Peroxisome proliferator-activated receptors and their ligands: Nutritional and clinical implications - A review

Nutrition Journal

Volumn 13, Issue 1, 2014, Pages

  Grygiel Górniak, Bogna ^a  

^a POZNAN UNIVERSITY OF MEDICAL SCIENCES   (Poland)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ANTICOAGULANT AGENT; ANTIHYPERTENSIVE AGENT; CHOLESTEROL; CIGLITAZONE; CLOFIBRATE; EFATUTAZONE; ESSENTIAL FATTY ACID; FARGLITAZAR; FENOFIBRATE; GEMFIBROZIL; ICOSANOID; PALMIDROL; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; PHYTANIC ACID; ROSIGLITAZONE; TROGLITAZONE; [2 METHYL 4 [4 METHYL 2 (4 TRIFLUOROMETHYLPHENYL) 5 THIAZOLYLMETHYLTHIO]PHENOXY]ACETIC ACID; LIGAND; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; RETINOID X RECEPTOR;

ADIPOCYTE; ADIPOGENESIS; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CHOLESTEROL BLOOD LEVEL; DIABETES MELLITUS; DYSLIPIDEMIA; FATTY ACID METABOLISM; FATTY ACID OXIDATION; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; HEART MUSCLE; HUMAN; LIPID DIET; LIPID STORAGE; LIPOGENESIS; NONHUMAN; NUTRITIONAL ASSESSMENT; OBESITY; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN STRUCTURE; AGONISTS; ANIMAL; DRUG EFFECTS; GENETIC TRANSCRIPTION; PHYSIOLOGY;

ANIMALS; HUMANS; LIGANDS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; PPAR ALPHA; PPAR DELTA; PPAR GAMMA; PPAR-BETA; RETINOID X RECEPTORS; TRANSCRIPTION, GENETIC;

EID: 84893794489     PISSN: None     EISSN: 14752891     Source Type: Journal    
DOI: 10.1186/1475-2891-13-17     Document Type: Article

References (83)

1. The mechanisms of action of PPARs. Berger J, Moller DE, Annu Rev Med 2002 53 409 435 10.1146/annurev.med.53.082901.104018 11818483
2. Advances in understanding the regulation of apoptosis and mitosis by peroxisome-proliferator activated receptors in pre-clinical models: relevance for human health and disease. Boitier E, Gautier JC, Roberts R, Comp Hepatol 2003 2 1 3 10.1186/1476-5926-2-3 12622871
3. Comparative gene expression profiles induced by PPARγ and PPARα/γ agonists in human hepatocytes. Rogue A, Lambert C, Jossé R, Antherieu S, Spire C, Claude N, Guillouzo A, PLoS One 2011 6 4 18816 10.1371/journal.pone.0018816 21533120
4. Gene expression changes induced by PPAR gamma agonists in animal and human liver. Rogue A, Spire C, Brun M, Claude N, Guillouzo A, PPAR Res 2010 2010 325183 20981297
5. The PPARs: from orphan receptors to drug discovery. Willson TM, Brown PJ, Sternbach DD, Henke BR, J Med Chem 2000 43 527 550 10.1021/jm990554g 10691680
6. Coactivators in PPAR-regulated gene expression. Viswakarma N, Jia Y, Bai L, Vluggens A, Borensztajn J, Xu J, Reddy JK, PPAR Res 2010 2010 2050126
7. PPARγ in human and mouse physiology. Heikkinen S, Auwerx J, Argmann CA, Biochim Biophys Acta 2007 1771 8 999 1013 10.1016/j.bbalip.2007.03.006 17475546
8. From molecular action to physiological outputs:peroxisome proliferator-activated receptors are nuclearreceptors at the crossroads of key cellular functions. Feige JN, Gelman L, Michalik L, Desvergne B, Wahli W, Prog Lipid Res 2006 45 2 120 159 10.1016/j.plipres.2005.12.002 16476485
9. PPARgamma knockdown by engineered transcription factors: exogenous PPARgamma2 but not PPARgamma1 reactivates adipogenesis. Ren D, Collingwood TN, Rebar EJ, Wolffe AP, Camp HS, Genes Dev 2002 16 1 27 32 10.1101/gad.953802 11782442
