Park CG, Seo HS, Oh DJ, Ro YM (2004) Associations among plasma adiponectin, hypertension, left ventricular diastolic function and left ventricular mass index. Blood Press 13(4):236–242

    Article  PubMed  CAS  Google Scholar 

  95. Chen WJ, Rijzewijk LJ, van der Meer RW, Heymans MW, van Duinkerken E, Lubberink M, Lammertsma AA, Lamb HJ, de Roos A, Romijn JA, Smit JW, Bax JJ, Bjerre M, Frystyk J, Flyvbjerg A, Diamant M (2011) Association of plasma osteoprotegerin and adiponectin with arterial function, cardiac function and metabolism in asymptomatic type 2 diabetic men. Cardiovasc Diabetol 10:67. doi:10.1186/1475-2840-10-67

    Article  PubMed  Google Scholar 

  96. Bidulescu A, Liu J, Musani SK, Fox ER, Samdarshi TE, Sarpong DF, Vaccarino V, Wilson PW, Arnett DK, Din-Dzietham R, Taylor HA, Gibbons GH (2011) Association of adiponectin with left ventricular mass in blacks: the Jackson Heart Study. Circ Heart Fail 4(6):747–753. doi:10.1161/CIRCHEARTFAILURE.110.959742

    Article  PubMed  CAS  Google Scholar 

  97. Unno K, Shibata R, Izawa H, Hirashiki A, Murase Y, Yamada T, Kobayashi M, Noda A, Nagata K, Ouchi N, Murohara T (2010) Adiponectin acts as a positive indicator of left ventricular diastolic dysfunction in patients with hypertrophic cardiomyopathy. Heart 96(5):357–361. doi:10.1136/hrt.2009.172320

    Article  PubMed  Google Scholar 

  98. Kanaya AM, Wassel Fyr C, Vittinghoff E, Havel PJ, Cesari M, Nicklas B, Harris T, Newman AB, Satterfield S, Cummings SR (2006) Serum adiponectin and coronary heart disease risk in older Black and White Americans. J Clin Endocrinol Metab 91(12):5044–5050

    Article  PubMed  CAS  Google Scholar 

  99. George J, Patal S, Wexler D, Sharabi Y, Peleg E, Kamari Y, Grossman E, Sheps D, Keren G, Roth A (2006) Circulating adiponectin concentrations in patients with congestive heart failure. Heart 92(10):1420–1424

    Article  PubMed  CAS  Google Scholar 

  100. Cavusoglu E, Chopra V, Battala V, Ruwende C, Yanamadala S, Eng C, Pinsky DJ, Marmur JD (2008) Baseline plasma adiponectin levels as a predictor of left ventricular systolic dysfunction in patients referred for coronary angiography. Am J Cardiol 101(8):1073–1078. doi:10.1016/j.amjcard.2007.12.008

    Article  PubMed  CAS  Google Scholar 

  101. McEntegart MB, Awede B, Petrie MC, Sattar N, Dunn FG, MacFarlane NG, McMurray JJ (2007) Increase in serum adiponectin concentration in patients with heart failure and cachexia: relationship with leptin, other cytokines, and B-type natriuretic peptide. Eur Heart J 28(7):829–835. doi:10.1093/eurheartj/ehm033

    Article  PubMed  CAS  Google Scholar 

  102. Kistorp C, Faber J, Galatius S, Gustafsson F, Frystyk J, Flyvbjerg A, Hildebrandt P (2005) Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure. Circulation 112(12):1756–1762. doi:10.1161/CIRCULATIONAHA.104.530972

    Article  PubMed  CAS  Google Scholar 

  103. Nakamura T, Funayama H, Kubo N, Yasu T, Kawakami M, Saito M, Momomura S, Ishikawa SE (2006) Association of hyperadiponectinemia with severity of ventricular dysfunction in congestive heart failure. Circulation 70(12):1557–1562

    Article  Google Scholar 

  104. Beatty AL, Zhang MH, Ku IA, Na B, Schiller NB, Whooley MA (2012) Adiponectin is associated with increased mortality and heart failure in patients with stable ischemic heart disease: Data from the Heart and Soul Study. Atherosclerosis 220(2):587–92. doi:10.1016/j.atherosclerosis.2011.11.038

