Skip to main content

Advertisement

Log in

Functional Adiponectin Resistance and Exercise Intolerance in Heart Failure

  • Published:
Current Heart Failure Reports Aims and scope Submit manuscript

Abstract

The contribution of skeletal muscle myopathy to the phenotype of patients with chronic heart failure (CHF) has become generally accepted. Besides the macro- and microscopic changes that develop during the progressive process of muscular wasting, functional abnormalities manifest in an earlier stage. Analogous to the failing heart, alterations in skeletal muscle energy metabolism, including insulin resistance, are increasingly recognized. In the search for factors causing this observed myopathy, adipokines receive growing attention. In particular, adiponectin is of special interest due to its fundamental role in skeletal muscle energy metabolism. In strong contrast with patients at risk for cardiovascular disease, circulating adiponectin levels are increased in patients with CHF, and this finding is associated with adverse outcome. Recently, the concept of functional skeletal muscle adiponectin resistance has been suggested to explain compensatory elevated adiponectin levels in CHF. Unraveling of adiponectin’s complex downstream signalling pathways and insights into the concept of adiponectin resistance hopefully will disengage the road for targeted therapeutic interventions.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Anker SD, Steinborn W, Strassburg S. Cardiac cachexia. Ann Med. 2004;36:518–29.

    Article  PubMed  Google Scholar 

  2. Clark AL, Poole-Wilson PA, Coats AJ. Exercise limitation in chronic heart failure: central role of the periphery. J Am Coll Cardiol. 1996;28:1092–102.

    Article  PubMed  CAS  Google Scholar 

  3. Conraads VM, Hoymans VY, Vrints CJ. Heart failure and cachexia: insights offered from molecular biology. Front Biosci. 2008;13:325–35.

    Article  PubMed  CAS  Google Scholar 

  4. Ventura-Clapier R, Garnier A, Veksler V. Energy metabolism in heart failure. J Physiol. 2004;555:1–13.

    Article  PubMed  CAS  Google Scholar 

  5. Doehner W, von Haehling S, Anker SD. Insulin resistance in chronic heart failure. J Am Coll Cardiol. 2008;52:239–40.

    Article  PubMed  Google Scholar 

  6. ALZadjali MA, Godfrey V, Khan F, et al. Insulin resistance is highly prelevant and is associated with reduced exercise intolerance in nondiabetic patients with heart failure. J Am Coll Cardiol. 2009;53:747–53.

    Article  PubMed  CAS  Google Scholar 

  7. Ashrafian H, Frenneaux MP, Opie LH. Metabolic mechanisms in heart failure. Circulation. 2007;116:434–48.

    Article  PubMed  CAS  Google Scholar 

  8. Karbowska J, Kochan Z. Role of adiponectin in the regulation of carbohydrate and lipid metabolism. J Physiol Pharmacol. 2006;57:103–13.

    PubMed  Google Scholar 

  9. Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem. 1995;270:26746–9.

    Article  PubMed  CAS  Google Scholar 

  10. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem. 1996;271:10697–703.

    Article  PubMed  CAS  Google Scholar 

  11. Maeda K, Okubo K, Shimomura I, et al. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem Biophys Res Commun. 1996;221:286–9.

    Article  PubMed  CAS  Google Scholar 

  12. Nakano Y, Tobe T, Choi-Miura NH, et al. Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J Biochem. 1996;120:803–12.

    PubMed  CAS  Google Scholar 

  13. Shapiro L, Scherer PE. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr Biol. 1998;8:335–8.

    Article  PubMed  CAS  Google Scholar 

  14. Ruan H, Lodish HF. Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha. Cytokine Growth Factor Rev. 2003;14:447–55.

    Article  PubMed  CAS  Google Scholar 

  15. Wang Y, Xu A, Knight C, et al. Hydroxylation and glycosylation of the four conserved lysine residues in the collagenous domain of adiponectin. Potential role in the modulation of its insulin-sensitizing activity. J Biol Chem. 2002;277:19521–9.

