Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Role of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in Different Disease States: Recent Updates

Author(s): Suvadeep Mal, Ashish Ranjan Dwivedi, Vijay Kumar, Naveen Kumar, Bhupinder Kumar and Vinod Kumar*

Volume 28, Issue 16, 2021

Published on: 16 July, 2020

Page: [3193 - 3215] Pages: 23

DOI: 10.2174/0929867327666200716113136

Price: $65

Abstract

Peroxisome proliferator-activated receptor (PPAR), a ligand dependant transcription factor, is a member of the nuclear receptor superfamily. PPAR exists in three isoforms i.e. PPAR alpha (PPARα), PPAR beta (PPARβ), and PPAR gamma (PPARγ). These are multi-functional transcription factors and help in regulating inflammation, type 2 diabetes, lipid concentration in the body, metastasis, and tumor growth or angiogenesis. Activation of PPARγ causes inhibition of growth of cultured human breast, gastric, lung, prostate, and other cancer cells. PPARγ is mainly involved in fatty acid storage, glucose metabolism, and homeostasis and adipogenesis regulation. A large number of natural and synthetic ligands bind to PPARγ and modulate its activity. Ligands such as thiazolidinedione, troglitazone, rosiglitazone, pioglitazone effectively bind to PPARγ; however, most of these were found to display severe side effects such as hepatotoxicity, weight gain, cardiovascular complications and bladder tumor. Now the focus is shifted towards the development of dual-acting or pan PPAR ligands. The current review article describes the functions and role of PPARγ in various disease states. In addition, recently reported PPARγ ligands and pan PPAR ligands were discussed in detail. It is envisaged that the present review article may help in the development of potent PPAR ligands with no or minimal side effects.

Keywords: proliferator-activated receptor, PPAR gamma, pan PPAR ligands, diabetes, cancer, bladder tumor.

« Previous Next »
[1]
Ramos, K.; Nanez, A. Introduction and overview of receptor systems.In:Comprehensive Toxicology, 2nd ed; Elsevier Inc., 2010, pp. 71-80.
[http://dx.doi.org/10.1016/B978-0-08-046884-6.00205-0]
[2]
Kersten, S.; Desvergne, B.; Wahli, W. Roles of PPARs in health and disease. Nature, 2000, 405(6785), 421-424.
[http://dx.doi.org/10.1038/35013000] [PMID: 10839530]
[3]
Spiegelman, B.M. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes, 1998, 47(4), 507-514.
[http://dx.doi.org/10.2337/diabetes.47.4.507] [PMID: 9568680]
[4]
Mukherjee, R.; Davies, P.J.; Crombie, D.L.; Bischoff, E.D.; Cesario, R.M.; Jow, L.; Hamann, L.G.; Boehm, M.F.; Mondon, C.E.; Nadzan, A.M.; Paterniti, J.R. Jr.; Heyman, R.A. Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists. Nature, 1997, 386(6623), 407-410.
[http://dx.doi.org/10.1038/386407a0] [PMID: 9121558]
[5]
Ricote, M.; Glass, C.K. PPARs and molecular mechanisms of transrepression. Biochim. Biophys. Acta, 2007, 1771(8), 926-935.
[http://dx.doi.org/10.1016/j.bbalip.2007.02.013] [PMID: 17433773]
[6]
Viswakarma, N.; Jia, Y.; Bai, L.; Vluggens, A.; Borensztajn, J.; Xu, J.; Reddy, J.K. Coactivators in PPAR-regulated gene expression. PPAR Res., 2010, 2010,250126.
[http://dx.doi.org/10.1155/2010/250126] [PMID: 20814439]
[7]
Martin, H. Role of PPAR-gamma in inflammation. Prospects for therapeutic intervention by food components. Mutat. Res., 2010, 690(1-2), 57-63.
[http://dx.doi.org/10.1016/j.mrfmmm.2009.09.009] [PMID: 20973164]
[8]
AlSaleh, A.; Sanders, T.A.; O’Dell, S.D. Effect of interaction between PPARG, PPARA and ADIPOQ gene variants and dietary fatty acids on plasma lipid profile and adiponectin concentration in a large intervention study. Proc. Nutr. Soc., 2012, 71(1), 141-153.
[http://dx.doi.org/10.1017/S0029665111003181] [PMID: 22040870]
[9]
Olefsky, J.M. Treatment of insulin resistance with peroxisome proliferator-activated receptor γ agonists. J. Clin. Invest., 2000, 106(4), 467-472.
[http://dx.doi.org/10.1172/JCI10843] [PMID: 10953021]
[10]
Yu, X.; Shao, X.G.; Sun, H.; Li, Y.N.; Yang, J.; Deng, Y.C.; Huang, Y.G. Activation of cerebral peroxisome proliferator-activated receptors gamma exerts neuroprotection by inhibiting oxidative stress following pilocarpine-induced status epilepticus. Brain Res., 2008, 1200, 146-158.
[http://dx.doi.org/10.1016/j.brainres.2008.01.047] [PMID: 18289512]
[11]
Frankenberg, A.D.V.; Reis, A.F.; Gerchman, F. Relationships between adiponectin levels, the metabolic syndrome, and type 2 diabetes: a literature review. Arch. Endocrinol. Metab., 2017, 61(6), 614-622.
[http://dx.doi.org/10.1590/2359-3997000000316] [PMID: 29412387]
[12]
Grygiel-Górniak, B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications-a review. Nutr. J., 2014, 13, 17.
[http://dx.doi.org/10.1186/1475-2891-13-17] [PMID: 24524207]
[13]
Kliewer, S.A.; Xu, H.E.; Lambert, M.H.; Willson, T.M. Peroxisome proliferator-activated receptors: from genes to physiology. Recent Prog. Horm. Res., 2001, 56, 239-263.
[http://dx.doi.org/10.1210/rp.56.1.239] [PMID: 11237216]
[14]
Rakhshandehroo, M.; Knoch, B.; Müller, M.; Kersten, S. Peroxisome proliferator-activated receptor alpha target genes. PPAR Res., 2010, 2010,612089.