    Google Scholar 

  105. Kozakova M, Muscelli E, Flyvbjerg A, Frystyk J, Morizzo C, Palombo C, Ferrannini E (2008) Adiponectin and left ventricular structure and function in healthy adults. J Clin Endocrinol Metab 93(7):2811–2818. doi:10.1210/jc.2007-2580

    Article  PubMed  CAS  Google Scholar 

  106. Gustafsson S, Lind L, Zethelius B, Venge P, Flyvbjerg A, Soderberg S, Ingelsson E (2010) Adiponectin and cardiac geometry and function in elderly: results from two community-based cohort studies. Eur J Endocrinol 162(3):543–550. doi:10.1530/EJE-09-1006

    Article  PubMed  CAS  Google Scholar 

  107. Xu A, Chan KW, Hoo RL, Wang Y, Tan KC, Zhang J, Chen B, Lam MC, Tse C, Cooper GJ, Lam KS (2005) Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes. J Biol Chem 280(18):18073–18080. doi:10.1074/jbc.M414231200

    Article  PubMed  CAS  Google Scholar 

  108. Arai Y, Takayama M, Abe Y, Hirose N (2011) Adipokines and aging. J Atheroscler Thromb 18(7):545–550

    Article  PubMed  CAS  Google Scholar 

  109. Kadowaki T, Yamauchi T, Kubota N (2008) The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS. FEBS Lett 582(1):74–80. doi:10.1016/j.febslet.2007.11.070

    Article  PubMed  CAS  Google Scholar 

  110. Dadson K, Liu Y, Sweeney G (2011) Adiponectin action: a combination of endocrine and autocrine/paracrine effects. Front Cell Endocrinol 2(62):1–14

    Google Scholar 

  111. Palanivel R, Vu V, Park M, Fang X, Sweeney G (2008) Differential impact of adipokines derived from primary adipocytes of wild-type versus streptozotocin-induced diabetic rats on glucose and fatty acid metabolism in cardiomyocytes. J Endocrinol 199(3):389–397. doi:10.1677/JOE-08-0336

    Article  PubMed  CAS  Google Scholar 

  112. Fang X, Fetros J, Dadson KE, Xu A, Sweeney G (2009) Leptin prevents the metabolic effects of adiponectin in L6 myotubes. Diabetologia 52(10):2190–2200. doi:10.1007/s00125-009-1462-0

    Article  PubMed  CAS  Google Scholar 

  113. Yoon JH, Park JK, Oh SS, Lee KH, Kim SK, Cho IJ, Kim JK, Kang HT, Ahn SG, Lee JW, Lee SH, Eom A, Kim JY, Ahn SV, Koh SB (2011) The ratio of serum leptin to adiponectin provides adjunctive information to the risk of metabolic syndrome beyond the homeostasis model assessment insulin resistance: the Korean Genomic Rural Cohort Study. Clin Chim Acta Int J Clin Chem 412(23–24):2199–2205. doi:10.1016/j.cca.2011.08.003

    Article  CAS  Google Scholar 

  114. Ebinuma H, Miida T, Yamauchi T, Hada Y, Hara K, Kubota N, Kadowaki T (2007) Improved ELISA for selective measurement of adiponectin multimers and identification of adiponectin in human cerebrospinal fluid. Clin Chem 53(8):1541–1544. doi:10.1373/clinchem.2007.085654

    Article  PubMed  CAS  Google Scholar 

  115. Lopez L (2009) Advances in echocardiography. Curr Opin Pediatr 21(5):579–584. doi:10.1097/MOP.0b013e32832ff38e

    Article  PubMed  Google Scholar 

  116. Ohara T, Hashimura K, Asakura M, Ogai A, Amaki M, Hasegawa T, Kanzaki H, Sonoda M, Nishizawa H, Funahashi T, Kitakaze M (2011) Dynamic changes in plasma total and high molecular weight adiponectin levels in acute heart failure. J Cardiol 58(2):181–190. doi:10.1016/j.jjcc.2011.06.010

