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PPAR Research
Volume 2011, Article ID 372854, 13 pages
http://dx.doi.org/10.1155/2011/372854
Research Article

Cardiomyocyte-Restricted Deletion of PPARβ/δ in PPARα-Null Mice Causes Impaired Mitochondrial Biogenesis and Defense, but No Further Depression of Myocardial Fatty Acid Oxidation

1Department of Nutrition Sciences, University of Alabama at Birmingham, 1675 University Boulevard, Birmingham, AL 35294-3360, USA
2Department of Anatomy, Second Military Medical University, Shanghai 200433, China
3Department of Cardio Thoracic Surgery, Hunan Children’s Hospital, Changsha 410007, China
4Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA 30322, USA
5Department of Anatomy, Morehouse School of Medicine, Atlanta, GA 30310, USA
6Department of Pathology, Emory University, Atlanta, GA 30322, USA

Received 30 April 2011; Revised 27 June 2011; Accepted 28 June 2011

Academic Editor: Brian Finck

Copyright © 2011 Jian Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. A. Madrazo and D. P. Kelly, “The PPAR trio: regulators of myocardial energy metabolism in health and disease,” Journal of Molecular and Cellular Cardiology, vol. 44, no. 6, pp. 968–975, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. Q. Yang and Y. Li, “Roles of PPARs on regulating myocardial energy and lipid homeostasis,” Journal of Molecular Medicine, vol. 85, no. 7, pp. 697–706, 2007. View at Publisher · View at Google Scholar · View at Scopus
  3. J. N. Feige, L. Gelman, L. Michalik, B. Desvergne, and W. Wahli, “From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions,” Progress in Lipid Research, vol. 45, no. 2, pp. 120–159, 2006. View at Publisher · View at Google Scholar · View at Scopus
  4. F. Djouadi, C. J. Weinheimer, J. E. Saffitz et al., “A gender-related defect in lipid metabolism and glucose homeostasis in peroxisome proliferator-activated receptor α-deficient mice,” The Journal of Clinical Investigation, vol. 102, no. 6, pp. 1083–1091, 1998. View at Google Scholar · View at Scopus
  5. B. N. Finck, X. Han, M. Courtois et al., “A critical role for PPARα-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: modulation by dietary fat content,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 3, pp. 1226–1231, 2003. View at Publisher · View at Google Scholar · View at Scopus
  6. K. Watanabe, H. Fujii, T. Takahashi et al., “Constitutive regulation of cardiac fatty acid metabolism through peroxisome proliferator-activated receptor α associated with age-dependent cardiac toxicity,” The Journal of Biological Chemistry, vol. 275, no. 29, pp. 22293–22299, 2000. View at Publisher · View at Google Scholar · View at Scopus
  7. T. C. Leone, C. J. Weinheimer, and D. P. Kelly, “A critical role for the peroxisome proliferator-activated receptor α (PPARα) in the cellular fasting response: the PPARα-null mouse as a model of fatty acid oxidation disorders,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 13, pp. 7473–7478, 1999. View at Publisher · View at Google Scholar · View at Scopus
  8. N. H. Son, S. Yu, J. Tuinei et al., “PPARγ-induced cardiolipotoxicity in mice is ameliorated by PPARα deficiency despite increases in fatty acid oxidation,” The Journal of Clinical Investigation, vol. 120, no. 10, pp. 3443–3454, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. B. N. Finck, J. J. Lehman, T. C. Leone et al., “The cardiac phenotype induced by PPARα overexpression mimics that caused by diabetes mellitus,” The Journal of Clinical Investigation, vol. 109, no. 1, pp. 121–130, 2002. View at Publisher · View at Google Scholar · View at Scopus
  10. A. J. Gilde, K. A. van der Lee, P. H. Willemsen et al., “Peroxisome proliferator-activated receptor (PPAR) α and PPARβ/δ, but not PPARγ, modulate the expression of genes involved in cardiac lipid metabolism,” Circulation Research, vol. 92, no. 5, pp. 518–524, 2003. View at Publisher · View at Google Scholar · View at Scopus
  11. L. Cheng, G. Ding, Q. Qin et al., “Peroxisome proliferator-activated receptor delta activates fatty acid oxidation in cultured neonatal and adult cardiomyocytes,” Biochemical and Biophysical Research Communications, vol. 313, no. 2, pp. 277–286, 2004. View at Publisher · View at Google Scholar
  12. L. Cheng, G. Ding, Q. Qin et al., “Cardiomyocyte-restricted peroxisome proliferator-activated receptor-δ deletion perturbs myocardial fatty acid oxidation and leads to cardiomyopathy,” Nature Medicine, vol. 10, no. 11, pp. 1245–1250, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. E. M. Burkart, N. Sambandam, X. Han et al., “Nuclear receptors PPARβ/δ and PPARα direct distinct metabolic regulatory programs in the mouse heart,” The Journal of Clinical Investigation, vol. 117, no. 12, pp. 3930–3939, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. J. Lee, Q. Hu, Y. Nakamura et al., “Open-chest 31P magnetic resonance spectroscopy of mouse heart at 4.7 Tesla,” Journal of Magnetic Resonance Imaging, vol. 24, no. 6, pp. 1269–1276, 2006. View at Publisher · View at Google Scholar · View at Scopus
