Peroxisome proliferator-activated receptor (PPAR) in metabolic syndrome and type 2 diabetes mellitus

Current Diabetes Reviews

Volumn 3, Issue 1, 2007, Pages 33-39

  Jay, Mollie A ^a   Ren, Jun ^a  

^a UNIVERSITY OF WYOMING   (United States)

Author keywords

Cardiovascular; Diabetes; Lipid and glucose metabolism; Metabolic syndrome; PPAR

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; 3 [4 [3 (4 CHLORO 2 PHENOXYPHENOXY)BUTOXY] 2 ETHYLPHENYL]PROPIONIC ACID; BEZAFIBRATE; FATTY ACID; FENOFIBRATE; FIBRIC ACID DERIVATIVE; GEMFIBROZIL; GLUCOSE; HEMOGLOBIN A1C; LIGAND; LIPID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PIOGLITAZONE; PLACEBO; RECEPTOR SUBTYPE; ROSIGLITAZONE; UNCLASSIFIED DRUG;

ABDOMINAL OBESITY; ATHEROSCLEROTIC PLAQUE; BLOOD CLOTTING; BLOOD PRESSURE REGULATION; CARDIOVASCULAR RISK; CLINICAL TRIAL; DRUG COST; DRUG INDICATION; DRUG SAFETY; DRUG TARGETING; DRUG USE; DYSLIPIDEMIA; ENDOTHELIUM; EPIDEMIC; FATTY ACID OXIDATION; FATTY ACID TRANSPORT; GLUCOSE OXIDATION; GLUCOSE TRANSPORT; HEART DISEASE; HUMAN; HYPERGLYCEMIA; HYPERTENSION; INSULIN RESISTANCE; LIFESTYLE MODIFICATION; LIPID METABOLISM; LIPID TRANSPORT; METABOLIC SYNDROME X; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; RISK MANAGEMENT;

ANIMALS; ANTI-INFLAMMATORY AGENTS; DIABETES MELLITUS, TYPE 2; GLUCOSE; HUMANS; HYPOGLYCEMIC AGENTS; INFLAMMATION; LIPID METABOLISM; METABOLIC SYNDROME X; PANCREAS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS;

EID: 34247155688     PISSN: 15733998     EISSN: None     Source Type: Journal    
DOI: 10.2174/157339907779802067     Document Type: Review

References (82)