    Article  PubMed  CAS  Google Scholar 

  16. Wang Y, Lam KS, Chan L, et al. 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. 2006;281:16391–400.

    Article  PubMed  CAS  Google Scholar 

  17. Tsao TS, Tomas E, Murrey HE, et al. Role of disulfide bonds in Acrp30/adiponectin structure and signaling specificity. Different oligomers activate different signal transduction pathways. J Biol Chem. 2003;278:50810–7.

    Article  PubMed  CAS  Google Scholar 

  18. Pajvani UB, Du X, Combs TP, et al. Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications for metabolic regulation and bioactivity. J Biol Chem. 2003;278:9073–85.

    Article  PubMed  CAS  Google Scholar 

  19. Trujillo ME, Scherer PE. Adiponectin–journey from an adipocyte secretory protein to biomarker of the metabolic syndrome. J Intern Med. 2005;257:167–75.

    Article  PubMed  CAS  Google Scholar 

  20. Ouchi N, Kobayashi H, Kihara S, et al. Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem. 2004;279:1304–9.

    Article  PubMed  CAS  Google Scholar 

  21. Heidemann C, Sun Q, van Dam RM, et al. Total and high-molecular-weight adiponectin and resistin in relation to the risk for type 2 diabetes in women. Ann Intern Med. 2008;149:307–16.

    PubMed  Google Scholar 

  22. Bluher M, Brennan AM, Kelesidis T, et al. Total and high-molecular weight adiponectin in relation to metabolic variables at baseline and in response to an exercise treatment program: comparative evaluation of three assays. Diab Care. 2007;30:280–5.

    Article  Google Scholar 

  23. Almeda-Valdes P, Cuevas-Ramos D, Mehta R, et al. Total and high molecular weight adiponectin have similar utility for the identification of insulin resistance. Cardiovasc Diabetol. 9:26.

  24. Fruebis J, Tsao TS, Javorschi S, et al. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA. 2001;98:2005–10.

    Article  PubMed  CAS  Google Scholar 

  25. Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003;423:762–9.

    Article  PubMed  CAS  Google Scholar 

  26. Hug C, Wang J, Ahmad NS, et al. T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc Natl Acad Sci USA. 2004;101:10308–13.

    Article  PubMed  CAS  Google Scholar 

  27. Denzel MS, Scimia MC, Zumstein PM, et al. T-cadherin is critical for adiponectin-mediated cardioprotection in mice. J Clin Invest. 120:4342–52.

  28. Kadowaki T, Yamauchi T, Kubota N, et al. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest. 2006;116:1784–92.

    Article  PubMed  CAS  Google Scholar 

  29. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev. 2005;26:439–51.

    Article  PubMed  CAS  Google Scholar 

  30. • Lau W, Tao L, Wang Y, et al. Systemic adiponectin malfunction as a risk factor for cardiovascular disease. Antioxid Redox Signal. 2010, in press. This review summarizes the major biologic functions and intracellular pathways of adiponectin and elaborates current knowledge on adiponectin malfunction in cardiovascular disease.

  31. Zhou L, Deepa SS, Etzler JC, et al. Adiponectin activates AMP-activated protein kinase in muscle cells via APPL1/LKB1-dependent and phospholipase C/Ca2+/Ca2+/calmodulin-dependent protein kinase kinase-dependent pathways. J Biol Chem. 2009;284:22426–35.

    Article  PubMed  CAS  Google Scholar 

  32. Brochu-Gaudreau K, Rehfeldt C, Blouin R, et al. Adiponectin action from head to toe. Endocrine. 37:11–32.

  33. Yoon MJ, Lee GY, Chung JJ, et al. Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP-activated protein kinase, p38 mitogen-activated protein kinase, and peroxisome proliferator-activated receptor alpha. Diabetes. 2006;55:2562–70.

    Article  PubMed  CAS  Google Scholar 

  34. Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med. 2002;8:1288–95.

    Article  PubMed  CAS  Google Scholar 

  35. Civitarese AE, Ukropcova B, Carling S, et al. Role of adiponectin in human skeletal muscle bioenergetics. Cell Metab. 2006;4:75–87.

