Table of Contents Author Guidelines Submit a Manuscript
PPAR Research
Volume 2007, Article ID 32696, 7 pages
http://dx.doi.org/10.1155/2007/32696
Review Article

Selective Modulators of PPAR-γ Activity: Molecular Aspects Related to Obesity and Side-Effects

Department of Biology, Metabolex Inc., 3876 Bay Center Place, Hayward 94545, CA, USA

Received 3 October 2006; Revised 21 November 2006; Accepted 22 November 2006

Academic Editor: Sander Kersten

Copyright © 2007 Fang Zhang 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.

Citations to this Article [90 citations]

The following is the list of published articles that have cited the current article.

  • Ondřej Šeda, and Lucie Šedova, “Peroxisome proliferator-activated receptors as molecular targets in relation to obesity and type 2 diabetes,” Pharmacogenomics, vol. 8, no. 6, pp. 587–596, 2007. View at Publisher · View at Google Scholar
  • Barbara Gross, and Bart Staels, “PPAR agonists: multimodal drugs for the treatment of type-2 diabetes,” Best Practice & Research Clinical Endocrinology & Metabolism, vol. 21, no. 4, pp. 687–710, 2007. View at Publisher · View at Google Scholar
  • Claude Roberge, André C. Carpentier, Marie-France Langlois, Jean-Patrice Baillargeon, Jean-Luc Ardilouze, Pierre Maheux, and Nicole Gallo-Payet, “Adrenocortical dysregulation as a major player in insulin resistance and onset of obesity,” American Journal of Physiology - Endocrinology and Metabolism, vol. 293, no. 6, pp. E1465–E1478, 2007. View at Publisher · View at Google Scholar
  • Ken Sugimoto, Ludmila Kazdová, Nathan R. Qi, Masaya Hyakukoku, Vladimír Křen, Miroslava Šimáková, Václav Zídek, Theodore W. Kurtz, and Michal Pravenec, “Telmisartan increases fatty acid oxidation in skeletal muscle through a peroxisome proliferator-activated receptor-γ dependent pathway,” Journal of Hypertension, vol. 26, no. 6, pp. 1209–1215, 2008. View at Publisher · View at Google Scholar
  • Richard H. Moseley, “Therapy for nonalcoholic fatty liver disease,” Journal of Clinical Gastroenterology, vol. 42, no. 4, pp. 332–335, 2008. View at Publisher · View at Google Scholar
  • Linda M. Sanderson, Philip J. de Groot, Guido J.E.J. Hooiveld, Arjen Koppen, Eric Kalkhoven, Michael Müller, and Sander Kersten, “Effect of synthetic dietary triglycerides: A novel research paradigm for nutrigenomics,” PLoS ONE, vol. 3, no. 2, 2008. View at Publisher · View at Google Scholar
  • Oliver Rau, Heiko Zettl, Laura Popescu, Dieter Steinhilber, and Manfred Schubert-Zsilavecz, “The treatment of dyslipidemia - What's left in the pipeline?,” Chemmedchem, vol. 3, no. 2, pp. 206–221, 2008. View at Publisher · View at Google Scholar
  • Monika Mueller, Brigitte Lukas, Johannes Novak, Tommaso Simoncini, Andrea Riccardo Genazzani, and Alois Jungbauer, “Oregano: A source for peroxisome proliferator-activated receptor γ antagonists,” Journal of Agricultural and Food Chemistry, vol. 56, no. 24, pp. 11621–11630, 2008. View at Publisher · View at Google Scholar
  • Jennifer M. Wilkinson, Steven Hayes, David Thompson, Pamela Whitney, and Kun Bi, “Compound profiling using a panel of steroid hormone receptor cell-based assays,” Journal of Biomolecular Screening, vol. 13, no. 8, pp. 755–765, 2008. View at Publisher · View at Google Scholar
  • Harrihar A. Pershadsingh, and David M. Moore, “PPARγ Agonists: Potential as Therapeutics for Neovascular Retinopathies,” PPAR Research, vol. 2008, pp. 1–13, 2008. View at Publisher · View at Google Scholar
