Basic Research in Cardiology

, Volume 101, Issue 1, pp 17–26 | Cite as

Cardiac fatty acid metabolism is preserved in the compensated hypertrophic rat heart

  • H. Degens
  • K. F. J. de Brouwer
  • A. J. Gilde
  • M. Lindhout
  • P. H. M. Willemsen
  • B. J. Janssen
  • G. J. van der Vusse
  • M. van BilsenEmail author


Cardiac hypertrophy and failure are associated with alterations in cardiac substrate metabolism. It remains to be established, however, whether genomically driven changes in cardiac glucose and fatty acid (FA) metabolism represent a key event of the hypertrophic remodeling process. Accordingly, we investigated metabolic gene expression and substrate metabolism during compensatory hypertrophy, in relation to other cardiac remodeling processes.

Thereto, cardiac hypertrophy was induced in rats by supra–renal aortic constriction to various degrees, resulting in increased heart/body weight ratios of 22% (Aob–1), 24% (Aob–2) and 32% (Aob–3) (p < 0.005) after 4 weeks. The unaltered ejection fraction in all groups indicated that the hypertrophy was still compensatory in nature. β–Myosin Heavy Chain protein and ANF mRNA levels were increased in all groups. Only in Aob–3 rats were SERCA2a mRNA levels markedly reduced. In this group, glycolytic capacity was modestly elevated (+ 25%; p < 0.01). Notwithstanding these phenotypical changes, the expression of genes involved in FA metabolism and FA oxidation rate in cardiac homogenates was completely preserved, irrespective of the degree of hypertrophy. These findings indicate that cardiac FA oxidative capacity is preserved during compensatory hypertrophy, and that a decline in metabolic gene expression does not represent a hallmark of the development of hypertrophy.