[http://dx.doi.org/10.1155/2010/612089] [PMID: 20936127]
[15]
Krey, G.; Keller, H.; Mahfoudi, A.; Medin, J.; Ozato, K.; Dreyer, C.; Wahli, W. Xenopus peroxisome proliferator activated receptors: genomic organization, response element recognition, heterodimer formation with retinoid X receptor and activation by fatty acids. J. Steroid Biochem. Mol. Biol., 1993, 47(1-6), 65-73.
[http://dx.doi.org/10.1016/0960-0760(93)90058-5] [PMID: 8274443]
[16]
Schmidt, A.; Endo, N.; Rutledge, S.J.; Vogel, R.; Shinar, D.; Rodan, G.A. Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol. Endocrinol., 1992, 6(10), 1634-1641.
[http://dx.doi.org/10.1210/mend.6.10.1333051] [PMID: 1333051]
[17]
Reilly, S.M.; Lee, C.H. PPAR δ as a therapeutic target in metabolic disease. FEBS Lett., 2008, 582(1), 26-31.
[http://dx.doi.org/10.1016/j.febslet.2007.11.040] [PMID: 18036566]
[18]
Hall, M.G.; Quignodon, L.; Desvergne, B. Peroxisome proliferator-activated receptor. PPAR Res., 2008, 2008,780452.
[http://dx.doi.org/10.1155/2008/780452] [PMID: 19009042]
[19]
Guan, Y.; Zhang, Y.; Schneider, A.; Davis, L.; Breyer, R.M.; Breyer, M.D. Peroxisome proliferator-activated receptor-γ activity is associated with renal microvasculature. Am. J. Physiol. Renal Physiol., 2001, 281(6), F1036-F1046.
[http://dx.doi.org/10.1152/ajprenal.0025.2001] [PMID: 11704554]
[20]
Seufert, S.; Coras, R.; Tränkle, C.; Zlotos, D.P.; Blümcke, I.; Tatenhorst, L.; Heneka, M.T.; Hahnen, E. PPAR gamma activators: off-target against glioma cell migration and brain invasion. PPAR Res., 2008, 2008,513943.
[http://dx.doi.org/10.1155/2008/513943] [PMID: 18815619]
[21]
Blanquicett, C.; Roman, J.; Hart, C.M. Thiazolidinediones as anti-cancer agents. Cancer Ther, 2008, 6(A), 25-34.
[PMID: 19079765]
[22]
Desvergne, B.; Wahli, W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr. Rev., 1999, 20(5), 649-688.
[http://dx.doi.org/10.1210/edrv.20.5.0380] [PMID: 10529898]
[23]
Chandra, V.; Huang, P.; Hamuro, Y.; Raghuram, S.; Wang, Y.; Burris, T.P.; Rastinejad, F. Structure of the intact PPAR-γ-RXR- nuclear receptor complex on DNA. Nature, 2008, 456(7220), 350-356.
[http://dx.doi.org/10.1038/nature07413] [PMID: 19043829]
[24]
Suzuki, S.; Sasaki, S.; Morita, H.; Oki, Y.; Turiya, D.; Ito, T.; Misawa, H.; Ishizuka, K.; Nakamura, H. The role of the amino-terminal domain in the interaction of unliganded peroxisome proliferator-activated receptor gamma-2 with nuclear receptor co-repressor. J. Mol. Endocrinol., 2010, 45(3), 133-145.
[http://dx.doi.org/10.1677/JME-10-0007] [PMID: 20587609]
[25]
Nolte, R.T.; Wisely, G.B.; Westin, S.; Cobb, J.E.; Lambert, M.H.; Kurokawa, R.; Rosenfeld, M.G.; Willson, T.M.; Glass, C.K.; Milburn, M.V. Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-γ. Nature, 1998, 395(6698), 137-143.
[http://dx.doi.org/10.1038/25931] [PMID: 9744270]
[26]
Ji, C.G.; Zhang, J.Z. Protein polarization is critical to stabilizing AF-2 and helix-2′ domains in ligand binding to PPAR-γ. J. Am. Chem. Soc., 2008, 130(50), 17129-17133.
[http://dx.doi.org/10.1021/ja807374x] [PMID: 19007119]
[27]
Zieleniak, A.; Wójcik, M.; Woźniak, L.A. Structure and physiological functions of the human peroxisome proliferator-activated receptor γ. Arch. Immunol. Ther. Exp. (Warsz.), 2008, 56(5), 331-345.
[http://dx.doi.org/10.1007/s00005-008-0037-y] [PMID: 18836859]
[28]
Gampe, R.T., Jr; Montana, V.G.; Lambert, M.H.; Miller, A.B.; Bledsoe, R.K.; Milburn, M.V.; Kliewer, S.A.; Willson, T.M.; Xu, H.E. Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors. Mol. Cell, 2000, 5(3), 545-555.
[http://dx.doi.org/10.1016/S1097-2765(00)80448-7] [PMID: 10882139]
[29]
Pochetti, G.; Godio, C.; Mitro, N.; Caruso, D.; Galmozzi, A.; Scurati, S.; Loiodice, F.; Fracchiolla, G.; Tortorella, P.; Laghezza, A.; Lavecchia, A.; Novellino, E.; Mazza, F.; Crestani, M. Insights into the mechanism of partial agonism: crystal structures of the peroxisome proliferator-activated receptor γ ligand-binding domain in the complex with two enantiomeric ligands. J. Biol. Chem., 2007, 282(23), 17314-17324.
[http://dx.doi.org/10.1074/jbc.M702316200] [PMID: 17403688]
[30]
Xu, H.E.; Stanley, T.B.; Montana, V.G.; Lambert, M.H.; Shearer, B.G.; Cobb, J.E.; McKee, D.D.; Galardi, C.M.; Plunket, K.D.; Nolte, R.T.; Parks, D.J.; Moore, J.T.; Kliewer, S.A.; Willson, T.M.; Stimmel, J.B. Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARalpha. Nature, 2002, 415(6873), 813-817.