  • Holly J. Clarke, Francine Gregoire, Fang Ma, Robert Martin, Spring Zhao, and Brian E. Lavan, “Cross-Species Differential Plasma Protein Binding of MBX-102/JNJ39659100: A Novel PPAR-γ Agonist,” PPAR Research, vol. 2008, pp. 1–10, 2008. View at Publisher · View at Google Scholar
  • Min-Chul Cho, Kyoung Lee, Sang-Gi Paik, and Do-Young Yoon, “Peroxisome Proliferators-Activated Receptor (PPAR) Modulators and Metabolic Disorders,” PPAR Research, vol. 2008, pp. 1–14, 2008. View at Publisher · View at Google Scholar
  • Katherine L. Schaefer, “PPARγ Inhibitors as Novel Tubulin-Targeting Agents,” PPAR Research, vol. 2008, pp. 1–9, 2008. View at Publisher · View at Google Scholar
  • Tatiana M. Garcia-Bates, Geniece M. Lehmann, Patricia J. Simpson-Haidaris, Steven H. Bernstein, Patricia J. Sime, and Richard P. Phipps, “Role of Peroxisome Proliferator-Activated Receptor Gamma and Its Ligands in the Treatment of Hematological Malignancies,” PPAR Research, vol. 2008, pp. 1–18, 2008. View at Publisher · View at Google Scholar
  • G. M. Lehmann, T. M. Garcia-Bates, T. J. Smith, S. E. Feldon, and R. P. Phipps, “Regulation of Lymphocyte Function by PPARγ: Relevance to Thyroid Eye Disease-Related Inflammation,” PPAR Research, vol. 2008, pp. 1–12, 2008. View at Publisher · View at Google Scholar
  • Linda S. Higgins, and Christos S. Mantzoros, “The Development of INT131 as a Selective PPARγ Modulator: Approach to a Safer Insulin Sensitizer,” PPAR Research, vol. 2008, pp. 1–9, 2008. View at Publisher · View at Google Scholar
  • Nobuo Cho, and Yu Momose, “Peroxisome proliferator-activated receptor γ agonists as insulin sensitizers: From the discovery to recent progress,” Current Topics in Medicinal Chemistry, vol. 8, no. 17, pp. 1483–1507, 2008. View at Publisher · View at Google Scholar
  • Tom Hsun-Wei Huang, Aik Wei Teoh, Bei-Lun Lin, Diana Shu-Hsuan Lin, and Basil Roufogalis, “The role of herbal PPAR modulators in the treatment of cardiometabolic syndrome,” Pharmacological Research, vol. 60, no. 3, pp. 195–206, 2009. View at Publisher · View at Google Scholar
  • Francine M. Gregoire, Fang Zhang, Holly J. Clarke, Thomas A. Gustafson, Dorothy D. Sears, Svetlana Favelyukis, James Lenhard, Dennis Rentzeperis, L. Edward Clemens, Yi Mu, and Brian E. Lavan, “MBX-102/JNJ39659100, a Novel Peroxisome Proliferator-Activated Receptor-Ligand with Weak Transactivation Activity Retains Antidiabetic Properties in the Absence of Weight Gain and Edema,” Molecular Endocrinology, vol. 23, no. 7, pp. 975–988, 2009. View at Publisher · View at Google Scholar
  • Tristano Pancani, Jeremiah T. Phelps, James L. Searcy, Michael W. Kilgore, Kuey-Chu Chen, Nada M. Porter, and Olivier Thibault, “Distinct modulation of voltage-gated and ligand-gated Ca2+ currents by PPAR-gamma agonists in cultured hippocampal neurons,” Journal Of Neurochemistry, vol. 109, no. 6, pp. 1800–1811, 2009. View at Publisher · View at Google Scholar
  • Terri L. Levien, and Danial E. Baker, “New drugs in development for the treatment of diabetes,” Diabetes Spectrum, vol. 22, no. 2, pp. 92–106, 2009. View at Publisher · View at Google Scholar
  • Luis Villacorta, Francisco J. Schopfer, Jifeng Zhang, Bruce A. Freeman, and Y. Eugene Chen, “PPARγ and its ligands: Therapeutic implications in cardiovascular disease,” Clinical Science, vol. 116, no. 3, pp. 205–218, 2009. View at Publisher · View at Google Scholar
  • Monika Mueller, and Alois Jungbauer, “Culinary plants, herbs and spices - A rich source of PPAR gamma ligands,” Food Chemistry, vol. 117, no. 4, pp. 660–667, 2009. View at Publisher · View at Google Scholar
  • Michael L. Mohler, Yali He, Zhongzhi Wu, Dong Jin Hwang, and Duane D. Miller, “Recent and Emerging Anti-Diabetes Targets,” Medicinal Research Reviews, vol. 29, no. 1, pp. 125–195, 2009. View at Publisher · View at Google Scholar
