Skip to main content

Advertisement

SpringerLink
Log in

The metabolic syndrome and the heart—

a considered opinion

Insulinresistenz des Herzens

  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Zusammenfassung

Störungen des Allgemeinstoffwechsels, wie sie sich im Metabolic Syndrome manifestieren, führen zu einer Reihe von kardiovaskulären Komplikationen. Wir berichten hier über die Konsequenzen der Insulinresistenz für den Herzmuskel. Die Überlastung des Myokards mit Fettsäuren und Glukose führt zu weitreichenden funktionellen und morphologischen Veränderungen, die Virchow schon vor 150 Jahren als „fettige Atrophie“ beschrieben hat.

Summary

The metabolic syndrome (MS) is a multifactorial, heterogeneous group of risk factors for the development of cardiovascular disease. Here we review the evidence in support of the hypothesis that metabolic dysregulation of the body as a whole leads to contractile dysfunction of the heart due to an imbalance of substrate uptake (increased) and substrate oxidation (decreased). The consequences of this imbalance were already recognized 150 years ago by Virchow when he described “fatty atrophy” of the heart as a “true metamorphosis of the heart muscle cell.”

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

References

  1. Worldwide definition for the use in clinical practice (2004) The IDF consensus worldwide definition of the metabolic syndrome

  2. Allard MF (2004) Energy substrate metabolism in cardiac hypertrophy. Curr Hypertens Rep 6:430–435

    PubMed  Google Scholar 

  3. Baron AD, Brechtel-Hook G, Johnson A, Cronin J, Leaming R, Steinberg H (1996) Effect of perfusion rate on the time course of insulin-mediated skeletal muscle glucose uptake. Am J Physiol 271:E1067–1072

    CAS  PubMed  Google Scholar 

  4. Bjorkegren J, Veniant M, Kim SK, Withycombe SK, Wood PA, Hellerstein MK, Neese RA, Young SG (2001) Lipoprotein secretion and triglyceride stores in the heart. J Biol Chem 276:38511–38517

    Article  CAS  PubMed  Google Scholar 

  5. Brandt JM, Djouadi F, Kelly DP (1998) Fatty acids activate transcription of the muscle carnitine palmitoyltransferase I gene in cardiac myocytes via the peroxisome proliferator-activated receptor alpha. J Biol Chem 273:23786–23792

    Article  CAS  PubMed  Google Scholar 

  6. Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820

    Article  CAS  PubMed  Google Scholar 

  7. 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

    CAS  PubMed  Google Scholar 

  8. Cohen P (1979) The hormonal control of glycogen metabolism in mammalian muscle by multisite phosphorylation. Biochem Soc Trans 7:459–480

    CAS  PubMed  Google Scholar 

  9. Depre C, Young ME, Ying J, Ahuja HS, Han Q, Garza N, Davies PJA, Taegtmeyer H (2000) Streptozotocin-induced changes in cardiac gene expression in the absence of severe contractile dysfunction. J Mol Cell Cardiol 32:985–996

    Article  CAS  PubMed  Google Scholar 

  10. Dillmann WH (1980) Diabetes mellitus induces changes in cardiac myosin of the rat. Diabetes 29:579–582

    CAS  PubMed  Google Scholar 

  11. Dobbins RL, Szczepaniak LS, Bentley B, Esser V, Myhill J, McGarry JD (2001) Prolonged inhibition of muscle carnitine palmitoyltransferase-1 promotes intramyocellular lipid accumulation and insulin resistance in rats. Diabetes 50:123–130

    CAS  PubMed  Google Scholar 

  12. Doenst T, Goodwin GW, Cedars AM, Wang M, Stepkowski S, Taegtmeyer H (2001) Load-induced changes in vivo alter substrate fluxes and insulin responsiveness of rat heart in vitro. Metabolism 50:1083–1090

    Article  CAS  PubMed  Google Scholar 

  13. Doenst T, Taegtmeyer H (1999) Alpha-adrenergic stimulation mediates glucose uptake through phosphatidylinositol 3-kinase in rat heart. Circ Res 84:467–474

    CAS  PubMed  Google Scholar 

  14. Ferrannini E, Buzzigoli G, Bonadonna R, Giorcio MA, Oleggini M, Graziadei L, Pedrinelli R, Brandi L, Bevilacqua S (1987) Insulin resistance in essential hypertension. N Engl J Med 317:350–357