Key words

metabolism glucose fatty acids gene expression hypertrophy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Allard MF, Schonekess BO, Henning SL, English DR, Lopaschuk GD (1994) Contribution of oxidative metabolism and glycolysis to ATP production in hypertrophied hearts. Am J Physiol 267:H742–H750PubMedGoogle Scholar
  2. 2.
    Arai M, Suzuki T, Nagai R (1996) Sarcoplasmic reticulum genes are upregulated in mild cardiac hypertrophy but downregulated in severe cardiac hypertrophy induced by pressure overload. J Mol Cell Cardiol 28:1583–1590PubMedCrossRefGoogle Scholar
  3. 3.
    Barger PM, Brandt JM, Leone TC, Weinheimer CJ, Kelly DP (2000) Deactivation of peroxisome proliferator-activated receptor-alpha during cardiac hypertrophic growth. J Clin Invest 105:1723–1730PubMedCrossRefGoogle Scholar
  4. 4.
    Burgess ML, Buggy J, Price RL, Abel FL, Terracio L, Samarel AM, Borg TK (1996) Exercise- and hypertension-induced collagen changes are related to left ventricular function in rat hearts. Am J Physiol 270:H151–H159PubMedGoogle Scholar
  5. 5.
    Buttrick PM, Kaplan M, Leinwand LA, Scheuer J (1994) Alterations in gene expression in the rat heart after chronic pathological and physiological loads. J Mol Cell Cardiol 26:61–67PubMedCrossRefGoogle Scholar
  6. 6.
    Chandler MP, Kerner J, Huang H, Vazquez E, Reszko A, Martini WZ, Hoppel CL, Imai M, Rastogi S, Sabbah HN, Stanley WC (2004) Moderate severity heart failure does not involve a downregulation of myocardial fatty acid oxidation. Am J Physiol 287:H1538–H1543Google Scholar
  7. 7.
    Chang KC, Figueredo VM, Schreur JH, Kariya K, Weiner MW, Simpson PC, Camacho SA (1997) Thyroid hormone improves function and Ca2+ handling in pressure overload hypertrophy. Association with increased sarcoplasmic reticulum Ca2+-ATPase and alpha-myosin heavy chain in rat hearts. J Clin Invest 100:1742–1749PubMedGoogle Scholar
  8. 8.
    Cornelussen R, Spiering W, Webers JH, De Bruin LG, Reneman RS, van der Vusse GJ, Snoeckx LH (1994) Heat shock improves ischemic tolerance of hypertrophied rat hearts. Am J Physiol 267:H1941–H1947PubMedGoogle Scholar
  9. 9.
    de las Fuentes L, Herrero P, Peterson LR, Kelly DP, Gropler RJ, Davila-Roman VG (2003) Myocardial fatty acid metabolism: independent predictor of left ventricular mass in hypertensive heart disease. Hypertension 41:83–87PubMedCrossRefGoogle Scholar
  10. 10.
    Degens H, Gilde AJ, Lindhout M, Willemsen PH, Van Der Vusse GJ, Van Bilsen M (2003) Functional and metabolic adaptation of the heart to prolonged thyroid hormone treatment. Am J Physiol 284:H108–H115Google Scholar
  11. 11.
    Doenst T, Goodwin GW, Cedars AM, Wang M, Stepkowski S, Taegtmeyer H (2001) Load-induced changes in vivo alter substrate .uxes and insulin responsiveness of rat heart in vitro. Metabolism 50:1083–1090PubMedCrossRefGoogle Scholar
  12. 12.
    El Alaoui-Talibi Z, Guendouz A, Moravec M, Moravec J (1997) Control of oxidative metabolism in volume-overloaded rat hearts: effect of propionyl-L-carnitine. Am J Physiol 272:H1615–H1624PubMedGoogle Scholar
  13. 13.
    Feldman AM, Weinberg EO, Ray PE, Lorell BH (1993) Selective changes in cardiac gene expression during compensated hypertrophy and the transition to cardiac decompensation in rats with chronic aortic banding. Circ Res 73:184–192PubMedGoogle Scholar
  14. 14.
    Hasenfuss G, Reinecke H, Studer R, Pieske B, Meyer M, Drexler H, Just H (1996) Calcium cycling proteins and force-frequency relationship in heart failure. Basic Res Cardiol 91 (Suppl 2):17–22PubMedCrossRefGoogle Scholar
  15. 15.
    Kalsi KK, Smolenski RT, Pritchard RD, Khaghani A, Seymour AM, Yacoub MH (1999) Energetics and function of the failing human heart with dilated or hypertrophic cardiomyopathy. Eur J Clin Invest 29:469–477PubMedCrossRefGoogle Scholar
  16. 16.
    Kissling G (1980) Oxygen consumption and substrate uptake of the hypertrophied rat heart in situ. Basic Res Cardiol 75:185–192PubMedCrossRefGoogle Scholar
  17. 17.
    Miyamoto T, Takeishi Y, Tazawa S, Inoue M, Aoyama T, Takahashi H, Arimoto T, Shishido T, Tomoike H, Kubota I (2004) Fatty acid metabolism assessed by 125Iiodophenyl 9-methylpentadecanoic acid (9MPA) and expression of fatty acid utilization enzymes in volume-overloaded hearts. Eur J Clin Invest 34:176–181PubMedCrossRefGoogle Scholar
  18. 18.