    Article  PubMed  Google Scholar 

  117. Masson S, Gori F, Latini R, Milani V, Flyvbjerg A, Frystyk J, Crociati L, Pietri S, Vago T, Barlera S, Maggioni AP, Tognoni G, Tavazzi L, Omland T, Franzosi MG (2011) Adiponectin in chronic heart failure: influence of diabetes and genetic variants. Eur J Clin Invest 41(12):1330–1338. doi:10.1111/j.1365-2362.2011.02548.x

    Article  PubMed  CAS  Google Scholar 

  118. Pedersen BK, Febbraio MA (2008) Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Phys Rev 88(4):1379–1406. doi:10.1152/physrev.90100.2007

    Article  CAS  Google Scholar 

  119. Skurk C, Wittchen F, Suckau L, Witt H, Noutsias M, Fechner H, Schultheiss HP, Poller W (2008) Description of a local cardiac adiponectin system and its deregulation in dilated cardiomyopathy. Eur Heart J 29(9):1168–1180. doi:10.1093/eurheartj/ehn136

    Article  PubMed  CAS  Google Scholar 

  120. Liao Y, Xuan W, Zhao J, Bin J, Zhao H, Asakura M, Funahashi T, Takashima S, Kitakaze M (2010) Antihypertrophic effects of adiponectin on cardiomyocytes are associated with the inhibition of heparin-binding epidermal growth factor signaling. Biochem Biophys Res Commun 393(3):519–525. doi:10.1016/j.bbrc.2010.02.039

    Article  PubMed  CAS  Google Scholar 

  121. Haugen E, Furukawa Y, Isic A, Fu M (2008) Increased adiponectin level in parallel with increased NT-pro BNP in patients with severe heart failure in the elderly: a hospital cohort study. Int J Cardiol 125(2):216–219. doi:10.1016/j.ijcard.2007.12.002

    Article  PubMed  Google Scholar 

  122. Tsukamoto O, Fujita M, Kato M, Yamazaki S, Asano Y, Ogai A, Okazaki H, Asai M, Nagamachi Y, Maeda N, Shintani Y, Minamino T, Asakura M, Kishimoto I, Funahashi T, Tomoike H, Kitakaze M (2009) Natriuretic peptides enhance the production of adiponectin in human adipocytes and in patients with chronic heart failure. J Am Coll Cardiol 53(22):2070–2077. doi:10.1016/j.jacc.2009.02.038

    Article  PubMed  CAS  Google Scholar 

  123. Kintscher U (2007) Does adiponectin resistance exist in chronic heart failure? Eur Heart J 28(14):1676–1677. doi:10.1093/eurheartj/ehm233

    Article  PubMed  Google Scholar 

  124. Khan RS, Kato TS, Chokshi A, Chew M, Yu S, Wu C, Singh P, Cheema FH, Takayama H, Harris C, Reyes-Soffer G, Knoll R, Milting H, Naka Y, Mancini D, Schulze PC (2012) Adipose tissue inflammation and adiponectin resistance in patients with advanced heart failure: correction after ventricular assist device implantation. Circ Heart Fail 5(3):340–348. doi:10.1161/CIRCHEARTFAILURE.111.964031

    Article  PubMed  CAS  Google Scholar 

  125. Li R, Lau WB, Ma XL (2010) Adiponectin resistance and vascular dysfunction in the hyperlipidemic state. Acta Pharmacol Sin 31(10):1258–1266. doi:10.1038/aps.2010.95

    Article  PubMed  CAS  Google Scholar 

  126. Van Berendoncks AM, Garnier A, Beckers P, Hoymans VY, Possemiers N, Fortin D, Van Hoof V, Dewilde S, Vrints CJ, Ventura-Clapier R, Conraads VM (2011) Exercise training reverses adiponectin resistance in skeletal muscle of patients with chronic heart failure. Heart 97(17):1403–1409. doi:10.1136/hrt.2011.226373

    Article  PubMed  CAS  Google Scholar 

  127. Springer J, Anker SD, Doehner W (2010) Adiponectin resistance in heart failure and the emerging pattern of metabolic failure in chronic heart failure. Circ Heart Fail 3(2):181–182. doi:10.1161/CIRCHEARTFAILURE.110.945063