    CAS  PubMed  Google Scholar 

  15. Ford ES (2005) Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care 28:1769–1778

    PubMed  Google Scholar 

  16. Friedman JJ (2002) Fat in all the wrong places. Nature 415:268–269

    Article  CAS  PubMed  Google Scholar 

  17. Garnier A, Fortin D, Delomenie C, Momken I, Veksler V, Ventura-Clapier R (2003) Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles. J Physiol 551:491–501

    Article  CAS  PubMed  Google Scholar 

  18. Goodwin GW, Arteaga JA, Taegtmeyer H (1995) Glycogen turnover in the isolated working rat heart. J Biol Chem 270:9234–9240

    CAS  PubMed  Google Scholar 

  19. Goodwin GW, Taegtmeyer H (2000) Improved energy homeostasis of the heart in the metabolic state of exercise. Am J Physiol Heart Circ Physiol 279:H1490–H1501

    CAS  PubMed  Google Scholar 

  20. Gradinak S, Coleman GM, Taegtmeyer H, Sweeney MS, Frazier OH (1989) Improved cardiac function with glucose-insulin-potassium after coronary bypass surgery. Ann Thorac Surg 48:484–489

    Google Scholar 

  21. Grundy SM, Hansen B, Smith SC Jr, Cleeman JI, Kahn RA (2004) Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. Circulation 109:551–556

    PubMed  Google Scholar 

  22. Gulick T, Cresci S, Caira T, Moore D, Kelly D (1994) The peroxisome proliferator-activated receptor regulates mitochondrial fatty acid oxidative enzyme gene expression. Proc Natl Acad Sci USA 91:11012–11016

    CAS  PubMed  Google Scholar 

  23. Haffner S, Taegtmeyer H (2003) Epidemic obesity and the metabolic syndrome (Editorial). Circulation 108:1541–1545

    Article  PubMed  Google Scholar 

  24. Hu Y, Belke D, Suarez J, Swanson E, Clark R, Hoshijima M, Dillmann WH (2005) Adenovirus-mediated overexpression of O-GlcNA case improves contractile function in the diabetic heart. Circ Res 96:1006–1013

    Article  CAS  PubMed  Google Scholar 

  25. Jackson RJ (1993) Cytoplasmic regulation of mRNA function: the importance of the 3' untranslated region. Cell 74:9–14

    Article  CAS  PubMed  Google Scholar 

  26. Kelly DP, Scarpulla RC (2004) Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 18:357–368

    Article  CAS  PubMed  Google Scholar 

  27. Korvald C, Elvenes OP, Myrmel T (2000) Myocardial substrate metabolism influences left ventricular energetics in vivo. Am J Physiol Heart Circ Physiol 278:H1345–H1351

    CAS  PubMed  Google Scholar 

  28. Landsberg L (1986) Diet, obesity and hypertension: an hypothesis involving insulin, the sympathetic nervous system, and adaptive thermogenesis. QJ Med 61:1081–1090

    CAS  Google Scholar 

  29. Lee Y, Wang MY, Kakuma T, Wang ZW, Babcock E, McCorkle K, Higa M, Zhou YT, Unger RH (2001) Liporegulation in diet-induced obesity. The antisteatotic role of hyperleptinemia. J Biol Chem 276:5629–5635

    CAS  PubMed  Google Scholar 

  30. Lehman JJ, Barger PM, Kovacs A, Saffitz JE, Medeiros DM, Kelly DP (2000) Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest 106:847–856

    CAS  PubMed  Google Scholar 

  31. Liao R, Jain M, Cui LJDA, Aiello F, Luptak I, Ngoy S, Mortensen R, Tian R (2002) Cardiac-specific overexpression of GLUT1 prevents the development of heart failure due to pressure-overload in mice. Circulation 106:2125–2131

    Article  CAS  PubMed  Google Scholar 

  32. McClain DA, Crook ED (1996) Hexosamines and insulin resistance. Diabetes 45:1003–1009

    CAS  PubMed  Google Scholar 

  33. Modan M, Halkin H, Almog S, Lusky A, Eshkol A, Shefi M, Shitrit A, Fuchs Z (1985) Hyperinsulinemia. A link between hypertension obesity and glucose intolerance. J Clin Invest 75:809–817

    CAS  PubMed  Google Scholar 

  34. Molkentin JD, Dorn GW (2001) Cytoplasmic signaling pathyways that regulate cardiac hypertrophy. Annu Rev Physiol 63:391–426