10. Ligand-independent activation domain in the N terminus of peroxisome proliferator-activated receptor gamma (PPARgamma). Differential activity of PPARgamma1 and -2 isoforms and influence of insulin. Werman A, Hollenberg A, Solanes G, Bjorbaek C, Vidal-Puig AJ, Flier JS, J Biol Chem 1997 272 32 20230 20235 10.1074/jbc.272.32.20230 9242701
11. Present concepts and future outlook: function of peroxisome proliferator-activated receptors (PPARs) for pathogenesis, progression, and therapy of cancer. Sertznig P, Seifert M, Tilgen W, Reichrath J, J Cell Physiol 2007 212 1 1 12 10.1002/jcp.20998 17443682
12. n-3 Fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator-activated receptor-alpha-dependent manner. Neschen S, Morino K, Dong J, Wang-Fischer Y, Cline GW, Romanelli AJ, Rossbacher JC, Moore IK, Regittnig W, Munoz DS, Kim JH, Shulman GI, Diabetes 2007 56 4 1034 1041 10.2337/db06-1206 17251275
13. Oxidized phospholipids activate PPARalpha in a phospholipase A2-dependent manner. Delerive P, Furman C, Teissier E, Fruchart J, Duriez P, Staels B, FEBS Lett 2000 471 1 34 38 10.1016/S0014-5793(00)01364-8 10760508
14. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator- activated receptors alpha and gamma. Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, Koble CS, Devchand P, Whali W, Willson TM, Lenhard JM, Lehmann JM, Proc Natl Acad Sci U S A 1997 94 9 4318 4323 10.1073/pnas.94.9.4318 9113987
15. The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide. Lo Verme J, Fu J, Astarita G, La Rana G, Russo R, Calignano A, Piomelli D, Mol Pharmacol 2005 67 1 15 19 10.1124/mol.104.006353 15465922
16. Exploring the binding site structure of the PPAR gamma ligand-binding domain by computational solvent mapping. Sheu SH, Kaya T, Waxman DJ, Vajda S, Biochemistry (Mosc) 2005 44 4 1193 1209 10.1021/bi048032c
17. The many faces of PPARgamma. Lehrke M, Lazar MA, Cell 2005 123 6 993 999 10.1016/j.cell.2005.11.026 16360030
18. PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. Medina-Gomez G, Gray SL, Yetukuri L, Shimomura K, Virtue S, Campbell M, Curtis RK, Jimenez-Linan M, Blount M, Yeo GSH, Lopez M, Seppänen-Laakso T, Ashcroft FM, Orešič M, Vidal-Puig A, PLoS Genet 2007 3 4 64 10.1371/journal.pgen.0030064 17465682
19. Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Kang H, Evans RM, Cell 2003 113 2 159 170 10.1016/S0092-8674(03)00269-1 12705865
20. Activation of peroxisome proliferator-activated receptor delta stimulates the proliferation of human breast and prostate cancer cell lines. Stephen RL, Gustafsson MC, Jarvis M, Tatoud R, Marshall BR, Knight D, Ehrenborg E, Harris AL, Wolf CR, Palmer CN, Cancer Res 2004 64 9 3162 3170 10.1158/0008-5472.CAN-03- 2760 15126355
21. Prevention/reversal of choline deficiency-induced steatohepatitis by a peroxisomeproliferator-activated receptor alpha ligand in rats. Rao MS, Kashireddy P, Musunuri S, Okonkwo A, In Vivo 2002 16 2 145 152 12073774
22. Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Krey G, Braissant O, L'Horset F, Kalkhoven E, Perroud M, Parker MG, Wahli W, Mol Endocrinol 1997 11 6 779 791 10.1210/mend.11.6.0007 9171241
23. Peroxisome proliferator activated receptor-gamma (PPAR-gamma) ligands and angiogenesis. Margeli A, Kouraklis G, Theocharis S, Angiogenesis 2003 6 3 165 169 15041792
24. Peroxisome proliferator-activated receptors in vascular biology and atherosclerosis: emerging insights for evolving paradigms. Plutzky J, Curr Atheroscler Rep 2000 2 4 327 335 10.1007/s11883-000-0067-3 11122762
25. Fish oil consumption and mortality from coronary heart disease. Bang JO, Dyberg J, N Engl J Med 1985 313 822 823