    Article  PubMed  Google Scholar 

  128. Van Berendoncks AM, Garnier A, Beckers P, Hoymans VY, Possemiers N, Fortin D, Martinet W, Van Hoof V, Vrints CJ, Ventura-Clapier R, Conraads VM (2010) Functional adiponectin resistance at the level of the skeletal muscle in mild to moderate chronic heart failure. Circ Heart Fail 3(2):185–194. doi:10.1161/CIRCHEARTFAILURE.109.885525

    Article  PubMed  CAS  Google Scholar 

  129. Lin HV, Kim JY, Pocai A, Rossetti L, Shapiro L, Scherer PE, Accili D (2007) Adiponectin resistance exacerbates insulin resistance in insulin receptor transgenic/knockout mice. Diabetes 56(8):1969–1976. doi:10.2337/db07-0127

    Article  PubMed  CAS  Google Scholar 

  130. Mullen KL, Smith AC, Junkin KA, Dyck DJ (2007) Globular adiponectin resistance develops independently of impaired insulin-stimulated glucose transport in soleus muscle from high-fat-fed rats. Am J Physiol Endocrinol Metab 293(1):E83–E90. doi:10.1152/ajpendo.00545.2006

    Article  PubMed  CAS  Google Scholar 

  131. Fang X, Palanivel R, Zhou X, Liu Y, Xu A, Wang Y, Sweeney G (2005) Hyperglycemia- and hyperinsulinemia-induced alteration of adiponectin receptor expression and adiponectin effects in L6 myoblasts. J Mol Endocrinol 35(3):465–476. doi:10.1677/jme.1.01877

    Article  PubMed  CAS  Google Scholar 

  132. Van Berendoncks AM, Conraads VM (2011) Functional adiponectin resistance and exercise intolerance in heart failure. Curr Heart Fail Rep 8(2):113–122. doi:10.1007/s11897-011-0056-6

    Article  PubMed  CAS  Google Scholar 

  133. Wang T, Qiao S, Lei S, Liu Y, Ng KF, Xu A, Lam KS, Irwin MG, Xia Z (2011) N-acetylcysteine and allopurinol synergistically enhance cardiac adiponectin content and reduce myocardial reperfusion injury in diabetic rats. PLoS ONE 6(8):e23967. doi:10.1371/journal.pone.0023967

    Article  PubMed  CAS  Google Scholar 

  134. Jang Y, Lee JH, Wang Y, Sweeney G (2012) Emerging clinical and experimental evidence for the role of lipocalin-2 in metabolic syndrome. Clin Exp Pharmacol Physiol 39(2):194–199. doi:10.1111/j.1440-1681.2011.05557.x

    Article  PubMed  CAS  Google Scholar 

  135. Wang Y, Lam KS, Kraegen EW, Sweeney G, Zhang J, Tso AW, Chow WS, Wat NM, Xu JY, Hoo RL, Xu A (2007) Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem 53(1):34–41. doi:10.1373/clinchem.2006.075614

    Article  PubMed  CAS  Google Scholar 

  136. Law IK, Xu A, Lam KS, Berger T, Mak TW, Vanhoutte PM, Liu JT, Sweeney G, Zhou M, Yang B, Wang Y (2010) Lipocalin-2 deficiency attenuates insulin resistance associated with aging and obesity. Diabetes 59(4):872–882. doi:10.2337/db09-1541

    Article  PubMed  CAS  Google Scholar 

  137. Latouche C, El Moghrabi S, Messaoudi S, Nguyen Dinh Cat A, Hernandez-Diaz I, Alvarez de la Rosa D, Perret C, Lopez Andres N, Rossignol P, Zannad F, Farman N, Jaisser F (2012) Neutrophil gelatinase-associated lipocalin is a novel mineralocorticoid target in the cardiovascular system. Hypertension 59(5):966–972. doi:10.1161/HYPERTENSIONAHA.111.187872

    Article  PubMed  CAS  Google Scholar 

  138. Ding L, Hanawa H, Ota Y, Hasegawa G, Hao K, Asami F, Watanabe R, Yoshida T, Toba K, Yoshida K, Ogura M, Kodama M, Aizawa Y (2010) Lipocalin-2/neutrophil gelatinase-B associated lipocalin is strongly induced in hearts of rats with autoimmune myocarditis and in human myocarditis. Circulation 74(3):523–530