[http://dx.doi.org/10.1038/415813a] [PMID: 11845213]
[31]
Liu, D.; Zeng, B.X.; Zhang, S.H.; Yao, S.L. Rosiglitazone, an agonist of peroxisome proliferator-activated receptor γ, reduces pulmonary inflammatory response in a rat model of endotoxemia. Inflamm. Res., 2005, 54(11), 464-470.
[http://dx.doi.org/10.1007/s00011-005-1379-0] [PMID: 16307220]
[32]
Sharma, A.K.; Bharti, S.; Ojha, S.; Bhatia, J.; Kumar, N.; Ray, R.; Kumari, S.; Arya, D.S. Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes. Br. J. Nutr., 2011, 106(11), 1713-1723.
[http://dx.doi.org/10.1017/S000711451100225X] [PMID: 21736771]
[33]
Kim, E.H.; Tolhurst, A.T.; Szeto, H.H.; Cho, S.H. Targeting CD36-mediated inflammation reduces acute brain injury in transient, but not permanent, ischemic stroke. CNS Neurosci. Ther., 2015, 21(4), 385-391.
[http://dx.doi.org/10.1111/cns.12326] [PMID: 25216018]
[34]
Ikmal, S.I.Q.S.; Huri, H.Z.; Vethakkan, S.R.; Ahmad, W.A.W. Potential biomarkers of insulin resistance and atherosclerosis in type 2 diabetes mellitus patients with coronary artery disease. Int. J. Endocrinol., 2013, 2013,698567.
[http://dx.doi.org/10.1155/2013/698567] [PMID: 24282409]
[35]
Kim, S.H.; Hong, J.H.; Lee, Y.C. Ursolic acid, a potential PPARγ agonist, suppresses ovalbumin-induced airway inflammation and penh by down-regulating IL-5, IL-13, and IL-17 in a mouse model of allergic asthma. Eur. J. Pharmacol., 2013, 701(1-3), 131-143.
[http://dx.doi.org/10.1016/j.ejphar.2012.11.033] [PMID: 23201068]
[36]
Zhan, C.D.; Sindhu, R.K.; Pang, J.; Ehdaie, A.; Vaziri, N.D. Superoxide dismutase, catalase and glutathione peroxidase in the spontaneously hypertensive rat kidney: effect of antioxidant-rich diet. J. Hypertens., 2004, 22(10), 2025-2033.
[http://dx.doi.org/10.1097/00004872-200410000-00027] [PMID: 15361776]
[37]
Kallenberger, B.C.; Love, J.D.; Chatterjee, V.K.K.; Schwabe, J.W. A dynamic mechanism of nuclear receptor activation and its perturbation in a human disease. Nat. Struct. Biol., 2003, 10(2), 136-140.
[http://dx.doi.org/10.1038/nsb892] [PMID: 12536206]
[38]
Yuan, G.; Chen, X.; Li, D. Modulation of peroxisome proliferator-activated receptor gamma (PPAR γ) by conjugated fatty acid in obesity and inflammatory bowel disease. J. Agric. Food Chem., 2015, 63(7), 1883-1895.
[http://dx.doi.org/10.1021/jf505050c] [PMID: 25634802]
[39]
Villapol, S. Roles of peroxisome proliferator-activated receptor gamma on brain and peripheral inflammation. Cell. Mol. Neurobiol., 2018, 38(1), 121-132.
[http://dx.doi.org/10.1007/s10571-017-0554-5] [PMID: 28975471]
[40]
Ballesteros, I.; Cuartero, M.I.; Pradillo, J.M.; de la Parra, J.; Pérez-Ruiz, A.; Corbí, A.; Ricote, M.; Hamilton, J.A.; Sobrado, M.; Vivancos, J.; Nombela, F.; Lizasoain, I.; Moro, M.A. Rosiglitazone-induced CD36 up-regulation resolves inflammation by PPARγ and 5-LO-dependent pathways. J. Leukoc. Biol., 2014, 95(4), 587-598.
[http://dx.doi.org/10.1189/jlb.0613326] [PMID: 24338629]
[41]
Heneka, M.T.; Klockgether, T.; Feinstein, D.L. Peroxisome proliferator-activated receptor-γ ligands reduce neuronal inducible nitric oxide synthase expression and cell death in vivo. J. Neurosci., 2000, 20(18), 6862-6867.
[http://dx.doi.org/10.1523/JNEUROSCI.20-18-06862.2000] [PMID: 10995830]
[42]
Kapadia, R.; Yi, J.H.; Vemuganti, R. Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists. Front. Biosci., 2008, 13, 1813-1826.
[http://dx.doi.org/10.2741/2802] [PMID: 17981670]
[43]
Lenglet, S.; Montecucco, F.; Mach, F. Role of matrix metalloproteinases in animal models of ischemic stroke. Curr. Vasc. Pharmacol., 2015, 13(2), 161-166.
[http://dx.doi.org/10.2174/15701611113116660161] [PMID: 24188490]
[44]
Akiyama, T.E.; Meinke, P.T.; Berger, J.P. PPAR ligands: potential therapies for metabolic syndrome. Curr. Diab. Rep., 2005, 5(1), 45-52.
[http://dx.doi.org/10.1007/s11892-005-0067-3] [PMID: 15663917]
[45]
Chinetti, G.; Fruchart, J.C.; Staels, B. Peroxisome proliferator-activated receptors (PPARs): nuclear receptors with functions in the vascular wall. Z. Kardiol., 2001, 90(Suppl. 3), 125-132.
[http://dx.doi.org/10.1007/s003920170034] [PMID: 11374025]
[46]
Blaschke, F.; Takata, Y.; Caglayan, E.; Law, R.E.; Hsueh, W.A. Obesity, peroxisome proliferator-activated receptor, and atherosclerosis in type 2 diabetes. Arterioscler. Thromb. Vasc. Biol., 2006, 26(1), 28-40.
[http://dx.doi.org/10.1161/01.ATV.0000191663.12164.77] [PMID: 16239592]
[47]
Yao, Y.; Xu, X.H.; Jin, L. Macrophage polarization in physiological and pathological pregnancy. Front. Immunol., 2019, 10, 792.