26. Effects of bezafibrate on insulin sensitivity and insulin secretion in non-obese Japanese type 2 diabetic patients. Taniguchi A, Fukushima M, Sakai M, Tokuyama K, Nagata I, Fukunaga A, Kishimoto H, Doi K, Yamashita Y, Matsuura T, Kitatani N, Okumura T, Nagasaka S, Nakaishi S, Nakai Y, Metabolism 2001 50 4 477 480 10.1053/meta.2001.21028 11288046
27. Rosiglitazone improves blood pressure in patients with type 2 diabetes mellitus. Bakris GL, Dole JF, Porter LE, Huang C, Freed MI, Diabetes 2000 49 suppl 1 96
28. Comparative effects of pioglitazone, glibenclamide, and voglibose on urinary endothelin-1 and albumin excretion in diabetes patients. Nakamura T, Ushiyama C, Shimada N, Hayashi K, Ebihara I, Koide H, J Diabetes Complications 2000 14 5 250 254 10.1016/S1056-8727(00)00124-0 11113686
29. The role of fibric acids in atherosclerosis. Fruchart JC, Staels B, Duriez P, Curr Atheroscler Rep 2001 3 1 83 92 10.1007/s11883-001-0015-x 11123853
30. Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis. Volker D, Fitzgerald P, Major G, Garg M, J Rheumatol 2000 27 10 2343 2346 11036827
31. Oxidized omega-3 fatty acids in fish oil inhibit leukocyte-endothelial interactions through activation of PPAR alfa. Sethi S, Ziouzenkova O, Ni H, Wagner DD, Plutzky J, Mayadas TN, Blood 2002 100 4 1340 1346 10.1182/blood-2002-01-0316 12149216
32. PPAR alpha in the pathogenesis of fatty liver disease. Rao MS, Reddy JK, Hepatology 2004 40 4 783 786 10.1002/hep.20453 15382158
33. Histopathology of pediatric nonalcoholic fatty liver disease. Schwimmer JB, Behling C, Newbury R, Deutsch R, Nievergelt C, Schork NJ, Lavine JE, Hepatology 2005 42 3 641 649 10.1002/hep.20842 16116629
34. Central role of PPARalpha-dependent hepatic lipid turnover in dietary steatohepatitis in mice. Ip E, Farrell GC, Robertson G, Hall P, Kirsch R, Leclercq I, Hepatology 2003 38 1 123 132 10.1053/jhep.2003.50307 12829994
35. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Kris-Etherton PM, Harris WS, Appel LJ, Circulation 2002 106 21 2747 2757 10.1161/01.CIR.0000038493.65177.94 12438303
36. Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Diabetes Atherosclerosis Intervention Study Investigators, Lancet 2001 357 9260 905 910 11289345
37. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, Forder P, Pillai A, Davis T, Glasziou P, Drury P, Kesäniemi YA, Sullivan D, Hunt D, Colman P, d'Emden M, Whiting M, Ehnholm C, Laakso M, FIELD study investigators, Lancet 2005 366 9500 1849 1861 16310551
38. Effects of combination lipid therapy in type 2 diabetes mellitus. Ginsberg HN, Elam MB, Lovato LC, Crouse JR 3rd, Leiter LA, Linz P, Friedewald WT, Buse JB, Gerstein HC, Probstfield J, Grimm RH, Ismail-Beigi F, Bigger JT, Goff DC Jr, Cushman WC, Simons-Morton DG, Byington RP, ACCORD Study Group, N Engl J Med 2010 362 17 1563 1574 20228404
39. Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. Davis TM, Ting R, Best JD, Donoghoe MW, Drury PL, Sullivan DR, Jenkins AJ, O'Connel RL, Whiting MJ, Glasziou PP, Simes RJ, Kesäniemi YA, Gebski VJ, Scott RS, Keech AC, Fenofibrate Intervention and Event Lowering in Diabetes Study investigators, Diabetologia 2011 54 2 280 290 10.1007/s00125-010-1951-1 21052978
40. Effects of long-term fenofibrate treatment on markers of renal function in type 2 diabetes: the FIELD Helsinki substudy. Forsblom C, Hiukka A, Leinonen ES, Sundvall J, Groop PH, Taskinen MR, Diabetes Care 2010 33 2 215 220 10.2337/dc09-0621 19846798