    Article  CAS  Google Scholar 

  139. Choi KM, Lee JS, Kim EJ, Baik SH, Seo HS, Choi DS, Oh DJ, Park CG (2008) Implication of lipocalin-2 and visfatin levels in patients with coronary heart disease. Eur J Endocrinol 158(2):203–207. doi:10.1530/EJE-07-0633

    Article  PubMed  CAS  Google Scholar 

  140. Aigner F, Maier HT, Schwelberger HG, Wallnofer EA, Amberger A, Obrist P, Berger T, Mak TW, Maglione M, Margreiter R, Schneeberger S, Troppmair J (2007) Lipocalin-2 regulates the inflammatory response during ischemia and reperfusion of the transplanted heart. Am J Transplant 7(4):779–788. doi:10.1111/j.1600-6143.2006.01723.x

    Article  PubMed  CAS  Google Scholar 

  141. Yang B, Fan P, Xu A, Lam KS, Berger T, Mak TW, Tse HF, Yue JW, Song E, Vanhoutte PM, Sweeney G, Wang Y (2012) Improved functional recovery to I/R injury in hearts from lipocalin-2 deficiency mice: restoration of mitochondrial function and phospholipids remodeling. Am J Transl Res 4(1):60–71

    PubMed  CAS  Google Scholar 

  142. Xu G, Ahn J, Chang S, Eguchi M, Ogier A, Han S, Park Y, Shim C, Jang Y, Yang B, Xu A, Wang Y, Sweeney G (2012) Lipocalin-2 induces cardiomyocyte apoptosis by increasing intracellular iron accumulation. J Biol Chem 287(7):4808–4817. doi:10.1074/jbc.M111.275719

    Article  PubMed  CAS  Google Scholar 

  143. Murphy CJ, Oudit GY (2010) Iron-overload cardiomyopathy: pathophysiology, diagnosis, and treatment. J Card Fail 16(11):888–900. doi:10.1016/j.cardfail.2010.05.009

    Article  PubMed  CAS  Google Scholar 

  144. Gujja P, Rosing DR, Tripodi DJ, Shizukuda Y (2010) Iron overload cardiomyopathy: better understanding of an increasing disorder. J Am Coll Cardiol 56(13):1001–1012. doi:10.1016/j.jacc.2010.03.083

    Article  PubMed  CAS  Google Scholar 

  145. Sommer P, Sweeney G (2010) Functional and mechanistic integration of infection and the metabolic syndrome. Korean Diabetes J 34(2):71–76. doi:10.4093/kdj.2010.34.2.71

    Article  PubMed  Google Scholar 

  146. Yndestad A, Landro L, Ueland T, Dahl CP, Flo TH, Vinge LE, Espevik T, Froland SS, Husberg C, Christensen G, Dickstein K, Kjekshus J, Oie E, Gullestad L, Aukrust P (2009) Increased systemic and myocardial expression of neutrophil gelatinase-associated lipocalin in clinical and experimental heart failure. Eur Heart J 30(10):1229–1236. doi:10.1093/eurheartj/ehp088

    Article  PubMed  CAS  Google Scholar 

  147. Mann DL (2011) The emerging role of innate immunity in the heart and vascular system: for whom the cell tolls. Circ Res 108(9):1133–1145. doi:10.1161/CIRCRESAHA.110.226936

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Related work in the authors’ laboratory was funded by grants from Heart & Stroke Foundation of Canada, Canadian Diabetes Association and Canadian Institutes of Health Research (CIHR). MP received student support from The Natural Sciences and Engineering Research Council of Canada (NSERC). We thank Hanna Park (www.hannaparkdesigner.com) for assistance with figure illustrations. Finally, we attempted to include as many pertinent citations as possible and regret it was not possible to include every relevant publication.

Conflict of interest

Both Gary Sweeney & Min Park have no conflicts of interest or financial ties to disclose.

Author information

Authors and Affiliations

  1. Department of Biology, York University, Toronto, ON, M3J 1P3, Canada

    Min Park & Gary Sweeney

Authors
  1. Min Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gary Sweeney
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gary Sweeney.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Park, M., Sweeney, G. Direct effects of adipokines on the heart: focus on adiponectin. Heart Fail Rev 18, 631–644 (2013). https://doi.org/10.1007/s10741-012-9337-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-012-9337-8

Keywords

Search

Navigation