[http://dx.doi.org/10.3389/fimmu.2019.00792] [PMID: 31037072]
[48]
Luo, W.; Xu, Q.; Wang, Q.; Wu, H.; Hua, J. Effect of modulation of PPAR-γ activity on Kupffer cells M1/M2 polarization in the development of non-alcoholic fatty liver disease. Sci. Rep., 2017, 7, 44612.
[http://dx.doi.org/10.1038/srep44612] [PMID: 28300213]
[49]
Cicchese, J.M.; Evans, S.; Hult, C.; Joslyn, L.R.; Wessler, T.; Millar, J.A.; Marino, S.; Cilfone, N.A.; Mattila, J.T.; Linderman, J.J.; Kirschner, D.E. Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology. Immunol. Rev., 2018, 285(1), 147-167.
[http://dx.doi.org/10.1111/imr.12671] [PMID: 30129209]
[50]
Phaniendra, A.; Jestadi, D.B.; Periyasamy, L. Free radicals: properties, sources, targets, and their implication in various diseases. Indian J. Clin. Biochem., 2015, 30(1), 11-26.
[http://dx.doi.org/10.1007/s12291-014-0446-0] [PMID: 25646037]
[51]
Kurutas, E.B. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr. J., 2016, 15(1), 71.
[http://dx.doi.org/10.1186/s12937-016-0186-5] [PMID: 27456681]
[52]
Lozano, D.; Gonzales-Portillo, G.S.; Acosta, S.; de la Pena, I.; Tajiri, N.; Kaneko, Y.; Borlongan, C.V. Neuroinflammatory responses to traumatic brain injury: etiology, clinical consequences, and therapeutic opportunities. Neuropsychiatr. Dis. Treat., 2015, 11, 97-106.
[http://dx.doi.org/10.2147/ndt.s65815] [PMID: 25657582]
[53]
Dunning, S.; Ur Rehman, A.; Tiebosch, M.H.; Hannivoort, R.A.; Haijer, F.W.; Woudenberg, J.; van den Heuvel, F.A.; Buist-Homan, M.; Faber, K.N.; Moshage, H. Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death. Biochim. Biophys. Acta, 2013, 1832(12), 2027-2034.
[http://dx.doi.org/10.1016/j.bbadis.2013.07.008] [PMID: 23871839]
[54]
Zarzuelo, M.J.; López-Sepúlveda, R.; Sánchez, M.; Romero, M.; Gómez-Guzmán, M.; Ungvary, Z.; Pérez-Vizcaíno, F.; Jiménez, R.; Duarte, J. SIRT1 inhibits NADPH oxidase activation and protects endothelial function in the rat aorta: implications for vascular aging. Biochem. Pharmacol., 2013, 85(9), 1288-1296.
[http://dx.doi.org/10.1016/j.bcp.2013.02.015] [PMID: 23422569]
[55]
Heneka, M.T.; Landreth, G.E. PPARs in the brain. Biochim. Biophys. Acta, 2007, 1771(8), 1031-1045.
[http://dx.doi.org/10.1016/j.bbalip.2007.04.016]] [PMID: 17569578]
[56]
Park, E.Y.; Cho, I.J.; Kim, S.G. Transactivation of the PPAR-responsive enhancer module in chemopreventive glutathione S-transferase gene by the peroxisome proliferator-activated receptor-γ and retinoid X receptor heterodimer. Cancer Res., 2004, 64(10), 3701-3713.
[http://dx.doi.org/10.1158/0008-5472.CAN-03-3924] [PMID: 15150131]
[57]
Nishida, N.; Yano, H.; Nishida, T.; Kamura, T.; Kojiro, M. Angiogenesis in cancer. Vasc. Health Risk Manag., 2006, 2(3), 213-219.
[http://dx.doi.org/10.2147/vhrm.2006.2.3.213] [PMID: 17326328]
[58]
Arany, Z.; Foo, S.Y.; Ma, Y.; Ruas, J.L.; Bommi-Reddy, A.; Girnun, G.; Cooper, M.; Laznik, D.; Chinsomboon, J.; Rangwala, S.M.; Baek, K.H.; Rosenzweig, A.; Spiegelman, B.M. HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1α. Nature, 2008, 451(7181), 1008-1012.
[http://dx.doi.org/10.1038/nature06613] [PMID: 18288196]
[59]
Reaven, G.M. Pathophysiology of insulin resistance in human disease. Physiol. Rev., 1995, 75(3), 473-486.
[http://dx.doi.org/10.1152/physrev.1995.75.3.473] [PMID: 7624391]
[60]
Wilcox, G. Insulin and insulin resistance. Clin. Biochem. Rev., 2005, 26(2), 19-39.
[PMID: 16278749]
[61]
Haber, L.M.; Hawkins, E.P.; Seilheimer, D.K.; Saleem, A. Fat overload syndrome. An autopsy study with evaluation of the coagulopathy. Am. J. Clin. Pathol., 1988, 90(2), 223-227.
[http://dx.doi.org/10.1093/ajcp/90.2.223] [PMID: 3394663]
[62]
Czech, M.P. Insulin action and resistance in obesity and type 2 diabetes. Nat. Med., 2017, 23(7), 804-814.
[http://dx.doi.org/10.1038/nm.4350] [PMID: 28697184]
[63]
Govers, R. Cellular regulation of glucose uptake by glucose transporter GLUT4. Adv. Clin. Chem., 2014, 66, 173-240.
[http://dx.doi.org/10.1016/B978-0-12-801401-1.00006-2] [PMID: 25344989]
[64]
Satoh, T. Molecular mechanisms for the regulation of insulin-stimulated glucose uptake by small guanosine triphosphatases in skeletal muscle and adipocytes. Int. J. Mol. Sci., 2014, 15(10), 18677-18692.
[http://dx.doi.org/10.3390/ijms151018677] [PMID: 25325535]
[65]
Russell, R.R., III; Bergeron, R.; Shulman, G.I.; Young, L.H. Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR. Am. J. Physiol., 1999, 277(2), H643-H649.
