| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on January 18, 2006
Accepted on February 23, 2006
gene transcription. An auto-regulatory loop controls PGC-1 expression in adipocytes via PPAR
co-activation
From Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain
* To whom correspondence should be addressed. E-mail: fvillarroya{at}ub.edu.
Thiazolidinediones (TZDs) are insulin-sensitizing drugs currently used to treat type II diabetes. They are activators of peroxisome proliferator-activated receptor-
(PPAR), and adipose tissue constitutes a major site for their biological effects. Peroxisome proliferator-activated receptor-coactivator-1
(PGC-1) is a transcriptional co-activator of PPAR and other transcription factors. It is involved in the control of mitochondrial biogenesis and its activity has been linked to insulin sensitization. Here we report that PGC-1 gene expression in brown and white adipocytes is a direct target of TZDs via PPAR activation. Activators of the retinoid-X receptor also induce PGC-1 gene expression. This is due to the presence of a PPAR-responsive element in the distal region of the PGC-1 gene promoter that binds PPAR/retinoid-X receptor heterodimers. Moreover, there is a positive auto-regulatory loop of control of the PGC-1 gene through co-activation of PPAR responsiveness to TZDs by PGC-1 itself. These data indicate that some of the effects of TZDs, especially promotion of mitochondrial biogenesis and oxidative pathways in adipose depots, entail PGC-1 up-regulation via enhanced transcription of the PGC-1 gene.
•
PPAR
This article has been cited by other articles:
 |
|
 |
|
  T. Coll, E. Eyre, R. Rodriguez-Calvo, X. Palomer, R. M. Sanchez, M. Merlos, J. C. Laguna, and M. Vazquez-Carrera Oleate Reverses Palmitate-induced Insulin Resistance and Inflammation in Skeletal Muscle Cells J. Biol. Chem., April 25, 2008; 283(17): 11107 - 11116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Hausman, S. P. Poulos, T. D. Pringle, and M. J. Azain The influence of thiazolidinediones on adipogenesis in vitro and in vivo: Potential modifiers of intramuscular adipose tissue deposition in meat animals J Anim Sci, April 1, 2008; 86(14_suppl): E236 - E243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Brodbeck, M. E. Balestra, A. M. Saunders, A. D. Roses, R. W. Mahley, and Y. Huang Rosiglitazone increases dendritic spine density and rescues spine loss caused by apolipoprotein E4 in primary cortical neurons PNAS, January 29, 2008; 105(4): 1343 - 1346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Bogacka, T. W. Gettys, L. de Jonge, T. Nguyen, J. M. Smith, H. Xie, F. Greenway, and S. R. Smith The Effect of {beta}-Adrenergic and Peroxisome Proliferator-Activated Receptor-{gamma} Stimulation on Target Genes Related to Lipid Metabolism in Human Subcutaneous Adipose Tissue Diabetes Care, May 1, 2007; 30(5): 1179 - 1186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schupp, J. C. Curtin, R. J. Kim, A. N. Billin, and M. A. Lazar A Widely Used Retinoic Acid Receptor Antagonist Induces Peroxisome Proliferator-Activated Receptor-{gamma} Activity Mol. Pharmacol., May 1, 2007; 71(5): 1251 - 1257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Chevillotte, M. Giralt, B. Miroux, D. Ricquier, and F. Villarroya Uncoupling Protein-2 Controls Adiponectin Gene Expression in Adipose Tissue Through the Modulation of Reactive Oxygen Species Production Diabetes, April 1, 2007; 56(4): 1042 - 1050. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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-{alpha}/PGC-1{alpha} Gene Regulatory Pathway Circulation, February 20, 2007; 115(7): 909 - 917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Handschin and B. M. Spiegelman Peroxisome Proliferator-Activated Receptor {gamma} Coactivator 1 Coactivators, Energy Homeostasis, and Metabolism Endocr. Rev., December 1, 2006; 27(7): 728 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Coll, M. Jove, R. Rodriguez-Calvo, E. Eyre, X. Palomer, R. M. Sanchez, M. Merlos, J. C. Laguna, and M. Vazquez-Carrera Palmitate-Mediated Downregulation of Peroxisome Proliferator-Activated Receptor-{gamma} Coactivator 1{alpha} in Skeletal Muscle Cells Involves MEK1/2 and Nuclear Factor-{kappa}B Activation. Diabetes, October 1, 2006; 55(10): 2779 - 2787. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