    Osorio JC, Stanley WC, Linke A, Castellari M, Diep QN, Panchal AR, Hintze TH, Lopaschuk GD, Recchia FA (2002) Impaired myocardial fatty acid oxidation and reduced protein expression of retinoid X receptor-alpha in pacinginduced heart failure. Circulation 106:606–612PubMedCrossRefGoogle Scholar
  19. 19.
    Razeghi P, Young ME, Alcorn JL, Moravec CS, Frazier OH, Taegtmeyer H (2001) Metabolic gene expression in fetal and failing human heart. Circulation 104:2923–2931PubMedGoogle Scholar
  20. 20.
    Remondino A, Rosenblatt-Velin N, Montessuit C, Tardy I, Papageorgiou I, Dorsaz PA, Jorge-Costa M, Lerch R (2000) Altered expression of proteins of metabolic regulation during remodeling of the left ventricle after myocardial infarction. J Mol Cell Cardiol 32:2025–2034Google Scholar
  21. 21.
    Rosenblatt-Velin N, Montessuit C, Papageorgiou I, Terrand J, Lerch R (2001) Postinfarction heart failure in rats is associated with upregulation of GLUT-1 and downregulation of genes of fatty acid metabolism. Cardiovasc Res 52:407–416PubMedCrossRefGoogle Scholar
  22. 22.
    Sack MN, Disch DL, Rockman HA, Kelly DP (1997) A role for Sp and nuclear receptor transcription factors in a cardiac hypertrophic growth program. Proc Natl Acad Sci USA 94:6438–6443PubMedCrossRefGoogle Scholar
  23. 23.
    Sack MN, Harrington LS, Jonassen AK, Mjos OD, Yellon DM (2000) Coordinate regulation of metabolic enzyme encoding genes during cardiac development and following carvedilol therapy in spontaneously hypertensive rats. Cardiovasc Drugs Ther 14:31–39PubMedCrossRefGoogle Scholar
  24. 24.
    Sack MN, Rader TA, Park S, Bastin J, McCune SA, Kelly DP (1996) Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. Circulation 94:2837–2842PubMedGoogle Scholar
  25. 25.
    Schonekess BO, Allard MF, Lopaschuk GD (1995) Propionyl L-carnitine improvement of hypertrophied heart function is accompanied by an increase in carbohydrate oxidation. Circ Res 77:726–734PubMedGoogle Scholar
  26. 26.
    Shimoyama M, Hayashi D, Takimoto E, Zou Y, Oka T, Uozumi H, Kudoh S, Shibasaki F, Yazaki Y, Nagai R, Komuro I (1999) Calcineurin plays a critical role in pressure overload-induced cardiac hypertrophy. Circulation 100:2449–2454PubMedGoogle Scholar
  27. 27.
    Stanley WC, Recchia FA, Lopaschuk GD (2005) Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 85:1093–1129PubMedGoogle Scholar
  28. 28.
    Steinmetz M, Quentin T, Poppe A, Paul T, Jux C (2005) Changes in expression levels of genes involved in fatty acid metabolism: upregulation of all three members of the PPAR family (alpha, gamma, delta) and the newly described adiponectin receptor 2, but not adiponectin receptor 1 during neonatal cardiac development of the rat. Basic Res Cardiol 100:263–269PubMedCrossRefGoogle Scholar
  29. 29.
    Taegtmeyer H (2002) Switching metabolic genes to build a better heart. Circulation 106:2043–2045PubMedCrossRefGoogle Scholar
  30. 30.
    Takeo S, Elmoselhi AB, Goel R, Sentex E, Wang J, Dhalla NS (2000) Attenuation of changes in sarcoplasmic reticular gene expression in cardiac hypertrophy by propranolol and verapamil. Mol Cell Biochem 213:111–118PubMedCrossRefGoogle Scholar
  31. 31.
    van Bilsen M, Smeets PJ, Gilde AJ, van der Vusse GJ (2004) Metabolic remodelling of the failing heart: the cardiac burn-out syndrome? Cardiovasc Res 61:218–226PubMedGoogle Scholar
  32. 32.
    Van der Lee KA, Willemsen PH, Samec S, Seydoux J, Dulloo AG, Pelsers MM, Glatz JF, Van der Vusse GJ, Van Bilsen M (2001) Fasting-induced changes in the expression of genes controlling substrate metabolism in the rat heart. J Lipid Res 42:1752–1758PubMedGoogle Scholar
  33. 33.
    Young ME, Laws FA, Goodwin GW, Taegtmeyer H (2001) Reactivation of peroxisome proliferator-activated receptor alpha is associated with contractile dysfunction in hypertrophied rat heart. J Biol Chem 276:44390–44395PubMedGoogle Scholar

Copyright information

© Steinkopff-Verlag 2006

Authors and Affiliations

  • H. Degens
    • 1
  • K. F. J. de Brouwer
    • 1
  • A. J. Gilde
    • 1
  • M. Lindhout
    • 1
  • P. H. M. Willemsen
    • 1
  • B. J. Janssen
    • 2
  • G. J. van der Vusse
    • 1
  • M. van Bilsen
    • 1
    Email author
  1. 1.Dep. of PhysiologyCardiovascular Research Institute Maastricht (CARIM) Maastricht UniversityMaastrichtthe Netherlands
  2. 2.Dep. of PharmacologyCardiovascular Research Institute Maastricht (CARIM) Maastricht UniversityMaastrichtthe Netherlands

Personalised recommendations