[http://dx.doi.org/10.1152/ajpheart.1999.277.2.h643] [PMID: 10444490]
[66]
Itoh, M.; Suganami, T.; Hachiya, R.; Ogawa, Y. Adipose tissue remodeling as homeostatic inflammation. Int. J. Inflamm., 2011, 2011,720926.
[http://dx.doi.org/10.4061/2011/720926] [PMID: 21755030]
[67]
Farmer, S.R. Regulation of PPARgamma activity during adipogenesis. Int. J. Obes., 2005, 29(Suppl. 1), S13-S16.
[http://dx.doi.org/10.1038/sj.ijo.0802907] [PMID: 15711576]
[68]
de Souza, C.J.; Eckhardt, M.; Gagen, K.; Dong, M.; Chen, W.; Laurent, D.; Burkey, B.F. Effects of pioglitazone on adipose tissue remodeling within the setting of obesity and insulin resistance. Diabetes, 2001, 50(8), 1863-1871.
[http://dx.doi.org/10.2337/diabetes.50.8.1863] [PMID: 11473050]
[69]
Glorian, M.; Duplus, E.; Beale, E.G.; Scott, D.K.; Granner, D.K.; Forest, C. A single element in the phosphoenolpyruvate carboxykinase gene mediates thiazolidinedione action specifically in adipocytes. Biochimie, 2001, 83(10), 933-943.
[http://dx.doi.org/10.1016/S0300-9084(01)01343-8] [PMID: 11728630]
[70]
Lin, J.; Handschin, C.; Spiegelman, B.M. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab., 2005, 1(6), 361-370.
[http://dx.doi.org/10.1016/j.cmet.2005.05.004] [PMID: 16054085]
[71]
Jamaluddin, M.S.; Weakley, S.M.; Yao, Q.; Chen, C. Resistin: functional roles and therapeutic considerations for cardiovascular disease. Br. J. Pharmacol., 2012, 165(3), 622-632.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01369.x] [PMID: 21545576]
[72]
Nieva-Vazquez, A.; Pérez-Fuentes, R.; Torres-Rasgado, E.; López-López, J.G.; Romero, J.R. Serum resistin levels are associated with adiposity and insulin sensitivity in obese Hispanic subjects. Metab. Syndr. Relat. Disord., 2014, 12(2), 143-148.
[http://dx.doi.org/10.1089/met.2013.0118] [PMID: 24266722]
[73]
Patel, L.; Buckels, A.C.; Kinghorn, I.J.; Murdock, P.R.; Holbrook, J.D.; Plumpton, C.; Macphee, C.H.; Smith, S.A. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem. Biophys. Res. Commun., 2003, 300(2), 472-476.
[http://dx.doi.org/10.1016/S0006-291X(02)02841-3] [PMID: 12504108]
[74]
Kadowaki, T.; Yamauchi, T.; Kubota, N.; Hara, K.; Ueki, K.; Tobe, K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J. Clin. Invest., 2006, 116(7), 1784-1792.
[http://dx.doi.org/10.1172/JCI29126] [PMID: 16823476]
[75]
Maeda, N.; Takahashi, M.; Funahashi, T.; Kihara, S.; Nishizawa, H.; Kishida, K.; Nagaretani, H.; Matsuda, M.; Komuro, R.; Ouchi, N.; Kuriyama, H.; Hotta, K.; Nakamura, T.; Shimomura, I.; Matsuzawa, Y. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes, 2001, 50(9), 2094-2099.
[http://dx.doi.org/10.2337/diabetes.50.9.2094] [PMID: 11522676]
[76]
Achari, A.E.; Jain, S.K. Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction. Int. J. Mol. Sci., 2017, 18(6), 1321.
[http://dx.doi.org/10.3390/ijms18061321] [PMID: 28635626]
[77]
Hirayama, D.; Iida, T.; Nakase, H. The phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis. Int. J. Mol. Sci., 2017, 19(1), 92.
[http://dx.doi.org/10.3390/ijms19010092] [PMID: 29286292]
[78]
Cancello, R.; Henegar, C.; Viguerie, N.; Taleb, S.; Poitou, C.; Rouault, C.; Coupaye, M.; Pelloux, V.; Hugol, D.; Bouillot, J.L.; Bouloumié, A.; Barbatelli, G.; Cinti, S.; Svensson, P.A.; Barsh, G.S.; Zucker, J.D.; Basdevant, A.; Langin, D.; Clément, K. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes, 2005, 54(8), 2277-2286.
[http://dx.doi.org/10.2337/diabetes.54.8.2277] [PMID: 16046292]
[79]
Apovian, C.M.; Bigornia, S.; Mott, M.; Meyers, M.R.; Ulloor, J.; Gagua, M.; McDonnell, M.; Hess, D.; Joseph, L.; Gokce, N. Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects. Arterioscler. Thromb. Vasc. Biol., 2008, 28(9), 1654-1659.
[http://dx.doi.org/10.1161/ATVBAHA.108.170316] [PMID: 18566296]
[80]
Kersten, S. Peroxisome proliferator activated receptors and lipoprotein metabolism. PPAR Res., 2008, 2008,132960.
[http://dx.doi.org/10.1155/2008/132960] [PMID: 18288277]
[81]
Elrod, H.A.; Sun, S.Y. PPARγ and apoptosis in cancer. PPAR Res., 2008, 2008,704165.
[http://dx.doi.org/10.1155/2008/704165] [PMID: 18615184]
[82]
Tontonoz, P.; Singer, S.; Forman, B.M.; Sarraf, P.; Fletcher, J.A.; Fletcher, C.D.; Brun, R.P.; Mueller, E.; Altiok, S.; Oppenheim, H.; Evans, R.M.; Spiegelman, B.M. Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor γ and the retinoid X receptor. Proc. Natl. Acad. Sci. USA, 1997, 94(1), 237-241.
[http://dx.doi.org/10.1073/pnas.94.1.237] [PMID: 8990192]
[83]
Yang, Z.; Bagheri-Yarmand, R.; Balasenthil, S.; Hortobagyi, G.; Sahin, A.A.; Barnes, C.J.; Kumar, R. HER2 regulation of peroxisome proliferator-activated receptor γ (PPARgamma) expression and sensitivity of breast cancer cells to PPARgamma ligand therapy. Clin. Cancer Res., 2003, 9(8), 3198-3203.
