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PPAR Research
Volume 2012, Article ID 483536, 9 pages
Research Article

Peroxisome Proliferator-Activated Receptor Agonists Differentially Regulate Inhibitor of DNA Binding Expression in Rodents and Human Cells

1Departmento de Biología, Facultades de Farmacia y Medicina, Universidad San Pablo-CEU, Urbanización Montepríncipe, Boadilla del Monte, 28668 Madrid, Spain
2Integrated Systems Toxicology Division, National Health and Environmental Effects Research Lab, US Environmental Protection Agency, 109 T.W. Alexander Drive, Research Triangle Park, NC 27711, USA
3Consulting Químico Sanitario (CQS) Laboratory, 28020 Madrid, Spain

Received 9 February 2012; Revised 2 April 2012; Accepted 4 April 2012

Academic Editor: Yuji Kamijo

Copyright © 2012 María del Carmen González 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.


Inhibitor of DNA binding (Id2) is a helix-loop-helix (HLH) transcription factor that participates in cell differentiation and proliferation. Id2 has been linked to the development of cardiovascular diseases since thiazolidinediones, antidiabetic agents and peroxisome proliferator-activated receptor (PPAR) gamma agonists, have been reported to diminish Id2 expression in human cells. We hypothesized that PPARα activators may also alter Id2 expression. Fenofibrate diminished hepatic Id2 expression in both late pregnant and unmated rats. In 24 hour fasted rats, Id2 expression was decreased under conditions known to activate PPARα. In order to determine whether the fibrate effects were mediated by PPARα, wild-type mice and PPARα-null mice were treated with Wy-14,643 (WY). WY reduced Id2 expression in wild-type mice without an effect in PPARα-null mice. In contrast, fenofibrate induced Id2 expression after 24 hours of treatment in human hepatocarcinoma cells (HepG2). MK-886, a PPARα antagonist, did not block fenofibrate-induced activation of Id2 expression, suggesting a PPARα-independent effect was involved. These findings confirm that Id2 is a gene responsive to PPARα agonists. Like other genes (apolipoprotein A-I, apolipoprotein A-V), the opposite directional transcriptional effect in rodents and a human cell line further emphasizes that PPARα agonists have different effects in rodents and humans.