  • Apurva Chandalia, Holly J. Clarke, L. Edward Clemens, Bindu Pandey, Vic Vicena, Paul Lee, Brian E. Lavan, and Francine M. Gregoire, “MBX-102/JNJ39659100, a Novel Non-TZD Selective Partial PPAR-γ Agonist Lowers Triglyceride Independently of PPAR-α Activation,” PPAR Research, vol. 2009, pp. 1–12, 2009. View at Publisher · View at Google Scholar
  • Arjen Koppen, Rene Houtman, Dirk Pijnenburg, Ellen H. Jeninga, Rob Ruijtenbeek, and Eric Kalkhoven, “Nuclear receptor-coregulator interaction profiling identifies TRIP3 as a novel peroxisome proliferator-activated receptor γ cofactor,” Molecular and Cellular Proteomics, vol. 8, no. 10, pp. 2212–2226, 2009. View at Publisher · View at Google Scholar
  • Francisco J. Schopfer, Marsha P. Cole, Alison L. Groeger, Chen-Shan Chen, Nicholas K. H. Khoo, Steven R. Woodcock, Franca Golin-Bisello, U. Nkiru Motanya, Yong Li, Jifeng Zhang, Minerva T. Garcia-Barrio, Tanja K. Rudolph, Volker Rudolph, Gustavo Bonacci, Paul R. S. Baker, H. Eric Xu, Carlos I. Batthyany, Y. Eugene Chen, Tina M. Hallis, and Bruce A. Freeman, “Covalent Peroxisome Proliferator-activated Receptor gamma Adduction by Nitro-fatty Acids SELECTIVE LIGAND ACTIVITY AND ANTI-DIABETIC SIGNALING ACTIONS,” Journal Of Biological Chemistry, vol. 285, no. 16, pp. 12321–12333, 2010. View at Publisher · View at Google Scholar
  • Lalit S Doshi, Manoja Kumar Brahma, Umakant A Bahirat, Amol V Dixit, and Kumar VS Nemmani, “Discovery and development of selective PPARγ modulators as safe and effective antidiabetic agents,” Expert Opinion on Investigational Drugs, vol. 19, no. 4, pp. 489–512, 2010. View at Publisher · View at Google Scholar
  • Jiwon Choi, Yunsun Park, Hui Sun Lee, Young Yang, and Sukjoon Yoon, “1,3-Diphenyl-1H-pyrazole derivatives as a new series of potent PPARγ partial agonists,” Bioorganic & Medicinal Chemistry, vol. 18, no. 23, pp. 8315–8323, 2010. View at Publisher · View at Google Scholar
  • George L. Blackburn, “From bench to bedside: novel mechanisms and therapeutic advances through the development of selective peroxisome proliferator-activated receptor gamma modulators,” American Journal Of Clinical Nutrition, vol. 91, no. 1, pp. 251S–253S, 2010. View at Publisher · View at Google Scholar
  • Linda Slanec Higgins, and Alex M. DePaoli, “Selective peroxisome proliferator-activated receptor gamma (PPAR gamma) modulation as a strategy for safer therapeutic PPAR gamma activation,” American Journal Of Clinical Nutrition, vol. 91, no. 1, pp. 267S–272S, 2010. View at Publisher · View at Google Scholar
  • Jihan Youssef, and Mostafa Badr, “Peroxisome proliferator-activated receptors and cancer: challenges and opportunities,” British Journal Of Pharmacology, vol. 164, no. 1, pp. 68–82, 2011. View at Publisher · View at Google Scholar
  • Jonathan P. Whitehead, “Diabetes: New conductors for the peroxisome proliferator-activated receptor gamma (PPAR gamma) orchestra,” International Journal Of Biochemistry & Cell Biology, vol. 43, no. 8, pp. 1071–1074, 2011. View at Publisher · View at Google Scholar
  • Faine, Rudnicki, César, Heras, Boscá, Souza, Hernandes, Galdino, Lima, Pitta, and Abdalla, “Anti-inflammatory and antioxidant properties of a new arylidene- thiazolidinedione in macrophages,” Current Medicinal Chemistry, vol. 18, no. 22, pp. 3351–3360, 2011. View at Publisher · View at Google Scholar
  • Vagner, and Santigosa, “Characterization and modulation of gene expression and enzymatic activity of delta-6 desaturase in teleosts: A review,” Aquaculture, vol. 315, no. 1-2, pp. 131–143, 2011. View at Publisher · View at Google Scholar