[PMID: 12912973]
[84]
Betz, M.J.; Shapiro, I.; Fassnacht, M.; Hahner, S.; Reincke, M.; Beuschlein, F. German and Austrian Adrenal Network. Peroxisome proliferator-activated receptor-γ agonists suppress adrenocortical tumor cell proliferation and induce differentiation. J. Clin. Endocrinol. Metab., 2005, 90(7), 3886-3896.
[http://dx.doi.org/10.1210/jc.2004-1267] [PMID: 15886257]
[85]
Shiau, C.W.; Yang, C.C.; Kulp, S.K.; Chen, K.F.; Chen, C.S.; Huang, J.W.; Chen, C.S. Thiazolidenediones mediate apoptosis in prostate cancer cells in part through inhibition of Bcl-xL/Bcl-2 functions independently of PPARgamma. Cancer Res., 2005, 65(4), 1561-1569.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-1677] [PMID: 15735046]
[86]
Tachibana, K.; Yamasaki, D.; Ishimoto, K.; Doi, T. The role of PPARs in cancer. PPAR Res., 2008, 2008,102737.
[http://dx.doi.org/10.1155/2008/102737] [PMID: 18584037]
[87]
Toyoda, M.; Takagi, H.; Horiguchi, N.; Kakizaki, S.; Sato, K.; Takayama, H.; Mori, M. A ligand for peroxisome proliferator activated receptor γ inhibits cell growth and induces apoptosis in human liver cancer cells. Gut, 2002, 50(4), 563-567.
[http://dx.doi.org/10.1136/gut.50.4.563] [PMID: 11889080]
[88]
Spencer, C.M.; Markham, A. Troglitazone. Drugs, 1997, 54(1), 89-101.
[http://dx.doi.org/10.2165/00003495-199754010-00010] [PMID: 9211083]
[89]
Buchanan, T.A.; Xiang, A.H.; Peters, R.K.; Kjos, S.L.; Marroquin, A.; Goico, J.; Ochoa, C.; Tan, S.; Berkowitz, K.; Hodis, H.N.; Azen, S.P. Preservation of pancreatic β-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk hispanic women. Diabetes, 2002, 51(9), 2796-2803.
[http://dx.doi.org/10.2337/diabetes.51.9.2796] [PMID: 12196473]
[90]
Faich, G.A.; Moseley, R.H. Troglitazone (rezulin) and hepatic injury. Pharmacoepidemiol. Drug Saf., 2001, 10(6), 537-547.
[http://dx.doi.org/10.1002/pds.652] [PMID: 11828837]
[91]
Bosch, J.; Yusuf, S.; Gerstein, H.C.; Pogue, J.; Sheridan, P.; Dagenais, G.; Diaz, R.; Avezum, A.; Lanas, F.; Probstfield, J.; Fodor, G.; Holman, R.R. DREAM Trial Investigators Effect of ramipril on the incidence of diabetes. N. Engl. J. Med., 2006, 355(15), 1551-1562.
[http://dx.doi.org/10.1056/NEJMoa065061] [PMID: 16980380]
[92]
Wagstaff, A.J.; Goa, K.L. Rosiglitazone: a review of its use in the management of type 2 diabetes mellitus. Drugs, 2002, 62(12), 1805-1837.
[http://dx.doi.org/10.2165/00003495-200262120-00007] [PMID: 12149047]
[93]
Gross, B.; Staels, B. PPAR agonists: multimodal drugs for the treatment of type-2 diabetes. Best Pract. Res. Clin. Endocrinol. Metab., 2007, 21(4), 687-710.
[http://dx.doi.org/10.1016/j.beem.2007.09.004] [PMID: 18054742]
[94]
Waugh, J.; Keating, G.M.; Plosker, G.L.; Easthope, S.; Robinson, D.M. Pioglitazone: a review of its use in type 2 diabetes mellitus. Drugs, 2006, 66(1), 85-109.
[http://dx.doi.org/10.2165/00003495-200666010-00005] [PMID: 16398569]
[95]
Lewis, J.D.; Ferrara, A.; Peng, T.; Hedderson, M.; Bilker, W.B.; Quesenberry, C.P., Jr; Vaughn, D.J.; Nessel, L.; Selby, J.; Strom, B.L. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care, 2011, 34(4), 916-922.
[http://dx.doi.org/10.2337/dc10-1068] [PMID: 21447663]
[96]
Lee, Y.H.; Kim, J.H.; Kim, S.R.; Jin, H.Y.; Rhee, E.J.; Cho, Y.M.; Lee, B.W. Lobeglitazone, a novel thiazolidinedione, improves non-alcoholic fatty liver disease in type 2 diabetes: its efficacy and predictive factors related to responsiveness. J. Korean Med. Sci., 2017, 32(1), 60-69.
[http://dx.doi.org/10.3346/jkms.2017.32.1.60] [PMID: 27914133]
[97]
Kaul, U.; Parmar, D.; Manjunath, K.; Shah, M.; Parmar, K.; Patil, K.P.; Jaiswal, A. New dual peroxisome proliferator activated receptor agonist-saroglitazar in diabetic dyslipidemia and non-alcoholic fatty liver disease: integrated analysis of the real world evidence. Cardiovasc. Diabetol., 2019, 18(1), 80.
[http://dx.doi.org/10.1186/s12933-019-0884-3] [PMID: 31208414]
[98]
Joshi, S.R. Saroglitazar for the treatment of dyslipidemia in diabetic patients. Expert Opin. Pharmacother., 2015, 16(4), 597-606.
[http://dx.doi.org/10.1517/14656566.2015.1009894] [PMID: 25674933]
[99]
Chen, Y.; Chen, H.; Birnbaum, Y.; Nanhwan, M.K.; Bajaj, M.; Ye, Y.; Qian, J. Aleglitazar, a dual peroxisome proliferator-activated receptor-α and -γ agonist, protects cardiomyocytes against the adverse effects of hyperglycaemia. Diab. Vasc. Dis. Res., 2017, 14(2), 152-162.
