This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Huss, J. M.
Right arrow Articles by Kelly, D. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Huss, J. M.
Right arrow Articles by Kelly, D. P.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2004, p. 9079-9091, Vol. 24, No. 20
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.20.9079-9091.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Estrogen-Related Receptor {alpha} Directs Peroxisome Proliferator-Activated Receptor {alpha} Signaling in the Transcriptional Control of Energy Metabolism in Cardiac and Skeletal Muscle

Janice M. Huss,1 Inés Pineda Torra,2,{dagger} Bart Staels,2 Vincent Giguère,3 and Daniel P. Kelly1*

Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, Missouri,1 Départment d' Athérosclérose, Institut Pasteur de Lille, Université de Lille II, Lille, France,2 Molecular Oncology, McGill University Health Centre, Montreal, Quebec, Canada3

Received 26 February 2004/ Returned for modification 23 April 2004/ Accepted 26 July 2004

Estrogen-related receptors (ERRs) are orphan nuclear receptors activated by the transcriptional coactivator peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) coactivator 1{alpha} (PGC-1{alpha}), a critical regulator of cellular energy metabolism. However, metabolic target genes downstream of ERR{alpha} have not been well defined. To identify ERR{alpha}-regulated pathways in tissues with high energy demand such as the heart, gene expression profiling was performed with primary neonatal cardiac myocytes overexpressing ERR{alpha}. ERR{alpha} upregulated a subset of PGC-1{alpha} target genes involved in multiple energy production pathways, including cellular fatty acid transport, mitochondrial and peroxisomal fatty acid oxidation, and mitochondrial respiration. These results were validated by independent analyses in cardiac myocytes, C2C12 myotubes, and cardiac and skeletal muscle of ERR{alpha}–/– mice. Consistent with the gene expression results, ERR{alpha} increased myocyte lipid accumulation and fatty acid oxidation rates. Many of the genes regulated by ERR{alpha} are known targets for the nuclear receptor PPAR{alpha}, and therefore, the interaction between these regulatory pathways was explored. ERR{alpha} activated PPAR{alpha} gene expression via direct binding of ERR{alpha} to the PPAR{alpha} gene promoter. Furthermore, in fibroblasts null for PPAR{alpha} and ERR{alpha}, the ability of ERR{alpha} to activate several PPAR{alpha} targets and to increase cellular fatty acid oxidation rates was abolished. PGC-1{alpha} was also shown to activate ERR{alpha} gene expression. We conclude that ERR{alpha} serves as a critical nodal point in the regulatory circuitry downstream of PGC-1{alpha} to direct the transcription of genes involved in mitochondrial energy-producing pathways in cardiac and skeletal muscle.

* Corresponding author. Mailing address: Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, MO 63110. Phone: (314) 362-8908. Fax: (314) 362-0186. E-mail: dkelly{at}im.wustl.edu.

{dagger} Present address: New York University Medical Center, New York, N.Y.