1. Licata G, Argano C, Di Chiara T, Parrinello G, Scaglione R. Obesity: a main factor of metabolic syndrome? Panminerva Med 2006; 48(2): 7-85.
2. Bassuk SS, Manson JE. Epidemiological evidence for the role of physical activity in reducing risk of type 2 diabetes and cardiovascular disease. J Appl Physiol 2005; 99(3): 1193-1204.
3. Weindl G, Schafer-Korting M, Schaller M, Korting HC. Peroxisome proliferator-activated receptors and their ligands: entry into the post-glucocorticoid era of skin treatment? Drugs 2005; 65(14): 1919-1934.
4. Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 1990; 347(6294): 645-650.
5. Privalsky ML. The role of corepressors in transcriptional regulation by nuclear hormone receptors. Annu Rev Physiol 2004; 66: 315-360.
6. Semple RK, Chatterjee VK, O'rahilly S. PPAR gamma and human metabolic disease. J Clin Invest 2006; 116(3): 581-589.
7. Omi T, Brenig B, Spilar KS, Iwamoto S, Stranzinger G, Neuenschwander S. Identification and characterization of novel peroxisome proliferator-activated receptor-gamma (PPAR-gamma) transcriptional variants in pig and human. J Anim Breed Genet 2005; 122 Suppl 1: 45-53.
8. Lefebvre P, Chinetti G, Fruchart JC, Staels B. Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. J Clin Invest 2006; 116(3): 571-580.
9. Nomura M, Tanase T, Ide T, et al. Design, synthesis, and evaluation of substituted phenylpropanoic acid derivatives as human peroxisome proliferator activated receptor activators. Discovery of potent and human peroxisome proliferator activated receptor alpha subtype-selective activators. J Med Chem 2003; 46(17): 3581-3599.
10. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999; 341(6): 410-418.
11. Diabetes Atherosclerosis Intervention Study Ivestigators. Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet 2001; 357(9260): 905-910.
12. Keech A, Simes RJ, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005; 366(9500): 1849-1861.
13. Verges B. Fenofibrate therapy and cardiovascular protection in diabetes: recommendations after FIELD. Curr Opin Lipidol 2006; 17(6): 653-658.
14. Cheng L. Ding G, Qin Q, et al. Cardiomyocyte-restricted peroxisome proliferator-activated receptor-delta deletion perturbs myocardial fatty acid oxidation and leads to cardiomyopathy. Nat Med 20134; 10(11): 1245-1250.
15. Roduit R, Morin J, Masse F, et al. Glucose down-regulates the expression of the peroxisome proliferator-activated receptor-alpha gene in the pancreatic beta -cell. J Biol Chem 2000; 275(46): 35799-35806.
16. Takahashi S, Tanaka T, Kodama T, Sakai J. Peroxisome proliferator-activated receptor delta (PPARdelta), a novel target site for drug discovery in metabolic syndrome. Pharmacol Res 2006; 53(6): 501-507.
17. Blanquart C, Barbier O, Fruchart JC, Staels B, Glineur C. Peroxisome proliferator-activated receptor alpha (PPARalpha) turnover by the ubiquitin-proteasome system controls the ligand-induced expression level of its target genes. J Biol Chem 2002; 277(40): 37254-37259.
18. Chinetti G, Gbaguidi FG, Griglio S, et al. CLA-1/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferator-activated receptors. Circulation 2000; 101(20): 2411-2417.
19. Chinetti G, Lestavel S, Bocher V, et al. PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med 2001; 7(1): 53-58.
20. Gervois P, Torra IP, Fruchart JC, Staels B. Regulation of lipid and lipoprotein metabolism by PPAR activators. Clin Chem Lab Med 2000; 38(1): 3-11.
21. Lee CH, Kang K, Mehl IR, et al. Peroxisome proliferator-activated receptor delta promotes very low-density lipoprotein-derived fatty acid catabolism in the macrophage. Proc Natl Acad Sci USA 2006; 103(7): 2434-2439.
22. Lie J, Lankhuizen IM, Gross B, et al. Fenofibrate reverses the decline in HDL cholesterol in mice overexpressing human phospholipid transfer protein. Biochim Biophys Acta 2005; 1738(1-3): 48-53.
23. Rubic T, Lorenz RL. Downregulated CD36 and oxLDL uptake and stimulated ABCA1/G1 and cholesterol efflux as anti-athero-sclerotic mechanisms of interleukin-10. Cardiovasc Res 2006; 69(2): 527-535.
24. Brandt JM, Djouadi F, Kelly DP. Fatty acids activate transcription of the muscle carnitine palmitoyltransferase I gene in cardiac myocytes via the peroxisome proliferator-activated receptor alpha. J Biol Chem 1998; 273(37): 23786-23792.
25. Lee CH, Olson P, Hevener A, et al. PPARdelta regulates glucose metabolism and insulin sensitivity. Proc Natl Acad Sci U S A 2006; 103(9): 3444-3449.