    Article  PubMed  CAS  Google Scholar 

  36. • Iwabu M, Yamauchi T, Okada-Iwabu M, et al. Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1. Nature. 464:1313–9. Using muscle-specific AdipoR1 KO mice and C2C12 myocytes, the authors demonstrate that adiponectin and AdipoR1 increase PGC1-α activity by Ca2+ signalling and by AMPK and SIRT, leading to increased mitochondrial biogenesis in skeletal muscle.

  37. Ikegami Y, Inukai K, Imai K, et al. Adiponectin upregulates ferritin heavy chain in skeletal muscle cells. Diabetes. 2009;58:61–70.

    Article  PubMed  CAS  Google Scholar 

  38. Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7:941–6.

    Article  PubMed  CAS  Google Scholar 

  39. Nakashima K, Yakabe Y. AMPK activation stimulates myofibrillar protein degradation and expression of atrophy-related ubiquitin ligases by increasing FOXO transcription factors in C2C12 myotubes. Biosci Biotechnol Biochem. 2007;71:1650–6.

    Article  PubMed  CAS  Google Scholar 

  40. Bolster DR, Crozier SJ, Kimball SR, Jefferson LS. AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. J Biol Chem. 2002;277:23977–80.

    Article  PubMed  CAS  Google Scholar 

  41. Zhou Q, Du J, Hu Z, et al. Evidence for adipose-muscle cross talk: opposing regulation of muscle proteolysis by adiponectin and Fatty acids. Endocrinology. 2007;148:5696–705.

    Article  PubMed  CAS  Google Scholar 

  42. • Krause MP, Liu Y, Vu V, et al. Adiponectin is expressed by skeletal muscle fibers and influences muscle phenotype and function. Am J Physiol Cell Physiol. 2008;295:C203–12. This study demonstrates that adiponectin is expressed in mouse skeletal muscle and within differentiated L6 myotubes. Moreover, adiponectin KO mice confirm the fact that absence of adiponectin causes contractile dysfunction and phenotypical changes in skeletal muscle.

    Article  PubMed  CAS  Google Scholar 

  43. Fiaschi T, Cirelli D, Comito G, et al. Globular adiponectin induces differentiation and fusion of skeletal muscle cells. Cell Res. 2009;19:584–97.

    Article  PubMed  CAS  Google Scholar 

  44. Skurk C, Wittchen F, Suckau L, et al. Description of a local cardiac adiponectin system and its deregulation in dilated cardiomyopathy. Eur Heart J. 2008;29:1168–80.

    Article  PubMed  CAS  Google Scholar 

  45. Delaigle AM, Jonas JC, Bauche IB, et al. Induction of adiponectin in skeletal muscle by inflamatory cytokines: in vivo and in vitro studies. Endocrinology. 2004;145:5589–97.

    Article  PubMed  CAS  Google Scholar 

  46. Fasshauer M, Klein J, Neumann S, et al. Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2002;290:1084–9.

    Article  PubMed  CAS  Google Scholar 

  47. Swarbrick MM, Havel PJ. Physiological, pharmacological, and nutritional regulation of circulating adiponectin concentrations in humans. Metab Syndr Relat Disord. 2008;6:87–102.

    Article  PubMed  CAS  Google Scholar 

  48. Kistorp C, Faber J, Galatius S, et al. Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure. Circulation. 2005;112:1756–62.

    Article  PubMed  CAS  Google Scholar 

  49. Sengenes C, Berlan M, De Glisezinski I, et al. Natriuretic peptides: a new lipolytic pathway in human adipocytes. FASEB J. 2000;14:1345–51.

    Article  PubMed  CAS  Google Scholar 

  50. Tsukamoto O, Fujita M, Kato M, et al. Natriuretic peptides enhance the production of adiponectin in human adipocytes and in patients with chronic heart failure. J Am Coll Cardiol. 2009;53:2070–7.

    Article  PubMed  CAS  Google Scholar 

  51. Yamaji M, Tsutamoto T, Tanaka T, et al. Effect of carperitide on plasma adiponectin levels in acute decompensated heart failure patients with diabetes mellitus. Circ J. 2009;73:2264–9.