41. Fenofibrate increases creatininemia by increasing metabolic production of creatinine. Hottelart C, El Esper N, Rose F, Achard JM, Fournier A, Nephron 2002 92 3 536 541 10.1159/000064083 12372935
42. Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. Berger J, Leibowitz MD, Doebber TW, Elbrecht A, Zhang B, Zhou G, Biswas C, Cullinan CA, Hayes NS, Li Y, Tanen M, Ventre J, Wu MS, Berger GD, Mosley R, Marquis R, Santini C, Sahoo SP, Tolman RL, Smith RG, Moller DE, J Biol Chem 1999 274 10 6718 6725 10.1074/jbc.274.10.6718 10037770
43. A new, highly selective marine peroxisome proliferator-activated receptor delta agonist increases responsiveness to thermogenic stimuli and glucose uptake in skeletal muscle in obese mice. Ngala RA, Stocker CJ, Roy AG, Hislop D, Wargent E, Bell R, Hassall DG, Harling JD, Billin AN, Willson TM, Arch JR, Cawthorne MA, Diab Obes Metab 2011 13 5 455 464 10.1111/j.1463-1326.2011.01371.x
44. Nuclear receptors PPAR beta/delta and PPAR alpha direct distinct metabolic regulatory programs in the mouse heart. Burkart EM, Sambandam N, Han X, Gross RW, Courtois M, Gierasch CM, Shoghi K, Welch MJ, Kelly DP, J Clin Invest 2007 117 12 3930 3939 18037994
45. Decrease of peroxisome proliferator-activated receptor delta expression in cardiomyopathy of streptozotocin-induced diabetic rats. Yu BC, Chang CK, Ou HY, Cheng KC, Cheng JT, Cardiovasc Res 2008 80 1 78 87 10.1093/cvr/cvn172 18573863
46. PPAR delta functions as a prostacyclin receptor in blastocyst implantation. Lim H, Dey SK, Trends Endocrinol Metab 2000 11 4 137 142 10.1016/S1043-2760(00)00243-5 10754535
47. Peroxisome-proliferator-activated receptors and cancers: complex stories. Michalik L, Desvergne B, Wahli W, Nat Rev Cancer 2004 4 1 61 70 10.1038/nrc1254 14708026
48. Peroxisome proliferator-activated receptor alpha/gamma dual agonists for the treatment of type 2 diabetes. Henke BR, J Med Chem 2004 47 17 4118 4127 10.1021/jm030631e 15293980
49. PPARγmediated insulin sensitization: the importance of fat versus muscle. Kintscher U, Law RE, Am J Physiol Endocrinol Metab 2005 288 2 287 E291 10.1152/ajpendo.00440.2004 15637349
50. PPARgamma activation in human endothelial cells increases plasminogen activator inhibitor type-1 expression: PPARgamma as a potential mediator in vascular disease. Marx N, Bourcier T, Sukhova GK, Libby P, Plutzky J, Arterioscler Thromb Vasc Biol 1999 19 3 546 551 10.1161/01.ATV.19.3.546 10073956
51. PPARgamma as a therapeutic target for tumor angiogenesis and metastasis. Panigrahy D, Huang S, Kieran MW, Kaipainen A, Cancer Biol Ther 2005 4 7 687 693 10.4161/cbt.4.7.2014 16082179
52. Prospects for prevention and treatment of cancer with selective PPARγ modulators (SPARMs). Sporn MB, Suh N, Mangelsdorf DJ, Trends Mol Med 2001 7 9 395 400 10.1016/S1471-4914(01)02100-1 11530334
53. Arachidonic and docosahexaenoic acids reduce the growth of A549 human lung-tumor cells increasing lipid peroxidation and PPARs. Trombetta A, Maggiora M, Martinasso G, Cotogni P, Canuto RA, Muzio G, Chem Biol Interact 2007 165 3 239 250 10.1016/j.cbi.2006.12.014 17275799
54. Differential effects of delivery of omega-3 fatty acids to human cancer cells by low-density lipoproteins versus albumin. Edwards IJ, Berquin IM, Sun H, O'Flaherty JT, Daniel LW, Thomas MJ, Rudel LL, Wykle RL, Chen YQ, Clin Cancer Res 2004 10 24 8275 8283 10.1158/1078-0432.CCR-04-1357 15623603