[http://dx.doi.org/10.1177/1479164116679081] [PMID: 28111985]
[100]
Shibata, T.; Takeuchi, S.; Yokota, S.; Kakimoto, K.; Yonemori, F.; Wakitani, K. Effects of peroxisome proliferator-activated receptor-α and -γ agonist, JTT-501, on diabetic complications in Zucker diabetic fatty rats. Br. J. Pharmacol., 2000, 130(3), 495-504.
[http://dx.doi.org/10.1038/sj.bjp.0703328] [PMID: 10821776]
[101]
Tenenbaum, A.; Motro, M.; Fisman, E.Z. Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons. Cardiovasc. Diabetol., 2005, 4(1), 14.
[http://dx.doi.org/10.1186/1475-2840-4-14] [PMID: 16168052]
[102]
Rudolph, J.; Chen, L.; Majumdar, D.; Bullock, W.H.; Burns, M.; Claus, T.; Dela Cruz, F.E.; Daly, M.; Ehrgott, F.J.; Johnson, J.S.; Livingston, J.N.; Schoenleber, R.W.; Shapiro, J.; Yang, L.; Tsutsumi, M.; Ma, X. Indanylacetic acid derivatives carrying 4-thiazolyl-phenoxy tail groups, a new class of potent PPAR α/γ/δ pan agonists: synthesis, structure-activity relationship, and in vivo efficacy. J. Med. Chem., 2007, 50(5), 984-1000.
[http://dx.doi.org/10.1021/jm061299k] [PMID: 17274610]
[103]
Wright, H.M.; Clish, C.B.; Mikami, T.; Hauser, S.; Yanagi, K.; Hiramatsu, R.; Serhan, C.N.; Spiegelman, B.M. A synthetic antagonist for the peroxisome proliferator-activated receptor γ inhibits adipocyte differentiation. J. Biol. Chem., 2000, 275(3), 1873-1877.
[http://dx.doi.org/10.1074/jbc.275.3.1873] [PMID: 10636887]
[104]
Seargent, J.M.; Yates, E.A.; Gill, J.H. GW9662, a potent antagonist of PPARgamma, inhibits growth of breast tumour cells and promotes the anticancer effects of the PPARgamma agonist rosiglitazone, independently of PPARgamma activation. Br. J. Pharmacol., 2004, 143(8), 933-937.
[http://dx.doi.org/10.1038/sj.bjp.0705973] [PMID: 15533890]
[105]
Park, H.S.; Kim, S.H.; Kim, Y.S.; Ryu, S.Y.; Hwang, J.T.; Yang, H.J.; Kim, G.H.; Kwon, D.Y.; Kim, M.S. Luteolin inhibits adipogenic differentiation by regulating PPARgamma activation. Biofactors, 2009, 35(4), 373-379.
[http://dx.doi.org/10.1002/biof.38] [PMID: 19353690]
[106]
Lee, G.; Elwood, F.; McNally, J.; Weiszmann, J.; Lindstrom, M.; Amaral, K.; Nakamura, M.; Miao, S.; Cao, P.; Learned, R.M.; Chen, J.L.; Li, Y. T0070907, a selective ligand for peroxisome proliferator-activated receptor γ, functions as an antagonist of biochemical and cellular activities. J. Biol. Chem., 2002, 277(22), 19649-19657.
[http://dx.doi.org/10.1074/jbc.M200743200] [PMID: 11877444]
[107]
Rieusset, J.; Touri, F.; Michalik, L.; Escher, P.; Desvergne, B.; Niesor, E.; Wahli, W. A new selective peroxisome proliferator-activated receptor γ antagonist with antiobesity and antidiabetic activity. Mol. Endocrinol., 2002, 16(11), 2628-2644.
[http://dx.doi.org/10.1210/me.2002-0036] [PMID: 12403851]
[108]
Huang, C.; Zhang, Y.; Gong, Z.; Sheng, X.; Li, Z.; Zhang, W.; Qin, Y. Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARgamma pathway. Biochem. Biophys. Res. Commun., 2006, 348(2), 571-578.
[http://dx.doi.org/10.1016/j.bbrc.2006.07.095] [PMID: 16890192]
[109]
Niu, H.; Wang, W.; Li, J.; Lei, Y.; Zhao, Y.; Yang, W.; Zhao, C.; Lin, B.; Song, S.; Wang, S. A novel structural class of coumarin-chalcone fibrates as PPARα/γ agonists with potent antioxidant activities: Design, synthesis, biological evaluation and molecular docking studies. Eur. J. Med. Chem., 2017, 138, 212-220.
[http://dx.doi.org/10.1016/j.ejmech.2017.06.033] [PMID: 28667876]
[110]
Darwish, K.M.; Salama, I.; Mostafa, S.; Gomaa, M.S.; Helal, M.A. Design, synthesis, and biological evaluation of novel thiazolidinediones as PPARγ/FFAR1 dual agonists. Eur. J. Med. Chem., 2016, 109, 157-172.
[http://dx.doi.org/10.1016/j.ejmech.2015.12.049] [PMID: 26774923]
[111]
Hara, T.; Hirasawa, A.; Ichimura, A.; Kimura, I.; Tsujimoto, G. Free fatty acid receptors FFAR1 and GPR120 as novel therapeutic targets for metabolic disorders. J. Pharm. Sci., 2011, 100(9), 3594-3601.
[http://dx.doi.org/10.1002/jps.22639] [PMID: 21618241]
[112]
Yu, J.; Tang, L.; Yang, Y.; Ji, R. Synthesis and evaluation of a series of benzopyran derivatives as PPAR α/γ agonists. Eur. J. Med. Chem., 2008, 43(11), 2428-2435.