Molecular and Cellular Biology, October 2004, p. 9079-9091, Vol. 24, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.20.9079-9091.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nakagawa, Y., Kuwahara, K., Takemura, G., Akao, M., Kato, M., Arai, Y., Takano, M., Harada, M., Murakami, M., Nakanishi, M., Usami, S., Yasuno, S., Kinoshita, H., Fujiwara, M., Ueshima, K., Nakao, K. (2009). p300 Plays a Critical Role in Maintaining Cardiac Mitochondrial Function and Cell Survival in Postnatal Hearts. Circ. Res. 105: 746-754 [Abstract] [Full Text]  
  • Delhon, I., Gutzwiller, S., Morvan, F., Rangwala, S., Wyder, L., Evans, G., Studer, A., Kneissel, M., Fournier, B. (2009). Absence of Estrogen Receptor-Related-{alpha} Increases Osteoblastic Differentiation and Cancellous Bone Mineral Density. Endocrinology 150: 4463-4472 [Abstract] [Full Text]  
  • Bianco, S., Lanvin, O., Tribollet, V., Macari, C., North, S., Vanacker, J.-M. (2009). Modulating Estrogen Receptor-related Receptor-{alpha} Activity Inhibits Cell Proliferation. J. Biol. Chem. 284: 23286-23292 [Abstract] [Full Text]  
  • Grasfeder, L. L., Gaillard, S., Hammes, S. R., Ilkayeva, O., Newgard, C. B., Hochberg, R. B., Dwyer, M. A., Chang, C.-y., McDonnell, D. P. (2009). Fasting-Induced Hepatic Production of DHEA Is Regulated by PGC-1{alpha}, ERR{alpha}, and HNF4{alpha}. Mol. Endocrinol. 23: 1171-1182 [Abstract] [Full Text]  
  • Yang, J., Williams, R. S., Kelly, D. P. (2009). Bcl3 Interacts Cooperatively with Peroxisome Proliferator-Activated Receptor Gamma (PPAR{gamma}) Coactivator 1{alpha} To Coactivate Nuclear Receptors Estrogen-Related Receptor {alpha} and PPAR{alpha}. Mol. Cell. Biol. 29: 4091-4102 [Abstract] [Full Text]  
  • Kleiner, S., Nguyen-Tran, V., Bare, O., Huang, X., Spiegelman, B., Wu, Z. (2009). PPAR{delta} Agonism Activates Fatty Acid Oxidation via PGC-1{alpha} but Does Not Increase Mitochondrial Gene Expression and Function. J. Biol. Chem. 284: 18624-18633 [Abstract] [Full Text]  
  • Chisamore, M. J., Wilkinson, H. A., Flores, O., Chen, J. D. (2009). Estrogen-related receptor-{alpha} antagonist inhibits both estrogen receptor-positive and estrogen receptor-negative breast tumor growth in mouse xenografts. Molecular Cancer Therapeutics 8: 672-681 [Abstract] [Full Text]  
  • Lin, J. D. (2009). Minireview: The PGC-1 Coactivator Networks: Chromatin-Remodeling and Mitochondrial Energy Metabolism. Mol. Endocrinol. 23: 2-10 [Abstract] [Full Text]  
  • Hallberg, M., Morganstein, D. L., Kiskinis, E., Shah, K., Kralli, A., Dilworth, S. M., White, R., Parker, M. G., Christian, M. (2008). A Functional Interaction between RIP140 and PGC-1{alpha} Regulates the Expression of the Lipid Droplet Protein CIDEA. Mol. Cell. Biol. 28: 6785-6795 [Abstract] [Full Text]  
  • Stein, R. A., Chang, C.-y., Kazmin, D. A., Way, J., Schroeder, T., Wergin, M., Dewhirst, M. W., McDonnell, D. P. (2008). Estrogen-Related Receptor {alpha} Is Critical for the Growth of Estrogen Receptor-Negative Breast Cancer. Cancer Res. 68: 8805-8812 [Abstract] [Full Text]  
  • Giguere, V. (2008). Transcriptional Control of Energy Homeostasis by the Estrogen-Related Receptors. Endocr. Rev. 29: 677-696 [Abstract] [Full Text]  
  • Teyssier, C., Bianco, S., Lanvin, O., Vanacker, J.-M. (2008). The orphan receptor ERR{alpha} interferes with steroid signaling. Nucleic Acids Res 36: 5350-5361 [Abstract] [Full Text]  
  • Hummasti, S., Tontonoz, P. (2008). Adopting New Orphans into the Family of Metabolic Regulators. Mol. Endocrinol. 22: 1743-1753 [Abstract] [Full Text]  
  • Lai, L., Leone, T. C., Zechner, C., Schaeffer, P. J., Kelly, S. M., Flanagan, D. P., Medeiros, D. M., Kovacs, A., Kelly, D. P. (2008). Transcriptional coactivators PGC-1{alpha} and PGC-l{beta} control overlapping programs required for perinatal maturation of the heart. Genes Dev. 22: 1948-1961 [Abstract] [Full Text]  