  • Fredrick L. Dunn, Linda S. Higgins, Jill Fredrickson, and Alex M. DePaoli, “Selective modulation of PPAR gamma activity can lower plasma glucose without typical thiazolidinedione side-effects in patients with Type 2 diabetes,” Journal Of Diabetes And Its Complications, vol. 25, no. 3, pp. 151–158, 2011. View at Publisher · View at Google Scholar
  • Yoko Endo, Masashi Suzuki, Hideomi Yamada, Shoko Horita, Motoei Kunimi, Osamu Yamazaki, Ayumi Shirai, Motonobu Nakamura, Naoyuki Iso-O, Yuehong Li, Masumi Hara, Kazuhisa Tsukamoto, Nobuo Moriyama, Akihiko Kudo, Hayato Kawakami, Toshimasa Yamauchi, Naoto Kubota, Takashi Kadowaki, Haruki Kume, Yutaka Enomoto, Yukio Homma, George Seki, and Toshiro Fujita, “Thiazolidinediones Enhance Sodium-Coupled Bicarbonate Absorption from Renal Proximal Tubules via PPARγ-Dependent Nongenomic Signaling,” Cell Metabolism, vol. 13, no. 5, pp. 550–561, 2011. View at Publisher · View at Google Scholar
  • Gerard A. Rodrigues, Florence Maurier-Mahe, Dixie-Lee Shurland, Anne Mclaughlin, Keith Luhrs, Emeline Throo, Laurence Delalonde-Delaunay, Diego Pallares, Fabien Schweighoffer, and John Donello, “Differential Effects of PPAR gamma Ligands on Oxidative Stress-Induced Death of Retinal Pigmented Epithelial Cells,” Investigative Ophthalmology & Visual Science, vol. 52, no. 2, pp. 890–903, 2011. View at Publisher · View at Google Scholar
  • Alessandro Antonelli, Silvia Martina Ferrari, Poupak Fallahi, Simona Piaggi, Aldo Paolicchi, Stefano Sellari Franceschini, Mario Salvi, and Ele Ferrannini, “Cytokines (interferon-γ and tumor necrosis factor–α)-induced nuclear factor–κB activation and chemokine (C-X-C motif) ligand 10 release in Graves disease and ophthalmopathy are modulated by pioglitazone,” Metabolism, vol. 60, no. 2, pp. 277–283, 2011. View at Publisher · View at Google Scholar
  • Min-Chul Cho, Dong-Hun Lee, Eun Jin Kim, Jee-young Lee, Jeong-Woo Kang, Jong Hwan Song, Youhoon Chong, Yangmi Kim, Jin-Tae Hong, and Do-Young Yoon, “Novel PPAR gamma partial agonists with weak activity and no cytotoxicity; identified by a simple PPAR gamma ligand screening system,” Molecular And Cellular Biochemistry, vol. 358, no. 1-2, pp. 75–83, 2011. View at Publisher · View at Google Scholar
  • Tsuyoshi Goto, Young-Il Kim, Kozue Funakoshi, Aki Teraminami, Taku Uemura, Shizuka Hirai, Joo-Young Lee, Makoto Makishima, Rieko Nakata, Hiroyasu Inoue, Hiroyuki Senju, Masayoshi Matsunaga, Fumihiko Horio, Nobuyuki Takahashi, and Teruo Kawada, “Farnesol, an isoprenoid, improves metabolic abnormalities in mice via both PPAR alpha-dependent and -independent pathways,” American Journal Of Physiology-Endocrinology And Metabolism, vol. 301, no. 5, pp. E1022–E1032, 2011. View at Publisher · View at Google Scholar
  • Mi-Kyung Kim, Yu Na Chae, Song-hyen Choi, Ho Sang Moon, Moon-Ho Son, Myung-Ho Bae, Hyun-ho Choi, Youn Hur, Eunkyung Kim, Yoo Hoi Park, Chan Sun Park, Jae Gyu Kim, Joong In Lim, and Chang Yell Shin, “PAM-1616, a selective peroxisome proliferator-activated receptor γ modulator with preserved anti-diabetic efficacy and reduced adverse effects,” European Journal of Pharmacology, vol. 650, no. 2-3, pp. 673–681, 2011. View at Publisher · View at Google Scholar
  • Shanika P. Samarasinghe, Maria M. Sutanto, Arpad M. Danos, Daniel N. Johnson, Matthew J. Brady, and Ronald N. Cohen, “Altering PPARγ Ligand Selectivity Impairs Adipogenesis by Thiazolidinediones But Not Hormonal Inducers,” Obesity, vol. 17, no. 5, pp. 965–972, 2012. View at Publisher · View at Google Scholar
