PPAR Research The Molecular Basis of PPAR Function Guest Editors: Yaacov Barak and Chih-Hao Lee The Molecular Basis of PPAR Function PPAR Researsh The Molecular Basis of PPAR Function Guest Editors: Yaacov Barak and Chih-Hao Lee Copyright © 2010 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in volume 2010 of “PPAR Researsh.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editor-in-Chief Mostafa Z. Badr, University of Missouri-Kansas City, USA Advisory Editors Yaacov Barak, USA Jamal A. Ibdah, USA Michael K. Racke, USA Abdulbari B. Bener, UK Sander Kersten, The Netherlands J. K. Reddy, USA David Bishop-Bailey, UK James Klaunig, USA B. Staels, France George L. Blackburn, USA Beata Lecka-Czernik, USA T. J. Standiford, USA P. Chambon, France Christos S. Mantzoros, USA Ming-Jer Tsai, USA V. Chatterjee, UK Jorg¨ Mey, Germany John P. Vanden Heuvel, USA Salvatore Cuzzocrea, Italy Laszlo Nagy, Hungary Xian H. Wang, China J. M. Gimble, USA D. Piomelli, USA Jihan Youssef, USA Francine M. Gregoire, Singapore Associate Editors Josep Bassaganya-Riera, USA Weimin He, USA Elisabetta Mueller, USA Sandra Brunelleschi, Italy Jaou-Chen Huang, USA Marcelo H. Napimoga, Brazil Antonio Brunetti, Italy N. Ishida, Japan Dipak Panigrahy, USA Ching-Shih Chen, USA Fredrik Karpe, UK R. P. Phipps, USA Hyae Gyeong Cheon, Korea Shigeaki Kato, Japan Suofu Qin, USA Sharon Cresci, USA Ulrich Kintscher, Germany Michael E. Robbins, USA Michael L. Cunningham, USA Joshua K. Ko, China Ruth Roberts, UK Samir Deeb, USA Carolyn M. Komar, USA Lawrence Serfaty, France Batrice Desvergne, Switzerland Christopher Lau, USA Xu Shen, China Paul D. Drew, USA Chih-Hao Lee, USA Xing-Ming Shi, USA Klaus Eder, Germany Todd Leff,USA Alexander Staruschenko, USA Douglas L. Feinstein, USA Harry Martin, New Zealand Eiji Takeda, Japan Brian N. Finck, USA Anne Reifel Miller, USA Raghu Vemuganti, USA Pascal Froment, France Raghavendra G. Mirmira, USA Nanping Wang, China Howard P. Glauert, USA Hiroyuki Miyachi, Japan Barbour S. Warren, USA Youfei Guan, China Kiyoto Motojima, Japan Wei Xu, USA James P. Hardwick, USA Shaker A. Mousa, USA Tianxin Yang, USA Contents The Molecular Basis of PPAR Function, Yaacov Barak and Chih-Hao Lee Volume 2010, Article ID 510530, 2 pages Peroxisome Proliferator-Activated Receptor Alpha Target Genes, Maryam Rakhshandehroo, Bianca Knoch, Michael Muller,¨ and Sander Kersten Volume 2010, Article ID 612089, 20 pages Molecular Mechanisms and Genome-Wide Aspects of PPAR Subtype Specific Transactivation, Anne Bugge and Susanne Mandrup Volume 2010, Article ID 169506, 12 pages PPARG: Gene Expression Regulation and Next-Generation Sequencing for Unsolved Issues, Valerio Costa, Maria Assunta Gallo, Francesca Letizia, Marianna Aprile, Amelia Casamassimi, and Alfredo Ciccodicola Volume 2010, Article ID 409168, 17 pages Coordinate Transcriptomic and Metabolomic Effects of the Insulin Sensitizer Rosiglitazone on Fundamental Metabolic Pathways in Liver, Soleus Muscle, and Adipose Tissue in Diabetic db/db Mice, Sabrina Le Bouter, Marianne Rodriguez, Nolwen Guigal-Stephan, Sophie Courtade-Gaani, Laura Xuereb, Catherine de Montrion, Vincent Croixmarie, Thierry Umbdenstock, Claire Boursier-Neyret, Michel Lonchampt, Manuel Brun, Catherine Dacquet, Alain Ktorza, Brian-Paul Lockhart, and Jean-Pierre Galizzi Volume 2010, Article ID 679184, 17 pages Coactivators in PPAR-Regulated Gene Expression, Navin Viswakarma, Yuzhi Jia, Liang Bai, Aurore Vluggens, Jayme Borensztajn, Jianming Xu, and Janardan K. Reddy Volume 2010, Article ID 250126, 21 pages PRIC295, a Nuclear Receptor Coactivator, Identified from PPARα-Interacting Cofactor Complex, Sean R. Pyper, Navin Viswakarma, Yuzhi Jia, Yi-Jun Zhu, Joseph D. Fondell, and Janardan K. Reddy Volume 2010, Article ID 173907, 16 pages PPARs in Rhythmic Metabolic Regulation and Implications in Health and Disease, Purin Charoensuksai and Wei Xu Volume 2010, Article ID 243643, 9 pages PPARs: Nuclear Receptors Controlled by, and Controlling, Nutrient Handling through Nuclear and Cytosolic Signaling, Maria Moreno, Assunta Lombardi, Elena Silvestri, Rosalba Senese, Federica Cioffi, Fernando Goglia, Antonia Lanni, and Pieter de Lange Volume 2010, Article ID 435689, 10 pages PPAR-γ Signaling Crosstalk in Mesenchymal Stem Cells, Ichiro Takada, Alexander P. Kouzmenko, and Shigeaki Kato Volume 2010, Article ID 341671, 6 pages Hindawi Publishing Corporation PPAR Research Volume 2010, Article ID 510530, 2 pages doi:10.1155/2010/510530 Editorial The Molecular Basis of PPAR Function Yaacov Barak1 and Chih-Hao Lee2 1 Magee-Womens Research Institute, Department of OBGYN and Reproductive Sciences, University of Pittsburgh, 204 Craft Avenue, Pittsburgh, PA 15213, USA 2 Department of Genetics and Complex Diseases, Harvard University School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA Correspondence should be addressed to Yaacov Barak, [email protected] Received 31 December 2010; Accepted 31 December 2010 Copyright © 2010 Y. Barak and C.