  • Lehman, J. J., Boudina, S., Banke, N. H., Sambandam, N., Han, X., Young, D. M., Leone, T. C., Gross, R. W., Lewandowski, E. D., Abel, E. D., Kelly, D. P. (2008). The transcriptional coactivator PGC-1{alpha} is essential for maximal and efficient cardiac mitochondrial fatty acid oxidation and lipid homeostasis. Am. J. Physiol. Heart Circ. Physiol. 295: H185-H196 [Abstract] [Full Text]  
  • Pearen, M. A., Myers, S. A., Raichur, S., Ryall, J. G., Lynch, G. S., Muscat, G. E. O. (2008). The Orphan Nuclear Receptor, NOR-1, a Target of {beta}-Adrenergic Signaling, Regulates Gene Expression that Controls Oxidative Metabolism in Skeletal Muscle. Endocrinology 149: 2853-2865 [Abstract] [Full Text]  
  • Hu, P., Kinyamu, H. K., Wang, L., Martin, J., Archer, T. K., Teng, C. (2008). Estrogen Induces Estrogen-related Receptor {alpha} Gene Expression and Chromatin Structural Changes in Estrogen Receptor (ER)-positive and ER-negative Breast Cancer Cells. J. Biol. Chem. 283: 6752-6763 [Abstract] [Full Text]  
  • Tremblay, A. M., Wilson, B. J., Yang, X.-J., Giguere, V. (2008). Phosphorylation-Dependent Sumoylation Regulates Estrogen-Related Receptor-{alpha} and -{gamma} Transcriptional Activity through a Synergy Control Motif. Mol. Endocrinol. 22: 570-584 [Abstract] [Full Text]  
  • Akter, Mst. H., Chano, T., Okabe, H., Yamaguchi, T., Hirose, F., Osumi, T. (2008). Target Specificities of Estrogen Receptor-Related Receptors: Analysis of Binding Sequences and Identification of Rb1-Inducible Coiled-Coil 1 (Rb1cc1) as a Target Gene. J Biochem 143: 395-406 [Abstract] [Full Text]  
  • Zhou, D., Shen, R., Ye, J. J., Li, Y., Tsark, W., Isbell, D., Tso, P., Chen, S. (2008). Nuclear Receptor Coactivator PNRC2 Regulates Energy Expenditure and Adiposity. J. Biol. Chem. 283: 541-553 [Abstract] [Full Text]  
  • Fliegner, D., Westermann, D., Riad, A., Schubert, C., Becher, E., Fielitz, J., Tschope, C., Regitz-Zagrosek, V. (2008). Up-regulation of PPAR{gamma} in myocardial infarction. Eur J Heart Fail 10: 30-38 [Abstract] [Full Text]  
  • Wende, A. R., Schaeffer, P. J., Parker, G. J., Zechner, C., Han, D.-H., Chen, M. M., Hancock, C. R., Lehman, J. J., Huss, J. M., McClain, D. A., Holloszy, J. O., Kelly, D. P. (2007). A Role for the Transcriptional Coactivator PGC-1{alpha} in Muscle Refueling. J. Biol. Chem. 282: 36642-36651 [Abstract] [Full Text]  
  • Pieter de Lange, , Moreno, M., Silvestri, E., Lombardi, A., Goglia, F., Lanni, A. (2007). Fuel economy in food-deprived skeletal muscle: signaling pathways and regulatory mechanisms. FASEB J. 21: 3431-3441 [Abstract] [Full Text]  
  • Lanvin, O., Bianco, S., Kersual, N., Chalbos, D., Vanacker, J.-M. (2007). Potentiation of ICI182,780 (Fulvestrant)-induced Estrogen Receptor-{alpha} Degradation by the Estrogen Receptor-related Receptor-{alpha} Inverse Agonist XCT790. J. Biol. Chem. 282: 28328-28334 [Abstract] [Full Text]  
  • Sonoda, J., Laganiere, J., Mehl, I. R., Barish, G. D., Chong, L.-W., Li, X., Scheffler, I. E., Mock, D. C., Bataille, A. R., Robert, F., Lee, C.-H., Giguere, V., Evans, R. M. (2007). Nuclear receptor ERR{alpha} and coactivator PGC-1beta are effectors of IFN-{gamma}-induced host defense. Genes Dev. 21: 1909-1920 [Abstract] [Full Text]  
  • Spector, N. L., Yarden, Y., Smith, B., Lyass, L., Trusk, P., Pry, K., Hill, J. E., Xia, W., Seger, R., Bacus, S. S. (2007). Activation of AMP-activated protein kinase by human EGF receptor 2/EGF receptor tyrosine kinase inhibitor protects cardiac cells. Proc. Natl. Acad. Sci. USA 104: 10607-10612 [Abstract] [Full Text]  
  • Finck, B. N., Kelly, D. P. (2007). Peroxisome Proliferator-Activated Receptor {gamma} Coactivator-1 (PGC-1) Regulatory Cascade in Cardiac Physiology and Disease. Circulation 115: 2540-2548 [Full Text]  