  • Makoto Inoue, Hiroki Tanabe, Akira Matsumoto, Michiyo Takagi, Keizo Umegaki, Sakae Amagaya, and Jiro Takahashi, “Astaxanthin functions differently as a selective peroxisome proliferator-activated receptor γ modulator in adipocytes and macrophages,” Biochemical Pharmacology, vol. 84, no. 5, pp. 692–700, 2012. View at Publisher · View at Google Scholar
  • Yejun Tan, Eric S. Muise, Hongyue Dai, Richard Raubertas, Kenny K. Wong, G. Marie Thompson, Harold B. Wood, Peter T. Meinke, Pek Yee Lum, John R. Thompson, and Joel P. Berger, “Novel Transcriptome Profiling Analyses Demonstrate that Selective Peroxisome Proliferator-Activated Receptor gamma (PPAR gamma) Modulators Display Attenuated and Selective Gene Regulatory Activity in Comparison with PPAR gamma Full Agonists,” Molecular Pharmacology, vol. 82, no. 1, pp. 68–79, 2012. View at Publisher · View at Google Scholar
  • Der-Rong Din, and Jhong-Yan Jiang, “Delay-constrained survivable multicast routing problem in WDM networks,” Computer Communications, vol. 35, no. 10, pp. 1172–1184, 2012. View at Publisher · View at Google Scholar
  • Agrawal, Jain, and Dikshit, “Balaglitazone: A second generation peroxisome proliferator-activated receptor (PPAR) gamma (γ) agonist,” Mini-Reviews in Medicinal Chemistry, vol. 12, no. 2, pp. 87–97, 2012. View at Publisher · View at Google Scholar
  • Pratima Jain, Subodh N. Dikshit, and Ritesh Agrawal, “Ligand-based pharmacophore detection and screening of potential Glitazones,” Current Enzyme Inhibition, vol. 8, no. 1, pp. 22–46, 2012. View at Publisher · View at Google Scholar
  • Meera Penumetcha, and Nalini Santanam, “Nutraceuticals as Ligands of PPARγ,” PPAR Research, vol. 2012, pp. 1–7, 2012. View at Publisher · View at Google Scholar
  • Angélica Amorim Amato, and Francisco de Assis Rocha Neves, “Idealized PPARγ-Based Therapies: Lessons from Bench and Bedside,” PPAR Research, vol. 2012, pp. 1–9, 2012. View at Publisher · View at Google Scholar
  • Ning Zhang, Wei Chen, Xinbo Zhou, Xiaolin Zhou, Xinni Xie, Aimin Meng, Song Li, and Lili Wang, “C333H ameliorated insulin resistance through selectively modulating peroxisome proliferator-activated receptor γ in brown adipose tissue of db/db mice,” Biological and Pharmaceutical Bulletin, vol. 36, no. 6, pp. 980–987, 2013. View at Publisher · View at Google Scholar
  • Li-Li Shi, Chu-Bing Tan, and Zhi-Xing Zhou, “Advances in PPARY-related drug research,” Chinese Pharmaceutical Journal, vol. 48, no. 6, pp. 406–409, 2013. View at Publisher · View at Google Scholar
  • David F. Lehmann, and Braj B. Lohray, “A Lesson in Moderation: Applying Pharmacodynamics to Clarify the Relationship Between Thiazolidinediones and Adverse Vascular Outcomes in Type 2 Diabetes,” The Journal of Clinical Pharmacology, vol. 48, no. 8, pp. 999–1002, 2013. View at Publisher · View at Google Scholar
  • Joshua P. Taygerly, Lawrence R. McGee, Steven M. Rubenstein, Jonathan B. Houze, Timothy D. Cushing, Yang Li, Alykhan Motani, Jin-Long Chen, Walter Frankmoelle, Guosen Ye, Marc R. Learned, Juan Jaen, Shichang Miao, Pieter B. Timmermans, Martin Thoolen, Patrick Kearney, John Flygare, Holger Beckmann, Jennifer Weiszmann, Michelle Lindstrom, Nigel Walker, Jinsong Liu, Donna Biermann, Zhulun Wang, Atsushi Hagiwara, Tetsuya Iida, Hisateru Aramaki, Yuki Kitao, Hisashi Shinkai, Noboru Furukawa, Jun Nishiu, and Motonao Nakamura, “Discovery of INT131: A selective PPARγ modulator that enhances insulin sensitivity,” Bioorganic & Medicinal Chemistry, vol. 21, no. 4, pp. 979–992, 2013. View at Publisher · View at Google Scholar