    Article  PubMed  CAS  Google Scholar 

  52. Tanaka T, Tsutamoto T, Sakai H, et al. Effect of atrial natriuretic peptide on adiponectin in patients with heart failure. Eur J Heart Fail. 2008;10:360–6.

    Article  PubMed  CAS  Google Scholar 

  53. Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257:79–83.

    Article  PubMed  CAS  Google Scholar 

  54. Weyer C, Funahashi T, Tanaka S, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001;86:1930–5.

    Article  PubMed  CAS  Google Scholar 

  55. Hajer GR, van Haeften TW, Visseren FL. Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J. 2008;29:2959–71.

    Article  PubMed  CAS  Google Scholar 

  56. Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 2000;20:1595–9.

    PubMed  CAS  Google Scholar 

  57. Ouchi N, Kihara S, Arita Y, et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation. 1999;100:2473–6.

    PubMed  CAS  Google Scholar 

  58. Kumada M, Kihara S, Sumitsuji S, et al. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol. 2003;23:85–9.

    Article  PubMed  CAS  Google Scholar 

  59. Ouchi N, Ohishi M, Kihara S, et al. Association of hypoadiponectinemia with impaired vasoreactivity. Hypertension. 2003;42:231–4.

    Article  PubMed  CAS  Google Scholar 

  60. Chen MB, McAinch AJ, Macaulay SL, et al. Impaired activation of AMP-kinase and fatty acid oxidation by globular adiponectin in cultured human skeletal muscle of obese type 2 diabetics. J Clin Endocrinol Metab. 2005;90:3665–72.

    Article  PubMed  CAS  Google Scholar 

  61. Bruce CR, Mertz VA, Heigenhauser GJ, Dyck DJ. The stimulatory effect of globular adiponectin on insulin-stimulated glucose uptake and fatty acid oxidation is impaired in skeletal muscle from obese subjects. Diabetes. 2005;54:3154–60.

    Article  PubMed  CAS  Google Scholar 

  62. •• Mullen KL, Pritchard J, Ritchie I, et al. Adiponectin resistance precedes the accumulation of skeletal muscle lipids and insulin resistance in high-fat-fed rats. Am J Physiol Regul Integr Comp Physiol. 2009;296:R243–51. This study utilized a time-course high saturated fat feeding model to determine the early metabolic events in skeletal muscle leading to insulin resistance and demonstrated that an early loss of adiponectin’s stimulatory effect on fatty acid oxidation precedes the accumulation of intramyocellular lipids and blunted insulin signalling.

    Article  PubMed  CAS  Google Scholar 

  63. Tsutamoto T, Tanaka T, Sakai H, et al. Total and high molecular weight adiponectin, haemodynamics, and mortality in patients with chronic heart failure. Eur Heart J. 2007;28:1723–30.

    Article  PubMed  Google Scholar 

  64. Van Berendoncks AM, Beckers P, Hoymans VY, et al. Beta-blockers modify the prognostic value of adiponectin in chronic heart failure. Int J Cardiol. 2010, in press.

  65. George J, Patal S, Wexler D, et al. Circulating adiponectin concentrations in patients with congestive heart failure. Heart. 2006;92:1420–4.

    Article  PubMed  CAS  Google Scholar 

  66. Kalantar-Zadeh K, Block G, Horwich T, Fonarow G. Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure. J Am Coll Cardiol. 2004;43:1439–44.

    Article  PubMed  Google Scholar 

  67. Kalantar-Zadeh K, Horwich TB, Oreopoulos A, et al. Risk factor paradox in wasting diseases. Curr Opin Clin Nutr Metab Care. 2007;10:433–42.

    Article  PubMed  Google Scholar 

  68. Horwich TB, Fonarow GC. Reverse epidemiology beyond dialysis patients: chronic heart failure, geriatrics, rheumatoid arthritis, COPD, and AIDS. Semin Dial. 2007;20:549–53.