  • Bonnelye, E., Zirngibl, R. A., Jurdic, P., Aubin, J. E. (2007). The Orphan Nuclear Estrogen Receptor-Related Receptor-{alpha} Regulates Cartilage Formation in Vitro: Implication of Sox9. Endocrinology 148: 1195-1205 [Abstract] [Full Text]  
  • Chen, E. I., Hewel, J., Krueger, J. S., Tiraby, C., Weber, M. R., Kralli, A., Becker, K., Yates, J. R. III, Felding-Habermann, B. (2007). Adaptation of Energy Metabolism in Breast Cancer Brain Metastases. Cancer Res. 67: 1472-1486 [Abstract] [Full Text]  
  • Pennacchio, L. A., Loots, G. G., Nobrega, M. A., Ovcharenko, I. (2007). Predicting tissue-specific enhancers in the human genome. Genome Res 17: 201-211 [Abstract] [Full Text]  
  • Villena, J. A., Hock, M. B., Chang, W. Y., Barcas, J. E., Giguere, V., Kralli, A. (2007). Orphan nuclear receptor estrogen-related receptor {alpha} is essential for adaptive thermogenesis. Proc. Natl. Acad. Sci. USA 104: 1418-1423 [Abstract] [Full Text]  
  • Finck, B. N. (2007). The PPAR regulatory system in cardiac physiology and disease. Cardiovasc Res 73: 269-277 [Abstract] [Full Text]  
  • Gaillard, S., Dwyer, M. A., McDonnell, D. P. (2007). Definition of the Molecular Basis for Estrogen Receptor-Related Receptor-{alpha}-Cofactor Interactions. Mol. Endocrinol. 21: 62-76 [Abstract] [Full Text]  
  • Zhang, Y., Ma, K., Sadana, P., Chowdhury, F., Gaillard, S., Wang, F., McDonnell, D. P., Unterman, T. G., Elam, M. B., Park, E. A. (2006). Estrogen-related Receptors Stimulate Pyruvate Dehydrogenase Kinase Isoform 4 Gene Expression. J. Biol. Chem. 281: 39897-39906 [Abstract] [Full Text]  
  • Michalik, L., Auwerx, J., Berger, J. P., Chatterjee, V. K., Glass, C. K., Gonzalez, F. J., Grimaldi, P. A., Kadowaki, T., Lazar, M. A., O'Rahilly, S., Palmer, C. N. A., Plutzky, J., Reddy, J. K., Spiegelman, B. M., Staels, B., Wahli, W. (2006). International Union of Pharmacology. LXI. Peroxisome Proliferator-Activated Receptors. Pharmacol. Rev. 58: 726-741 [Abstract] [Full Text]  
  • Stein, R A, McDonnell, D P (2006). Estrogen-related receptor {alpha} as a therapeutic target in cancer. Endocr Relat Cancer 13: S25-S32 [Abstract] [Full Text]  
  • Smith, A. G., Muscat, G. E. O. (2006). Orphan nuclear receptors: therapeutic opportunities in skeletal muscle. Am. J. Physiol. Cell Physiol. 291: C203-C217 [Abstract] [Full Text]  
  • Zhang, Z., Chen, K., Shih, J. C., Teng, C. T. (2006). Estrogen-Related Receptors-Stimulated Monoamine Oxidase B Promoter Activity Is Down-Regulated by Estrogen Receptors. Mol. Endocrinol. 20: 1547-1561 [Abstract] [Full Text]  
  • Hsieh, Y.-C., Choudhry, M. A., Yu, H.-P., Shimizu, T., Yang, S., Suzuki, T., Chen, J., Bland, K. I., Chaudry, I. H. (2006). Inhibition of cardiac PGC-1{alpha} expression abolishes ER{beta} agonist-mediated cardioprotection following trauma-hemorrhage. FASEB J. 20: 1109-1117 [Abstract] [Full Text]  
  • Barry, J. B., Laganiere, J., Giguere, V. (2006). A Single Nucleotide in an Estrogen-Related Receptor {alpha} Site Can Dictate Mode of Binding and Peroxisome Proliferator-Activated Receptor {gamma} Coactivator 1{alpha} Activation of Target Promoters. Mol. Endocrinol. 20: 302-310 [Abstract] [Full Text]  
  • Herzog, B., Cardenas, J., Hall, R. K., Villena, J. A., Budge, P. J., Giguere, V., Granner, D. K., Kralli, A. (2006). Estrogen-related Receptor {alpha} Is a Repressor of Phosphoenolpyruvate Carboxykinase Gene Transcription. J. Biol. Chem. 281: 99-106 [Abstract] [Full Text]  
  • Wende, A. R., Huss, J. M., Schaeffer, P. J., Giguere, V., Kelly, D. P. (2005). PGC-1{alpha} Coactivates PDK4 Gene Expression via the Orphan Nuclear Receptor ERR{alpha}: a Mechanism for Transcriptional Control of Muscle Glucose Metabolism. Mol. Cell. Biol. 25: 10684-10694 [Abstract] [Full Text]  
  • Stanley, W. C., Recchia, F. A., Lopaschuk, G. D. (2005). Myocardial Substrate Metabolism in the Normal and Failing Heart. Physiol. Rev. 85: 1093-1129 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»