  • Jihan A. Youssef, and Mostafa Z. Badrpp. 1–137, 2013. View at Publisher · View at Google Scholar
  • W. Zheng, X. Feng, L. Qiu, Z. Pan, R. Wang, S. Lin, D. Hou, L. Jin, and Y. Li, “Identification of the antibiotic ionomycin as an unexpected peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand with a unique binding mode and effective glucose-lowering activity in a mouse model of diabetes,” Diabetologia, vol. 56, no. 2, pp. 401–411, 2013. View at Publisher · View at Google Scholar
  • Antonietta Bernardo, Roberta De Simone, Chiara De Nuccio, Sergio Visentin, and Luisa Minghetti, “The nuclear receptor peroxisome proliferator-activated receptor-gamma promotes oligodendrocyte differentiation through mechanisms involving mitochondria and oscillatory Ca2+ waves,” Biological Chemistry, vol. 394, no. 12, pp. 1607–1614, 2013. View at Publisher · View at Google Scholar
  • B. Metidji, and B. Mendil, “New Neural Power System Stabilizer for Brushless Exciter,” Arabian Journal for Science and Engineering, vol. 38, no. 11, pp. 3103–3112, 2013. View at Publisher · View at Google Scholar
  • Wenting Xiong, Li Gu, Chao Wang, Hongxia Sun, and Xin Liu, “Anti-hyperglycemic and hypolipidemic effects of Cistanche tubulosa in type 2 diabetic db/db mice,” Journal of Ethnopharmacology, 2013. View at Publisher · View at Google Scholar
  • Praveen Thaggikuppe Krishnamurthy, Moola Joghee Nanjan Chandrasekar, and Moola Joghee Nanjan, “Newer approaches to the discovery of glitazones,” Mini-Reviews in Organic Chemistry, vol. 10, no. 1, pp. 66–72, 2013. View at Publisher · View at Google Scholar
  • Barna Peitl, Laszlo Drimba, Peter Hari, Andras Malnasi-Csizmadia, Jozsef Nemeth, Zoltan Szilvassy, Diana Kovacs, Zoltan Simon, Csaba Hegedus, and Reka Sari, “Identification of PPAR gamma ligands with One-dimensional Drug Profile Matching,” Drug Design Development And Therapy, vol. 7, pp. 917–928, 2013. View at Publisher · View at Google Scholar
  • Sun-Sil Choi, Eun Sun Kim, Minseob Koh, Soo-Jin Lee, Donghyun Lim, Yong Ryoul Yang, Hyun-Jun Jang, Kyung-ah Seo, Sang-Hyun Min, In Hee Lee, Seung Bum Park, Pann-Ghill Suh, and Jang Hyun Choi, “A Novel Non-agonist Peroxisome Proliferator-activated Receptor gamma (PPAR gamma) Ligand UHC1 Blocks PPAR gamma Phosphorylation by Cyclin-dependent Kinase 5 (CDK5) and Improves Insulin Sensitivity,” Journal of Biological Chemistry, vol. 289, no. 38, pp. 26618–26629, 2014. View at Publisher · View at Google Scholar
  • Alex M. DePaoli, Linda S. Higgins, Robert R. Henry, Christos Mantzoros, and Fredrick L. Dunn, “Can a Selective PPAR gamma Modulator Improve Glycemic Control in Patients With Type 2 Diabetes With Fewer Side Effects Compared With Pioglitazone?,” Diabetes Care, vol. 37, no. 7, pp. 1918–1923, 2014. View at Publisher · View at Google Scholar
  • Shashidhara M. Kotian, and K. N. Shubhanga, “Performance of Synchronous Machine Models in a Series-Capacitor Compensated System,” Ieee Transactions on Power Systems, vol. 29, no. 3, pp. 1023–1032, 2014. View at Publisher · View at Google Scholar
  • Matthew B. Wright, Michele Bortolini, Moh Tadayyon, and Martin Bopst, “Minireview: Challenges and Opportunities in Development of PPAR Agonists,” Molecular Endocrinology, vol. 28, no. 11, pp. 1756–1768, 2014. View at Publisher · View at Google Scholar
  • Charlotte Andersen, Dorota Kotowska, Christian G. Tortzen, Karsten Kristiansen, John Nielsen, and Rasmus Koefoed Petersen, “2-(2-Bromophenyl)-formononetin and 2-heptyl-formononetin are PPAR gamma partial agonists and reduce lipid accumulation in 3T3-L1 adipocytes,” Bioorganic & Medicinal Chemistry, vol. 22, no. 21, pp. 6105–6111, 2014. View at Publisher · View at Google Scholar