    Article  PubMed  Google Scholar 

  69. Guder G, Frantz S, Bauersachs J, et al. Reverse epidemiology in systolic and nonsystolic heart failure: cumulative prognostic benefit of classical cardiovascular risk factors. Circ Heart Fail. 2009;2:563–71.

    Article  PubMed  Google Scholar 

  70. Norrelund H, Wiggers H, Halbirk M, et al. Abnormalities of whole body protein turnover, muscle metabolism and levels of metabolic hormones in patients with chronic heart failure. J Intern Med. 2006;260:11–21.

    Article  PubMed  CAS  Google Scholar 

  71. Qi Y, Takahashi N, Hileman SM, et al. Adiponectin acts in the brain to decrease body weight. Nat Med. 2004;10:524–9.

    Article  PubMed  CAS  Google Scholar 

  72. McEntegart MB, Awede B, Petrie MC, et al. 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. 2007;28:829–35.

    Article  PubMed  CAS  Google Scholar 

  73. Van Berendoncks AM, Beckers P, Hoymans VY, et al. Exercise training reduces circulating adiponectin levels in patients with chronic heart failure. Clin Sci (Lond). 2009;118:281–9.

    Article  Google Scholar 

  74. Kintscher U. Does adiponectin resistance exist in chronic heart failure? Eur Heart J. 2007;28:1676–7.

    Article  PubMed  Google Scholar 

  75. • Van Berendoncks AM, Garnier A, Beckers P, et al. Functional adiponectin resistance at the level of the skeletal muscle in mild to moderate chronic heart failure. Circ Heart Fail. 2010;3:185–94. This study demonstrates a downregulation of the main adiponectin receptor, AdipoR1, and a deactivation of the downstream PPARα/AMPK pathway in skeletal muscle of patients with CHF. In addition to increased circulating and local skeletal muscle adiponectin expression, these facts suggest functional adiponectin resistance in CHF.

    Article  PubMed  Google Scholar 

  76. Van Berendoncks A, Conraads V, Van Leuven W, et al. Validation of an adiponectin immunoassay in human skeletal muscle biopsies. J Immunol Methods. 2010;362:209–12.

    Article  PubMed  Google Scholar 

  77. Tsuchida A, Yamauchi T, Ito Y, et al. Insulin/Foxo1 pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity. J Biol Chem. 2004;279:30817–22.

    Article  PubMed  CAS  Google Scholar 

  78. Sekiguchi K, Tian Q, Ishiyama M, et al. Inhibition of PPAR-alpha activity in mice with cardiac-restricted expression of tumor necrosis factor: potential role of TGF-beta/Smad3. Am J Physiol Heart Circ Physiol. 2007;292:H1443–51.

    Article  PubMed  CAS  Google Scholar 

  79. •• Liu Y, Chewchuk S, Lavigne C, et al. Functional significance of skeletal muscle adiponectin production, changes in animal models of obesity and diabetes, and regulation by rosiglitazone treatment. Am J Physiol Endocrinol Metab. 2009;297:E657–64. The authors show that skeletal muscle cells do synthesize and secrete adiponectin, which can mediate autocrine metabolic effects. This local adiponectin production is altered in animal models of obesity and diabetes.

    Article  PubMed  CAS  Google Scholar 

  80. •• Amin RH, Mathews ST, Camp HS, et al. Selective activation of PPARgamma in skeletal muscle induces endogenous production of adiponectin and protects mice from diet-induced insulin resistance. Am J Physiol Endocrinol Metab. 298:E28–37. The authors provide evidence that myocytes are capable of producing functionally active adiponectin, which stimulates the adiponectin signalling pathway, upon pharmacological activation of PPARγ.

  81. Ingelsson E, Arnlov J, Zethelius B, et al. Associations of serum adiponectin with skeletal muscle morphology and insulin sensitivity. J Clin Endocrinol Metab. 2009;94:953–7.

    Article  PubMed  CAS  Google Scholar 

  82. •• Jortay J, Senou M, Delaigle A, et al. Local induction of adiponectin reduces lipopolysaccharide-triggered skeletal muscle damage. Endocrinology. 151:4840–51. In this study, the authors provide in vitro and in vivo evidence that skeletal muscle adiponectin exerts auto/paracrine protective effects against inflammatory aggression in muscle.