    Article  CAS  PubMed  Google Scholar 

  35. Nemoto S, Razeghi P, Ishiyama M, De Freitas G, Taegtmeyer H, Carabello BA (2005) PPAR-gamma agonist rosiglitazone ameliorates ventricular dysfunction in experimental chronic mitral regurgitation. Am J Physiol Heart Circ Physiol 288:H77–82

    CAS  PubMed  Google Scholar 

  36. Nielsen LB, Bartels ED, Bollano E (2002) Overexpression of apolipoprotein B in the heart impedes cardiac triglyceride accumulation and development of cardiac dysfunction in diabetic mice. J Biol Chem 277:27014–27020

    CAS  PubMed  Google Scholar 

  37. Ostrander DB, Sparagna GC, Amoscato AA, McMillin JB, Dowhan W (2001) Decreased cardiolipin synthesis corresponds with cytochrome c release in palmitate-induced cardiomyocyte apoptosis. J Biol Chem 276:38061–38067

    Article  CAS  PubMed  Google Scholar 

  38. Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI (2004) Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350:664–671

    Article  CAS  PubMed  Google Scholar 

  39. Randle PJ, Garland PB, Hales CN, Newsholme EA (1963) The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785–789

    CAS  PubMed  Google Scholar 

  40. Razeghi P, Young ME, Cockrill TC, Frazier OH, Taegtmeyer H (2002) Downregulation of myocardial myocyte enhancer factor 2C and myocyte enhancer factor 2C regulated gene expression in diabetic patients with non-ischemic heart failure. Circulation 106:407–411

    Article  CAS  PubMed  Google Scholar 

  41. Reaven G (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37:1595–1607

    CAS  PubMed  Google Scholar 

  42. Reaven GM, Lithell H, Landsberg L (1996) Hypertension and associated metabolic abnormalities—the role of insulin resistance and the sympathoadrenal system. N Engl J Med 334:374–381

    Article  CAS  PubMed  Google Scholar 

  43. Ruderman N, Chisholm D, Pi-Sunyer X, Schneider S (1998) The metabolically obese, normal-weight individual revisited. Diabetes 47:699–713

    CAS  PubMed  Google Scholar 

  44. Ruderman N, Prentki M (2004) AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome. Nat Rev Drug Discov 3:340–351

    CAS  PubMed  Google Scholar 

  45. Schaffer JE (2003) Lipotoxicity: when tissues overeat. Curr Opin Lipidol 14:281–287

    Article  CAS  PubMed  Google Scholar 

  46. 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

    Article  CAS  PubMed  Google Scholar 

  47. Shulman GI (2000) Cellular mechanisms of insulin resistance. J Clin Invest 106:171–176

    CAS  PubMed  Google Scholar 

  48. Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD (1994) Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 94:1172–1179

    CAS  PubMed  Google Scholar 

  49. Swan JW, Anker SD, Walton C, Godsland IF, Clark AL, Leyva F, Stevenson JC, Coats AJ (1997) Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure. J Am Coll Cardiol 30:527–532

    Article  CAS  PubMed  Google Scholar 

  50. Taegtmeyer H (1994) Energy metabolism of the heart: from basic concepts to clinical applications. Curr Prob Cardiol 19:57–116

    Google Scholar 

  51. Taegtmeyer H (2000) Genetics of energetics: transcriptional responses in cardiac metabolism. Ann Biomed Eng 28:871–876

    Article  CAS  PubMed  Google Scholar 

  52. Taegtmeyer H, Golfman L, Sharma S, Razeghi P, Van Arsdall M (2004) Linking gene expression to function: metabolic flexibility in normal and diseased heart. Ann NY Acad Sci 1015:202–213

    CAS  PubMed  Google Scholar 

  53. Taegtmeyer H, Hems R, Krebs HA (1980) Utilization of energy-providing substrates in the isolated working rat heart. Biochem J 186:701–711

    CAS  PubMed  Google Scholar 

  54. Taegtmeyer H, McNulty P, Young ME (2002) Adaptation and maladaptation of the heart in diabetes. Part I: general concepts. Circulation 105:1727–1733

    Article  CAS  PubMed  Google Scholar 

  55. Taegtmeyer H, Overturf ML (1988) Effects of moderate hypertension on cardiac function and metabolism in the rabbit. Hypertension 11:416–426