  • Chunyan Yang, Qianrong Li, and Yong Li, “Targeting Nuclear Receptors with Marine Natural Products,” Marine Drugs, vol. 12, no. 2, pp. 601–635, 2014. View at Publisher · View at Google Scholar
  • Josep A. Villena, and Mònica Zamora, “Targeting mitochondrial biogenesis to treat insulin resistance,” Current Pharmaceutical Design, vol. 20, no. 35, pp. 5527–5557, 2014. View at Publisher · View at Google Scholar
  • Mahmoud Mansour, “The Roles of Peroxisome Proliferator-Activated Receptors in the Metabolic Syndrome,” Glucose Homeostatis and the Pathogenesis of Diabetes Mellitus, vol. 121, pp. 217–266, 2014. View at Publisher · View at Google Scholar
  • T. Goto, R. Nakayama, M. Yamanaka, M. Takata, T. Takazawa, K. Watanabe, K. Maruta, R. Nagata, J. Nagamine, A. Tsuchida, and H. Kato, “Effects of DSP-8658, a Novel Selective Peroxisome Proliferator-activated Receptors a/gamma Modulator, on Adipogenesis and Glucose Metabolism in Diabet,” Experimental And Clinical Endocrinology & Diabetes, vol. 123, no. 8, pp. 492–499, 2015. View at Publisher · View at Google Scholar
  • Alice Asteian, Anne-Laure Blayo, Yuanjun He, Marcel Koenig, Youseung Shin, Dana S. Kuruvilla, Cesar A. Corzo, Michael D. Cameron, Li Lin, Claudia Ruiz, Susan Khan, Naresh Kumar, Scott Busby, David P. Marciano, Ruben D. Garcia-Ordonez, Patrick R. Griffin, and Theodore M. Kamenecka, “Design, Synthesis, and Biological Evaluation of Indole Biphenylcarboxylic Acids as PPARγ Antagonists,” ACS Medicinal Chemistry Letters, pp. 150805134321008, 2015. View at Publisher · View at Google Scholar
  • Shane M. Regnier, Essam El-Hashani, Wakanene Kamau, Xiaojie Zhang, Nicole L. Massad, and Robert M. Sargis, “Tributyltin differentially promotes development of a phenotypically distinct adipocyte,” Obesity, 2015. View at Publisher · View at Google Scholar
  • Chang Liu, Tingting Feng, Ningyu Zhu, Peng Liu, Xiaowan Han, Minghua Chen, Xiao Wang, Ni Li, Yongzhen Li, Yanni Xu, and Shuyi Si, “Identification of a novel selective agonist of PPARγ with no promotion of adipogenesis and less inhibition of osteoblastogenesis,” Scientific Reports, vol. 5, pp. 9530, 2015. View at Publisher · View at Google Scholar
  • Ren Wang, Lihua Dai, and Jinjin Chen, “Identification of a proliferator-activated receptor-gamma antagonist for the treatment of type 2 diabetes mellitus,” Experimental And Therapeutic Medicine, vol. 9, no. 2, pp. 446–450, 2015. View at Publisher · View at Google Scholar
  • Jihan Youssef, and Mostafa Badr, “Peroxisome Proliferator-Activated Receptors Features, Functions, and Future,” Nuclear Receptor Research, vol. 2, 2015. View at Publisher · View at Google Scholar
  • Alice J. Kroker, and John B. Bruning, “ Review of the Structural and Dynamic Mechanisms of PPAR γ Partial Agonism ,” PPAR Research, vol. 2015, pp. 1–15, 2015. View at Publisher · View at Google Scholar
  • Jun Zhang, Xin Liu, Xian-Bin Xie, Xian-Chao Cheng, and Run-Ling Wang, “Multitargeted bioactive ligands for PPARs discovered in the last decade,” Chemical Biology & Drug Design, 2016. View at Publisher · View at Google Scholar
  • Juan Carlos Corona, and Michael R. Duchen, “PPARγ as a therapeutic target to rescue mitochondrial function in neurological disease,” Free Radical Biology and Medicine, 2016. View at Publisher · View at Google Scholar
  • Jina Kim, Yu-Jin Lee, Jung Min Kim, Dong Cho Han, So Young Lee, Myung-Ae Bae, Jin Hee Ahn, and Byoung-Mog Kwon, “PPARγ agonists induce adipocyte differentiation by modulating the expression of Lipin-1, which acts as a PPARγ phosphatase,” International Journal of Biochemistry and Cell Biology, vol. 81, pp. 57–66, 2016. View at Publisher · View at Google Scholar