[http://dx.doi.org/10.1016/j.ejmech.2008.01.029] [PMID: 18329751]
[113]
Nazreen, S.; Alam, M.S.; Hamid, H.; Yar, M.S.; Shafi, S.; Dhulap, A.; Alam, P.; Pasha, M A Q.; Bano, S.; Alam, M.M.; Haider, S.; Ali, Y.; Kharbanda, C.; Pillai, K.K. Design, synthesis, in silico molecular docking and biological evaluation of novel oxadiazole based thiazolidine-2,4-diones bis-heterocycles as PPAR-γ agonists. Eur. J. Med. Chem., 2014, 87, 175-185.
[http://dx.doi.org/10.1016/j.ejmech.2014.09.010] [PMID: 25255433]
[114]
Piemontese, L.; Fracchiolla, G.; Carrieri, A.; Parente, M.; Laghezza, A.; Carbonara, G.; Sblano, S.; Tauro, M.; Gilardi, F.; Tortorella, P.; Lavecchia, A.; Crestani, M.; Desvergne, B.; Loiodice, F. Design, synthesis and biological evaluation of a class of bioisosteric oximes of the novel dual peroxisome proliferator-activated receptor α/γ ligand LT175. Eur. J. Med. Chem., 2015, 90, 583-594.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.044] [PMID: 25497132]
[115]
Choi, J.; Ko, Y.; Lee, H.S.; Park, Y.S.; Yang, Y.; Yoon, S. Identification of (β-carboxyethyl)-rhodanine derivatives exhibiting peroxisome proliferator-activated receptor γ activity. Eur. J. Med. Chem., 2010, 45(1), 193-202.
[http://dx.doi.org/10.1016/j.ejmech.2009.09.042] [PMID: 19879669]
[116]
Piemontese, L.; Cerchia, C.; Laghezza, A.; Ziccardi, P.; Sblano, S.; Tortorella, P.; Iacobazzi, V.; Infantino, V.; Convertini, P.; Dal Piaz, F.; Lupo, A.; Colantuoni, V.; Lavecchia, A.; Loiodice, F. New diphenylmethane derivatives as peroxisome proliferator-activated receptor alpha/gamma dual agonists endowed with anti-proliferative effects and mitochondrial activity. Eur. J. Med. Chem., 2017, 127, 379-397.
[http://dx.doi.org/10.1016/j.ejmech.2016.12.047] [PMID: 28076827]
[117]
Furukawa, A.; Arita, T.; Fukuzaki, T.; Mori, M.; Honda, T.; Satoh, S.; Matsui, Y.; Wakabayashi, K.; Hayashi, S.; Nakamura, K.; Araki, K.; Kuroha, M.; Tanaka, J.; Wakimoto, S.; Suzuki, O.; Ohsumi, J. Synthesis and biological evaluation of novel (-)-cercosporamide derivatives as potent selective PPARγ modulators. Eur. J. Med. Chem., 2012, 54, 522-533.
[http://dx.doi.org/10.1016/j.ejmech.2012.05.040] [PMID: 22727448]
[118]
Shi, G.Q.; Dropinski, J.F.; McKeever, B.M.; Xu, S.; Becker, J.W.; Berger, J.P.; MacNaul, K.L.; Elbrecht, A.; Zhou, G.; Doebber, T.W.; Wang, P.; Chao, Y.S.; Forrest, M.; Heck, J.V.; Moller, D.E.; Jones, A.B. Design and synthesis of α-aryloxyphenylacetic acid derivatives: a novel class of PPARalpha/γ dual agonists with potent antihyperglycemic and lipid modulating activity. J. Med. Chem., 2005, 48(13), 4457-4468.
[http://dx.doi.org/10.1021/jm0502135] [PMID: 15974597]
[119]
Ohashi, M.; Nakagome, I.; Kasuga, J.; Nobusada, H.; Matsuno, K.; Makishima, M.; Hirono, S.; Hashimoto, Y.; Miyachi, H. Design, synthesis and in vitro evaluation of a series of α-substituted phenylpropanoic acid PPARγ agonists to further investigate the stereochemistry-activity relationship. Bioorg. Med. Chem., 2012, 20(21), 6375-6383.
[http://dx.doi.org/10.1016/j.bmc.2012.08.061] [PMID: 23022278]
[120]
Dixit, V.A.; Rathi, P.C.; Bhagat, S.; Gohlke, H.; Petersen, R.K.; Kristiansen, K.; Chakraborti, A.K.; Bharatam, P.V. Design and synthesis of novel Y-shaped barbituric acid derivatives as PPARγ activators. Eur. J. Med. Chem., 2016, 108, 423-435.
[http://dx.doi.org/10.1016/j.ejmech.2015.11.030] [PMID: 26708109]
[121]
Bajare, S.; Anthony, J.; Nair, A.; Marita, R.; Damre, A.; Patel, D.; Rao, C.; Sivaramakrishnan, H.; Deka, N. Synthesis of N-(5-chloro-6-(quinolin-3-yloxy)pyridin-3-yl)benz-enesulfonamide derivatives as non-TZD peroxisome proliferator-activated receptor γ (PPARγ) agonist. Eur. J. Med. Chem., 2012, 58, 355-360.
[http://dx.doi.org/10.1016/j.ejmech.2012.10.027] [PMID: 23142675]
[122]
Tyagi, S.; Gupta, P.; Saini, A.S.; Kaushal, C.; Sharma, S. The peroxisome proliferator-activated receptor: a family of nuclear receptors role in various diseases. J. Adv. Pharm. Technol. Res., 2011, 2(4), 236-240.
[http://dx.doi.org/10.4103/2231-4040.90879] [PMID: 22247890]
[123]
Celi, F.S.; Shuldiner, A.R. The role of peroxisome proliferator-activated receptor gamma in diabetes and obesity. Curr. Diab. Rep., 2002, 2(2), 179-185.
[http://dx.doi.org/10.1007/s11892-002-0078-2] [PMID: 12643137]
[124]
Green, S. PPAR: a mediator of peroxisome proliferator action. Mut. Res, 333(1-2), 101-109.
[http://dx.doi.org/10.1016/0027-5107(95)00136-0] [PMID: 8538617]

Rights & Permissions Print Cite
Article Metrics
79
2
© 2024 Bentham Science Publishers | Privacy Policy