55. Omega-3 polyunsaturated fatty acids regulate syndecan-1 expression in human breast cancer cells. Sun H, Berquin IM, Edwards IJ, Cancer Res 2005 65 10 4442 4447 10.1158/0008-5472.CAN-04-4200 15899837
56. Peroxisome proliferator-activated receptor γ-mediated up-regulation of syndecan-1 by n-3 fatty acids promotes apoptosis of human breast cancer cells. Sun H, Berquin IM, Owens RT, O'Flaherty JT, Edwards IJ, Cancer Res 2008 68 8 2912 2919 10.1158/0008-5472.CAN-07-2305 18413760
57. Dietary supplementation with long-chain monounsaturated fatty acids attenuates obesity-related metabolic dysfunction and increases expression of PPAR gamma in adipose tissue in type 2 diabetic KK-Ay mice. Yang ZH, Miyahara H, Iwasaki Y, Takeo J, Katayama M, Nutr Metab (Lond) 2013 10 1 16 10.1186/1743-7075-10-16 23360495
58. Oxidized omega-3 fatty acids inhibit NF-κB activation via a PPARα-dependent pathway. Mishra A, Chaudhary A, Sethi S, Arterioscler Thromb Vasc Biol 2004 24 9 1621 1627 10.1161/01.ATV.0000137191.02577.86 15231516
59. Peroxisome proliferator-activated receptor alpha in the human breast cancer cell lines MCF-7 and MDA-MB-231. Suchanek KM, May FJ, Robinson JA, Lee WJ, Holman NA, Monteith GR, Roberts-Thomson SJ, Mol Carcinog 2002 34 4 165 171 10.1002/mc.10061 12203367
60. Phytanic acid, a natural peroxisome proliferator-activated receptor (PPAR) agonist, regulates glucose metabolism in rat primary hepatocytes. Heim M, Johnson J, Boess F, Bendik I, Weber P, Hunziker W, Fluhmann B, FASEB J 2002 16 7 718 720 11923221
61. Ligands for peroxisome proliferator-activated receptor γ and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Elstner E, Muller C, Koshizuka K, Williamson EA, Park D, Asou H, Shintaku P, Said JW, Heber D, Koeffler HP, Proc Natl Acad Sci U S A 1998 95 15 8806 8811 10.1073/pnas.95.15.8806 9671760
62. Current treatment of insulin resistance in type 2 diabetes mellitus. Tan MH, Int J Clin Pract Suppl 2000 113 54 62 11965833
63. Pioglitazone versus rosiglitazone: effects on lipids, lipoproteins, and apolipoproteins in head-to-head randomized clinical studies. Deeg MA, Tan MH, PPAR Res 2008 2008 520465 18769492
64. Thiazolidinediones: a 2010 perspective. Krishnaswami A, Ravi-Kumar S, Lewis JM, Perm J 2010 14 3 64 72
65. Evolution of peroxisome proliferator-activated receptor agonists. Chang F, Jaber LA, Berlie HD, O'Connell MB, Ann Pharmacother 2007 41 6 973 983 10.1345/aph.1K013 17519293
66. Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled dose-response study. The Pioglitazone 001 Study Group. Aronoff S, Rosenblatt S, Braithwaite S, Egan JW, Mathisen AL, Schneider RL, Diabetes Care 2000 23 11 1605 1611 10.2337/diacare.23.11.1605 11092281
67. Rosiglitazone short-term monotherapy lowers fasting and post-prandial glucose in patients with type II diabetes. Raskin P, Rappaport EB, Cole ST, Yan Y, Patwardhan R, Freed MI, Diabetologia 2000 43 3 278 284 10.1007/s001250050045 10768088
68. Safety and tolerability of pioglitazone in high-risk patients with type 2 diabetes: an overview of data from PROactive. Dormandy J, Bhattacharya M, Van Troostenburg de Bruyn AR, Drug Saf 2009 32 3 187 202 10.2165/00002018-200932030- 00002 19338377
69. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. Nissen SE, Wolski K, N Engl J Med 2007 356 24 2457 2471 10.1056/NEJMoa072761 17517853
70. Impact of adjunctive thiazolidinedione therapy on blood lipid levels and glycemic control in patients with type 2 diabetes. Peters Harmel AL, Kendall DM, Buse JB, Boyle PJ, Marchetti A, Lau H, Curr Med Res Opin 2004 20 2 215 223 10.1185/030079903125002937 15006017
