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Effects of insulin-like growth factor-I on the maturation of metabolism in neonatal rat cardiomyocytes

  • Cardiovascular System
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Abstract

Myocardial metabolism shifts during the perinatal period from predominant utilization of glucose towards oxidation of fatty acids. Expression of enzymes of the fatty acid oxidation (FAO) pathway is under the control of the nuclear receptor/transcription factor peroxisome proliferator-activated receptor α (PPARα). Insulin-like Growth Factor-I (IGF-I) plays an important role in the post-natal growth and differentiation of the heart. We determined the influence of IGF-I on the maturation of myocardial metabolism. In neonatal rat cardiac myocytes, expression of the FAO enzymes MCAD and M-CPT I was induced by treatment with the specific PPARα agonist WY-14643. Concomitant treatment with IGF-I enhanced the expression of both FAO enzymes. By comparison, treatment with FGF-2, which is required for myocyte differentiation of cardiac precursors, did not increase WY-14643-induced expression of FAO enzymes. Despite stimulation of FAO enzyme expression, IGF-I did not further enhance WY-14643-stimulated palmitate oxidation. In contrast, IGF-I relieved WY-14643-mediated inhibition of glucose uptake and promoted storage of fatty acids into cellular neutral lipids. In conclusion, IGF-I promotes a more mature pattern of FAO gene expression but, because of insulin-like metabolic effects, does not concomitantly enhance oxidation of fatty acids.

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References

  1. Aranda A, Pascual A (2001) Nuclear hormone receptors and gene expression. Physiol Rev 81:1269–1304

    PubMed  CAS  Google Scholar 

  2. Barger PM, Brandt JM, Leone TC, Weinheimer CJ, Kelly DP (2000) Deactivation of peroxisome proliferator-activated receptor-α during cardiac hypertrophic growth. J Clin Invest 105:1723–1730

    Article  PubMed  CAS  Google Scholar 

  3. Barger PM, Browning AC, Garner AN, Kelly DP (2001) p38 Mitogen-activated protein kinase activates peroxisome proliferator-activated receptor α. A potential role in the cardiac metabolic stress response. J Biol Chem 276:44495–44501

    Article  PubMed  CAS  Google Scholar 

  4. Bartelds B, Gratama J-WC, Knoester H, Takens J, Smid GB, Aarnoudse JG, Heymans HSA, Kuipers JRG (1998) Perinatal changes in myocardial supply and flux of fatty acids, carbohydrates, and ketone bodies in lambs. Am J Physiol 274:H1962–H1969

    PubMed  CAS  Google Scholar 

  5. Bartelds B, Takens J, Smid GB, Zammit VA, Prip-Buus C, Kuipers JRG, van der Leij FR (2004) Myocardial carnitine palmitoyltransferase I expression and long-chain fatty acid oxidation in fetal and newborn lambs. Am J Physiol 286:H2243–H2248

    CAS  Google Scholar 

  6. 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  PubMed  CAS  Google Scholar 

  7. Braz JC, Bueno OF, Liang Q, Wilkins BJ, Dai Y-S, Parsons S, Braunwart J, Glascock BJ, Klevitsky R, Kimball TF, Hewett TE, Molkentin JD (2003) Targeted inhibition of p38 MAPK promotes hypertrophic cardiomyopathy through upregulation of calcineurin-NFAT signaling. J Clin Invest 111:1475–1486

    Article  PubMed  CAS  Google Scholar 

  8. Cook GA, Edwards TL, Jansen MS, Bahouth SW, Wilcox HG, Park EA (2001) Differential regulation of carnitine palmitoyltransferase-I gene isoforms (CPT-Iα and CPT-Iβ ) in the Rat Heart. J Mol Cell Cardiol 33:317–329

    Article  PubMed  CAS  Google Scholar 

  9. De Vries J, Vork M, Roemen T, de Jong Y, Cleutjens J, van der Vusse G, van Bilsen M (1997) Saturated but not mono-unsaturated fatty acids induce apoptotic cell death in neonatal rat ventricular myocytes. J Lipid Res 38:1384–1394

    PubMed  Google Scholar 

  10. Donath MY, Zapf J, Eppenberger-Eberhardt M, Froesch ER, Eppenberger HM (1994) Insulin-like growth factor I stimulates myofibril development and decreases smooth muscle α-actin of adult cardiomyocytes. Proc Natl Acad Sci U S A 91:1686–1690

    Article  PubMed  CAS  Google Scholar 

  11. Fischer Y, Rose H, Kammermeier H (1991) Highly insulin-responsive isolated rat heart muscle cells yielded by a modified isolation method. Life Sci 49:1679–1688

    Article  PubMed  CAS  Google Scholar 

  12. Foncea R, Andersson M, Ketterman A, Blakesley V, Sapag-Hagar M, Sugden PH, LeRoith D, Lavandero S (1997) Insulin-like growth factor-I rapidly activates multiple signal transduction pathways in cultured rat cardiac myocytes. J Biol Chem 272:19115–19124

    Article  PubMed  CAS  Google Scholar 

  13. Gilde AJ, van der Lee KAJM, Willemsen PHM, Chinetti G, van der Leij FR, van der Vusse GJ, Staels B, van Bilsen M (2003) Peroxisome Proliferator-Activated Receptor (PPAR)α and PPARβ/δ, but not PPARγ, modulate the expression of genes involved in cardiac lipid metabolism. Circ Res 92:518–524

    Article  PubMed  CAS  Google Scholar 

  14. Girard J, Ferre P, Pegorier JP, Duee PH (1992) Adaptations of glucose and fatty acid metabolism during perinatal period and suckling-weaning transition. Physiol Rev 72:507–562