  • Arunoday Bhan, and Subhrangsu S. Mandal, “Nuclear Receptors and NR-coregulators: Mechanism of Action and Cell Signaling,” Gene Regulation, Epigenetics and Hormone Signaling, pp. 289–328, 2017. View at Publisher · View at Google Scholar
  • Yujung Jung, Yongkai Cao, Suresh Paudel, Goo Yoon, Seung Hoon Cheon, Gyu-Un Bae, Li Tai Jin, Yong Kee Kim, and Su-Nam Kim, “Antidiabetic effect of SN158 through PPARα/γ dual activation in ob/ob mice,” Chemico-Biological Interactions, 2017. View at Publisher · View at Google Scholar
  • Juan M. Zolezzi, Manuel J. Santos, Sussy Bastías-Candia, Claudio Pinto, Juan A. Godoy, and Nibaldo C. Inestrosa, “PPARs in the central nervous system: roles in neurodegeneration and neuroinflammation,” Biological Reviews, 2017. View at Publisher · View at Google Scholar
  • Tingting Ren, Juanjuan Zhu, Lili Zhu, and Mingliang Cheng, “The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α,” Nutrients, vol. 9, no. 3, pp. 198, 2017. View at Publisher · View at Google Scholar
  • Sandhya Mamindla, Venkata S. R. G. P. Koganti, Nagaraju Ravouru, and Bharathi Koganti, “Effect of Cinnamomum cassia on the pharmacokinetics and pharmacodynamics of pioglitazone,” Current Clinical Pharmacology, vol. 12, no. 1, pp. 41–49, 2017. View at Publisher · View at Google Scholar
  • Wei Yi, Jingjing Shi, Guanguan Zhao, X. Edward Zhou, Kelly Suino-Powell, Karsten Melcher, and H. Eric Xu, “Identification of a novel selective PPARγ ligand with a unique binding mode and improved therapeutic profile in vitro,” Scientific Reports, vol. 7, pp. 41487, 2017. View at Publisher · View at Google Scholar
  • Lars Porskjær Christensen, and Rime Bahij El-Houri, “Development of an In Vitro Screening Platform for the Identification of Partial PPARγ Agonists as a Source for Antidiabetic Lead Compounds,” Molecules, vol. 23, no. 10, pp. 2431, 2018. View at Publisher · View at Google Scholar
  • Amin Majdalawieh, and Hyo-Sung Ro, “PPARγ1 and LXRα face a new regulator of macrophage cholesterol homeostasis and inflammatory responsiveness, AEBP1,” Nuclear Receptor Signaling, vol. 8, no. 1, pp. nrs.08004, 2018. View at Publisher · View at Google Scholar
  • Rong-Xing Liu, Yan Ma, Xue-Lian Hu, Yun-Peng Liao, Xiang-Nan Hu, Bai-Cheng He, and Wen-Juan Sun, “Pioglitazone/metformin adduct regulates insulin secretion and inhibits high glucose-induced apoptosis via p21-p53-MDM2 signaling in INS-1 cells,” Journal of Cellular Biochemistry, 2018. View at Publisher · View at Google Scholar
  • Tao Nie, Shiting Zhao, Liufeng Mao, Yiting Yang, Wei Sun, Xiaoliang Lin, Shuo Liu, Kuai Li, Yirong Sun, Peng Li, Zhiguang Zhou, Shaoqiang Lin, Xiaoyan Hui, Aimin Xu, Chung Wah Ma, Yong Xu, Cunchuan Wang, P Rod Dunbar, and Donghai Wu, “ The natural compound, formononetin, extracted from Astragalus membranaceus increases adipocyte thermogenesis by modulating PPARγ activity ,” British Journal of Pharmacology, 2018. View at Publisher · View at Google Scholar
  • Helder Veras Ribeiro Filho, Natália Bernardi Videira, Aline Villanova Bridi, Thais Helena Tittanegro, Fernanda Aparecida Helena Batista, José Geraldo de Carvalho Pereira, Paulo Sérgio Lopes de Oliveira, Marcio Chaim Bajgelman, Albane Le Maire, and Ana Carolina Migliorini Figueira, “Screening for PPAR Non-Agonist Ligands Followed by Characterization of a Hit, AM-879, with Additional No-Adipogenic and cdk5-Mediated Phosphorylation Inhibition Properties,” Frontiers in Endocrinology, vol. 9, 2018. View at Publisher · View at Google Scholar