71. Thiazolidinediones in type 2 diabetes mellitus: current clinical evidence. Diamant M, Heine RJ, Drugs 2003 63 13 1373 1405 10.2165/00003495- 200363130-00004 12825962
72. The effects of troglitazone, an insulin-sensitizing agent, on the endothelial function in early and late type 2 diabetes: a placebo-controlled randomized clinical trial. Caballero A, Saouaf R, Lim SC, Hamdy O, Abou-Elenin K, O'Connor C, LoGerfo FW, Horton ES, Veves A, Metabolism 2003 52 2 173 180 10.1053/meta.2003.50023 12601628
73. PPARgamma activation, by reducing oxidative stress, increases NO bioavailability in coronary arterioles of mice with Type 2 diabetes. Bagi Z, Koller A, Kaley G, Am J Physiol Heart Circ Physiol 2004 286 2 742 H748 10.1152/ajpheart.00718.2003 14551045
74. Reactivation of suppressed RhoB is a critical step for the inhibition of anaplastic thyroid cancer growth. Marlow LA, Reynolds LA, Cleland AS, Cooper SJ, Gumz ML, Kurakata S, Fujiwara K, Zhang Y, Sebo T, Grant C, McIver B, Wadsworth JT, Radisky DC, Smallridge RC, Copland JA, Cancer Res 2009 69 4 1536 1544 10.1158/0008-5472.CAN-08-3718 19208833
75. The safety of thiazolidinediones. Tolman KG, Expert Opin Drug Saf 2011 10 3 419 428 10.1517/14740338.2011.534982 21366501
76. Safety issues and prospects for future generations of PPAR modulators. Rubenstrunk A, Hanf R, Hum DW, Fruchart JC, Staels B, Biochim Biophys Acta 2007 1771 8 1065 1081 10.1016/j.bbalip.2007.02.003 17428730
77. S 26948: a new specific peroxisome proliferator activated receptor gamma modulator with potent antidiabetes and antiatherogenic effects. Carmona MC, Louche K, Lefebvre B, Pilon A, Hennuyer N, Audinot-Bouchez V, Fievet C, Torpier G, Formstecher P, Renard P, Lefebvre P, Dacquet C, Staels B, Casteilla L, Pénicaud L, Consortium of the French Ministry of Research and Technology, Diabetes 2007 56 11 2797 2808 10.2337/db06-1734 17704298
78. Selective modulation of PPARgamma activity can lower plasma glucose without typical thiazolidinedione side-effects in patients with Type 2 diabetes. Dunn FL, Higgins LS, Fredrickson J, DePaoli AM, J Diabetes Complicat 2011 25 3 151 158 10.1016/j.jdiacomp.2010.06.006 20739195
79. Antineoplastic effects of peroxisome proliferator-activated receptor gamma agonists. Grommes C, Landreth GE, Heneka MT, Lancet Oncol 2004 5 7 419 429 10.1016/S1470-2045(04)01509-8 15231248
80. Urothelial carcinogenesis in the urinary bladder of rats treated with naveglitazar, a gamma-dominant PPAR alpha/gamma agonist: lack of evidence for urolithiasis as an inciting event. Long GG, Reynolds VL, Lopez-Martinez A, Ryan TE, White SL, Eldridge SR, Toxicol Pathol 2008 36 2 218 231 10.1177/ 0192623307311757 18474944
81. Tesaglitazar, as add-on therapy to sulphonylurea, dose-dependently improves glucose and lipid abnormalities in patients with type 2 diabetes. Wilding JP, Gause-Nilsson I, Persson A, Diab Vasc Dis Res 2007 4 3 194 203 17907109
82. Effect of muraglitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus. Nissen SE, Wolski K, Topol EJ, JAMA 2005 294 20 2581 2586 10.1001/jama.294.20.joc50147 16239637
83. Effect of the dual peroxisome proliferator-activated receptor-alpha/gamma agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): a phase II, randomised, dose-ranging study. Henry RR, Lincoff AM, Mudaliar S, Rabbia M, Chognot C, Herz M, Lancet 2009 374 9684 126 135 10.1016/S0140-6736(09)60870-9 19515415