  15. Y. Li, R. Yin, J. Liu et al., “Peroxisome proliferator-activated receptor δ regulates mitofusin 2 expression in the heart,” Journal of Molecular and Cellular Cardiology, vol. 46, no. 6, pp. 876–882, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. J. Liu, P. Wang, J. Luo et al., “Peroxisome proliferator-activated receptor ß/d activation in adult hearts facilitates mitochondrial function and cardiac performance under pressure-overload condition,” Hypertension, vol. 57, no. 2, pp. 223–230, 2011. View at Publisher · View at Google Scholar
  17. Q. Yang and L. Cheng, “Molecular regulation of lipotoxicity in the heart,” Drug Discovery Today, vol. 2, no. 1, pp. 101–107, 2005. View at Publisher · View at Google Scholar · View at Scopus
  18. Y. Li, L. Cheng, Q. Qin et al., “High-fat feeding in cardiomyocyte-restricted PPARδ knockout mice leads to cardiac overexpression of lipid metabolic genes but fails to rescue cardiac phenotypes,” Journal of Molecular and Cellular Cardiology, vol. 47, no. 4, pp. 536–543, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. J. G. Duncan, J. L. Fong, D. M. Medeiros, B. N. Finck, and D. P. Kelly, “Insulin-resistant heart exhibits a mitochondrial biogenic response driven by the peroxisome proliferator-activated receptor-α/PGC-1α gene regulatory pathway,” Circulation, vol. 115, no. 7, pp. 909–917, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. Y. Barak, D. Liao, W. He et al., “Effects of peroxisome proliferator-activated receptor δ on placentation, adiposity, and colorectal cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 1, pp. 303–308, 2002. View at Publisher · View at Google Scholar · View at Scopus
  21. R. Agah, P. A. Frenkel, B. A. French, L. H. Michael, P. A. Overbeek, and M. D. Schneider, “Gene recombination in postmitotic cells: targeted expression of Cre recombinase provokes cardiac-restricted, site-specific rearrangement in adult ventricular muscle in vivo,” The Journal of Clinical Investigation, vol. 100, no. 1, pp. 169–179, 1997. View at Google Scholar · View at Scopus
  22. P. Wang, J. Liu, Y. Li et al., “Peroxisome proliferator-activated receptor δ is an essential transcriptional regulator for mitochondrial protection and biogenesis in adult heart,” Circulation Research, vol. 106, no. 5, pp. 911–919, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. D. S. Sohal, M. Nghiem, M. A. Crackower et al., “Temporally regulated and tissue-specific gene manipulations in the adult and embryonic heart using a tamoxifen-inducible Cre protein,” Circulation Research, vol. 89, no. 1, pp. 20–25, 2001. View at Google Scholar · View at Scopus
  24. S. S. Lee, T. Pineau, J. Drago et al., “Targeted disruption of the α isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators,” Molecular & Cellular Biology, vol. 15, no. 6, pp. 3012–3022, 1995. View at Google Scholar · View at Scopus
  25. F. J. Naya, B. L. Black, H. Wu et al., “Mitochondrial deficiency and cardiac sudden death in mice lacking the MEF2A transcription factor,” Nature Medicine, vol. 8, no. 11, pp. 1303–1309, 2002. View at Publisher · View at Google Scholar · View at Scopus
  26. J. Luo, S. Wu, J. Liu et al., “Conditional PPAR? knockout from cardiomyocytes of adult mice impairs myocardial fatty acid utilization and cardiac function,” American Journal of Translational Research, vol. 3, no. 1, pp. 61–72, 2011. View at Google Scholar
  27. N. Sambandam, D. Morabito, C. Wagg, B. N. Finck, D. P. Kelly, and G. D. Lopaschuk, “Chronic activation of PPARα is detrimental to cardiac recovery after ischemia,” American Journal of Physiology, vol. 290, no. 1, pp. H87–H95, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. G. D. Lopaschuk and R. L. Barr, “Measurements of fatty acid and carbohydrate metabolism in the isolated working rat heart,” Molecular and Cellular Biochemistry, vol. 172, no. 1-2, pp. 137–147, 1997. View at Publisher · View at Google Scholar · View at Scopus
  29. T. Gulick, S. Cresci, T. Caira, D. D. Moore, and D. P. Kelly, “The peroxisome proliferator-activated receptor regulates mitochondrial fatty acid oxidative enzyme gene expression,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 23, pp. 11012–11016, 1994. View at Publisher · View at Google Scholar · View at Scopus
  30. S. Z. Duan, C. Y. Ivashchenko, M. W. Russell, D. S. Milstone, and R. M. Mortensen, “Cardiomyocyte-specffic knockout and agonist of peroxisome proliferator-activated receptor-γ both induce cardiac hypertrophy in mice,” Circulation Research, vol. 97, no. 4, pp. 372–379, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. G. Ding, M. Fu, Q. Qin et al., “Cardiac peroxisome proliferator-activated receptor γ is essential in protecting cardiomyocytes from oxidative damage,” Cardiovascular Research, vol. 76, no. 2, pp. 269–279, 2007. View at Publisher · View at Google Scholar · View at Scopus
  32. J. Luo, S. Wu, J. Liu, Y. Li et al., “Conditional PPARg knockout from cardiomyocytes of adult mice disturbs myocardial fatty acid utilization,” American Journal of Translational Research, vol. 1, pp. 59–70, 2011. View at Google Scholar