-H. Lee. 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. Over the past four and a half years, fifteen issues of PPAR third review, Costa et al. discuss population-wide sequence Research have been published and an additional five are variations of PPARγ and their potential impact on target currently in various phases of production. Collectively, gene expression, and review the application of massive these issues have covered a large array of physiological parallel sequencing for the identification of PPARγ cistromes functions of PPARs in health and disease, including their (the collection of genomic sequences bound by PPARγ) functions in diverse cell and tissue types, their roles in a and transcriptomes. In the second section of this issue, the host of clinical conditions, and their rich pharmaceutical research article by Le Bouter et al. analyzes gene expression potential. Yet, one crucial overarching selection seems to have changes in adipose tissue, liver, and muscle of leptin receptor escaped attention amid this exciting variety—the fundamen- deficient diabetic obese mice treated with the PPARγ agonist tal molecular mechanisms that underlie PPAR action. PPARs and insulin sensitizer rosiglitazone, in order to establish the are first and foremost transcription factors that execute molecular basis of its therapeutic physiological effects. intricate regulation of gene networks, and are in turn subject Two papers by Viswakarma et al. and Pyper et al., one to complex fine-tuning and control. Inevitably, thorough a review and the other a research manuscript, concern understanding of their cellular and organismal functions transcription cofactors of PPARs. Their thorough review and full capitalization on their pharmaceutical power require summarizes no less than twelve types of PPAR coactivators, detailed understanding of these molecular underpinnings. which, ironically, do not account for the fullest gamut of While the list of potential subplots is far too long to fit known PPAR coactivators. Nothing is better to illustrate into a single issue, the current issue has begun to fill this the complexity of this ever-growing subplot than this coverage gap. Three review articles and one research group’s accompanying research article, which describes the manuscript tackle the subject of PPAR target genes. First identification and initial characterization of yet a new PPAR is a comprehensive review of PPARα target genes by coactivator, a subunit of the mediator complex termed Rakhshandehroo et al. Although the primary focus of their PRIC295. review is hepatic targets, many of the discussed features are In the course of executing their physiological roles, applicable to the physiology of PPARα in other tissues. Next, PPARs are both regulated by and intersect with diverse Bugge and Mandrup review two complementary aspects signaling pathways. Three review articles touch on three of of PPARγ-regulated genes. The first concerns the role of these many types of interactions. Charoensuksai and Xu the N-terminal ligand-independent activation domain, also review the effects of circadian signaling on the expression and known as the A/B or AF-1 domain, in determining PPAR activities of PPARs, Moreno et al. summarize the interactions subtype specificity and in modulating target activation between nutrient signaling and PPARs, whereas Takada in adipocytes. The second focuses on recent insights into et al. expand on the interaction of PPARγ with downstream genomewide PPARγ actions in adipocytes and macrophages effectors of cytokine and Wnt signaling in mesenchymal stem gained from chromatin immunoprecipitation studies. In the cells. 2 PPAR Research While this volume is a solid start, it did not go the full distance and many of the molecular bases of PPAR function remain to be reviewed. Some topics, such as the structure- function relationships of PPARs or their posttranslational regulation won no coverage in this issue. Among the touched upon topics, some additional reviews are crucial for rounding out the coverage, such as target genes of PPARβ/δ or additional signaling crosstalk of PPARs. And so, it would be great to see a fresh team of guest editors pick the topic up where we