    CAS  PubMed  Google Scholar 

  56. Unger RH (2005) Longevity, lipotoxicity and leptin: the adipocyte defense against feasting and famine. Biochimie 87:57–64

    Article  CAS  PubMed  Google Scholar 

  57. Unger RH (2005) Hyperleptinemia: protecting the heart from lipid overload. Hypertension 45:1031–1034

    Article  CAS  PubMed  Google Scholar 

  58. Unger RH, Orci L (2001) Diseases of liporegulation: new perspective on obesity and related disorders. FASEB J 15:312–321

    Article  CAS  PubMed  Google Scholar 

  59. van Bilsen M, Van der Vusse GJ, Reneman RS (1998) Transcriptional regulation of metabolic processes: implications for cardiac metabolism. Pflugers Arch 437:2–14

    Article  CAS  PubMed  Google Scholar 

  60. van der Lee K, Vork M, De Vries J, Willemsen P, Glatz J, Reneman R, Van der Vusse G, Van Bilsen M (2000) Long-chain fatty acid-induced changes in gene expression in neonatal cardiac myocytes. J Lipid Res 41:41–47

    CAS  PubMed  Google Scholar 

  61. Virchow R (1858) Die Zellularpathologie und ihre Begründung auf physiologische und pathologische Gewebelehre. Verlag von A. Hirschwald, Berlin

  62. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808

    Article  CAS  PubMed  Google Scholar 

  63. Wittels B, Spann JF (1968) Defective lipid metabolism in the failing heart. J Clin Invest 47:1787–1794

    CAS  PubMed  Google Scholar 

  64. 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

    Article  PubMed  Google Scholar 

  65. Yki-Jarvinen H, Virkamaki A, Daniels MC, McClain D, Gottschalk WK (1998) Insulin and glucosamine infusions increase O-linked N-acetyl-glucosamine in skeletal muscle proteins in vivo. Metabolism 47:449–455

    CAS  PubMed  Google Scholar 

  66. Young ME, Goodwin GW, Ying J, Guthrie P, Wilson CR, Laws FA, Taegtmeyer H (2001) Regulation of cardiac and skeletal muscle malonyl-CoA decarboxylase by fatty acids. Am J Physiol Endocrinol Metab 280:E471–E479

    CAS  PubMed  Google Scholar 

  67. Young ME, Guthrie PH, Razeghi P, Leighton B, Abbasi S, Patil S, Taegtmeyer H (2002) Impaired long chain fatty acid oxidation and contractile dysfunction in the obese Zucker rat heart. Diabetes 51:2587–2595

    CAS  PubMed  Google Scholar 

  68. Young ME, McNulty P, Taegtmeyer H (2002) Adaptation and maladaptation of the heart in diabetes. Part II: potential mechanisms. Circulation 105:1861–1870

    Article  CAS  PubMed  Google Scholar 

  69. Young ME, Patil S, Ying J, Depre C, Ahuja HS, Shipley GL, Stepkowski SM, Davies PJA, Taegtmeyer H (2001) Uncoupling protein 3 transcription is regulated by peroxisome proliferator-activated receptor (alpha) in the adult rodent heart. FASEB J 15:833–845

    Article  CAS  PubMed  Google Scholar 

  70. Zachara NE, Hart GW (2004) OGlcNAc a sensor of cellular state: the role of nucleocytoplasmic glycosylation in modulating cellular function in response to nutrition and stress. Biochim Biophys Acta 1673:13–28

    CAS  PubMed  Google Scholar 

  71. Zhou YT, Grayburn P, Karim A, Shimabukuro M, Higa M, Baetens D, Orci L, Unger RH (2000) Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci USA 97:1784–1789

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The University of Texas Houston Medical School, Department of Internal Medicine, Division of Cardiology, 6431 Fannin Street, MSB 1.246, Houston, TX 77030, USA

    J. G. Leichman MD, V. R. Lavis MD, D. Aguilar MD, C. R. Wilson BS & H. Taegtmeyer MD DPhil

Authors
  1. J. G. Leichman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. R. Lavis MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Aguilar MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. R. Wilson BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. Taegtmeyer MD DPhil
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Taegtmeyer MD DPhil.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leichman, J.G., Lavis, V.R., Aguilar, D. et al. The metabolic syndrome and the heart—. Clin Res Cardiol 95 (Suppl 1), i134–i141 (2006). https://doi.org/10.1007/s00392-006-1119-7

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-006-1119-7

Schlüsselwörter

Key words

Search

Navigation