  83. • Ventura-Clapier R. Exercise training, energy metabolism, and heart failure. Appl Physiol Nutr Metab. 2009;34:336–9. This review describes the alterations in molecular mechanisms of the metabolic myopathy in heart failure and the effects of endurance exercise training.

    Article  PubMed  CAS  Google Scholar 

  84. Garnier A, Fortin D, Deloménie C, et al. Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles. J Physiol. 2003;551:491–501.

    Article  PubMed  CAS  Google Scholar 

  85. Neubauer S. The failing heart—an engine out of fuel. N Engl J Med. 2007;356:1140–51.

    Article  PubMed  Google Scholar 

  86. Van Berendoncks A, Beckers P, Hoymans V, et al. The emerging role of adiponectin as a new marker of muscle wasting and exercise intolerance in chronic heart failure. Presentation at the EuroPRevent Conference, Geneva, Switzerland; April 14–16, 2011.

  87. Yamauchi T, Kamon J, Waki H, et al. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem. 2003;278:2461–8.

    Article  PubMed  CAS  Google Scholar 

  88. Viollet B, Mounier R, Leclerc J, et al. Targeting AMP-activated protein kinase as a novel therapeutic approach for the treatment of metabolic disorders. Diabetes Metab. 2007;33:395–402.

    Article  PubMed  CAS  Google Scholar 

  89. Saito Y, Fujioka D, Kawabata K, et al. Statin reverses reduction of adiponectin receptor expression in infarcted heart and in TNF-alpha-treated cardiomyocytes in association with improved glucose uptake. Am J Physiol Heart Circ Physiol. 2007;293:H3490–7.

    Article  PubMed  CAS  Google Scholar 

  90. Linke A, Adams V, Schulze PC, et al. Antioxidative effects of exercise training in patients with chronic heart failure: increase in radical scavenger enzyme activity in skeletal muscle. Circulation. 2005;111:1763–70.

    Article  PubMed  CAS  Google Scholar 

  91. Conraads V, Beckers P, Bosmans J, et al. Combined endurance/resistance training reduces plasma TNF-alpha receptor levels in patients with chronic heart failure and coronary artery disease. Eur Heart J. 2002;23:1854–60.

    Article  PubMed  CAS  Google Scholar 

  92. Conraads VM, Beckers P, Vaes J, et al. Combined endurance/resistance training reduces NT-proBNP levels in patients with chronic heart failure. Eur Heart J. 2004;25:1797–805.

    Article  PubMed  CAS  Google Scholar 

  93. Hambrecht R, Niebauer J, Fiehn E, et al. Physical training in patients with stable chronic heart failure: effects on cardiorespiratory fitness and ultrastructural abnormalities of leg muscles. J Am Coll Cardiol. 1995;25:1239–49.

    Article  PubMed  CAS  Google Scholar 

  94. Van Berendoncks A, Garnier A, Beckers P, et al. Exercise training reverses disorders of metabolic gene expression in skeletal muscle of chronic heart failure patients. Presentation at the Heart Failure WInter Research Meeting, Les Diablerets, France; January 28–30, 2010.

Download references

Acknowledgments

This work was supported by the Fund for Scientific Research, (Fonds Voor Wetenschappelijk [FWO], Flanders, Belgium). Dr. An M. Van Berendoncks is supported by a PhD fellowship. Dr. Viviane M. Conraads is granted with a Senior Clinical Investigator of the FWO.

We greatly acknowledge Professor Renée Ventura-Clapier and Professor Anne Garnier, (INSERM U-769, Univ Paris-Sud, Châtenay-Malabry, France) for their comments and the helpful discussions.

Disclosures

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to An M. Van Berendoncks.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Van Berendoncks, A.M., Conraads, V.M. Functional Adiponectin Resistance and Exercise Intolerance in Heart Failure. Curr Heart Fail Rep 8, 113–122 (2011). https://doi.org/10.1007/s11897-011-0056-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11897-011-0056-6

Keywords

Navigation