    PubMed  CAS  Google Scholar 

  15. 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 U S A 91:11012–11016

    Article  PubMed  CAS  Google Scholar 

  16. Hudson EK, Wang D, Bieber LL, Buja LM, McMillin JB (1996) Increased carnitine palmitoyltransferase in cardiac myocytes is mediated by insulin growth factor I. Am J Physiol 271:H422–H427

    PubMed  CAS  Google Scholar 

  17. Isgaard J, Nilsson A, Vikman K, Isaksson O (1989) Growth hormone regulates the level of insulin-like growth factor-I mRNA in rat skeletal muscle. J Endocrinol 120:107–112

    Article  PubMed  CAS  Google Scholar 

  18. Ito H, Hiroe M, Hirata Y, Tsujino M, Adachi S, Shichiri M, Koike A, Nogami A, Marumo F (1993) Insulin-like growth factor-I induces hypertrophy with enhanced expression of muscle specific genes in cultured rat cardiomyocytes. Circulation 87:1715–1721

    PubMed  CAS  Google Scholar 

  19. Kelly D, Gordon J, Alpers R, Strauss A (1989) The tissue-specific expression and developmental regulation of two nuclear genes encoding rat mitochondrial proteins. Medium chain acyl- CoA dehydrogenase and mitochondrial malate dehydrogenase. J Biol Chem 264:18921–18925

    PubMed  CAS  Google Scholar 

  20. Lopaschuk GD, Spafford MA, Marsh DR (1991) Glycolysis is predominant source of myocardial ATP production immediately after birth. Am J Physiol 261:H1698–H1705

    PubMed  CAS  Google Scholar 

  21. Lopaschuk GD, Witters LA, Itoi T, Barr R, Barr A (1994) Acetyl-CoA carboxylase involvement in the rapid maturation of fatty acid oxidation in the newborn rabbit heart. J Biol Chem 269:25871–25878

    PubMed  CAS  Google Scholar 

  22. Mathews L, Enberg B, Norstedt G (1989) Regulation of rat growth hormone receptor gene expression. J Biol Chem 264:9905–9910

    PubMed  CAS  Google Scholar 

  23. Montessuit C, Rosenblatt-Velin N, Papageorgiou I, Campos L, Pellieux C, Palma T, Lerch R (2004) Regulation of glucose transporters expression in cardiac myocytes: p38 MAPK is a strong inductor of GLUT4. Cardiovasc Res 64:94–104

    Article  PubMed  CAS  Google Scholar 

  24. Nagao M, Parimoo B, Tanaka K (1993) Developmental, nutritional, and hormonal regulation of tissue-specific expression of the genes encoding various acyl-CoA dehydrogenases and α-subunit of electron transfer flavoprotein in rat. J Biol Chem 268:24114–24124

    PubMed  CAS  Google Scholar 

  25. Postic C, Leturque A, Printz RL, Maulard P, Loizeau M, Granner DK, Girard J (1994) Development and regulation of glucose transporter and hexokinase expression in rat. Am J Physiol 266:E548–E559

    PubMed  CAS  Google Scholar 

  26. Randle P (1998) Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab Rev 14:263–283

    Article  PubMed  CAS  Google Scholar 

  27. Rosenblatt-Velin N, Lepore MG, Cartoni C, Beermann F, Pedrazzini T (2005) FGF-2 controls the differentiation of resident cardiac precursors into functional cardiomyocytes. J Clin Invest 115:1724–1733

    Article  PubMed  CAS  Google Scholar 

  28. Studelska DR, Campbell C, Pang S, Rodnick KJ, James DE (1992) Developmental expression of insulin-regulatable glucose transporter GLUT-4. Am J Physiol 263:E102–E106

    PubMed  CAS  Google Scholar 

  29. Takahashi T, Fukuda K, Pan J, Kodama H, Sano M, Makino S, Kato T, Manabe T, Ogawa S (1999) Characterization of insulin-like growth factor-1-induced activation of the JAK/STAT pathway in rat cardiomyocytes. Circ Res 85:884–891

    PubMed  CAS  Google Scholar 

  30. Thorburn J, McMahon M, Thorburn A (1994) Raf-1 kinase activity is necessary and sufficient for gene expression changes but not sufficient for cellular morphology changes associated with cardiac myocyte hypertrophy. J Biol Chem 269:30580–30586

    PubMed  CAS  Google Scholar 

  31. Van der Lee KAJM, Vork MM, De Vries JE, Willemsen PHM, Glatz JFC, Reneman RS, Van der Vusse GJ, Van Bilsen M (2000) Long-chain fatty acid-induced changes in gene expression in neonatal cardiac myocytes. J Lipid Res 41:41–47

    PubMed  Google Scholar 

  32. Wang C, Hu S-M (1991) Developmental regulation in the expression of rat heart glucose transporters. Biochem Biophys Res Commun 177:1095–1100

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Cardiology, Department of Internal Medicine, Geneva University Hospitals, 24 Micheli-du-Crest, 1211, Geneva 14, Switzerland

    Christophe Montessuit, Tatiana Palma, Christelle Viglino, Corinne Pellieux & René Lerch

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  1. Christophe Montessuit
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  2. Tatiana Palma
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  3. Christelle Viglino
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  4. Corinne Pellieux
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  5. René Lerch
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Correspondence to Christophe Montessuit.

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Montessuit, C., Palma, T., Viglino, C. et al. Effects of insulin-like growth factor-I on the maturation of metabolism in neonatal rat cardiomyocytes. Pflugers Arch - Eur J Physiol 452, 380–386 (2006). https://doi.org/10.1007/s00424-006-0059-4

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  • DOI: https://doi.org/10.1007/s00424-006-0059-4

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