26. Fruchart JC. Peroxisome proliferator-activated receptor-alpha activation and high-density lipoprotein metabolism. Am J Cardiol 2001; 88(12A): 24N-29N.
27. Panzenboeck U, Kratzer I, Sovic A, et al. Regulatory effects of synthetic liver X receptor- and peroxisome-proliferator activated receptor agonists on sterol transport pathways in polarized cerebrovascular endothelial cells. Int J Biochem Cell Biol 2006; 38(8): 1314-1329.
28. Schmitz G, Langmann T. Transcriptional regulatory networks in lipid metabolism control ABCA1 expression. Biochim Biophys Acta 2005; 1735(1): 1-19.
29. Luquet S, Gaudel C, Holst D, et al. Roles of PPAR delta in lipid absorption and metabolism: a new target for the treatment of type 2 diabetes. Biochim Biophys Acta 2005; 1740(2): 313-317.
30. Planavila A, Laguna JC, Vazquez-Carrera M. Nuclear factor-kappaB activation leads to down-regulation of fatty acid oxidation during cardiac hypertrophy. J Biol Chem 2005; 280(17): 17464-17471.
31. Oliver WR, Jr., Shenk JL, Snaith MR, et al. A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport. Proc Natl Acad Sci U S A 2001; 98(9): 5306-5311.
32. van der Veen JN, Kruit JK, Havinga R, et al. Reduced cholesterol absorption upon PPARdelta activation coincides with decreased intestinal expression of NPC1L1. J Lipid Res 2005; 46(3): 526-534.
33. Henson P. Suppression of macrophage inflammatory responses by PPARs. Proc Natl Acad Sci U S A 2003; 100(11): 6295-6296.
34. Rosen ED, Spiegelman BM. PPARgamma : a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem 2001; 276(41): 37731-37734.
35. Ren D, Collingwood TN, Rebar EJ, Wolffe AP, Camp HS. PPARgamma knockdown by engineered transcription factors: exogenous PPARgamma2 but not PPARgamma1 reactivates adipogenesis. Genes Dev 2002; 16(1): 27-32.
36. Nagashima K, Lopez C, Donovan D, et al. Effects of the PPARgamma agonist pioglitazone on lipoprotein metabolism in patients with type 2 diabetes mellitus. J Clin Invest 2005; 115(5): 1323-1332.
37. Sakamoto J, Kimura H, Moriyama S, et al. Activation of human peroxisome proliferator-activated receptor (PPAR) subtypes by pioglitazone. Biochem Biophys Res Commun 2000; 278(3): 704-711.
38. Rhee EJ, Oh KW, Lee WY, et al. Effects of two common polymorphisms of peroxisome proliferator-activated receptor-gamma gene on metabolic syndrome. Arch Med Res 2006; 37(1): 86-94.
39. Hoeks J, Hesselink MK, Russell AP, et al. Peroxisome proliferator-activated receptor-gamma coactivator-1 and insulin resistance: acute effect of fatty acids. Diabetologia 2006; 49(10): 2419-2426.
40. Fang CX, Dong F, Nunn JM, Ren J. Metallothionein transgene prevents insulin resistance-induced cardiac contractile dysfunction by promoting mitochondrial biogenesis through upregulation of peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) alpha. Circulation 2006: 114(18): II-843.
41. Fang CX, Dong F, Ren BH, Epstein PN, Ren J. Metallothionein alleviates cardiac contractile dysfunction induced by insulin resistance: role of Akt phosphorylation, PTB1B, PPARgamma and c-Jun. Diabetologia 2005; 48(11): 2412-2421.
42. Gerstein HC, Yusuf S, Bosch J, et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomized controlled trial. Lancet 2006; 368(9541): 1096-1105.
43. Arany Z, Novikov M, Chin S, Ma Y, Rosenzweig A, Spiegelman BM. Transverse aortic constriction leads to accelerated heart failure in mice lacking PPAR-gamma coactivator 1alpha. Proc Natl Acad Sci U S A 2006; 103(26): 10086-10091.
44. Patsouris D, Mandard S, Voshol PJ, et al. PPARalpha governs glycerol metabolism. J Clin Invest 2004; 114(1): 94-103.
45. Tenenbaum H, Behar S, Boyko V, et al. Long-term effect of bezafibrate on pancreatic beta-cell function and insulin resistance in patients with diabetes. Atherosclerosis 2006 [Epub Ahead of Print].
46. Gilde AJ, van der Lee KA, Willemsen PH, et al. Peroxisome proliferator-activated receptor (PPAR) alpha and PPARbeta/delta, but not PPARgamma, modulate the expression of genes involved in cardiac lipid metabolism. Circ Res 2003; 92(5): 518-524.
47. Tanaka T, Yamamoto J, Iwasaki S, et al. Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic syndrome. Proc Natl Acad Sci U S A 2003; 100(26): 15924-15929.
48. Barish GD, Narkar VA, Evans RM. PPAR delta: a dagger in the heart of the metabolic syndrome. J Clin Invest 2006; 116(3): 590-597.
49. Armoni M, Kritz N, Harel C, et al. Peroxisome proliferator-activated receptor-gamma represses GLUT4 promoter activity in primary adipocytes, and rosiglitazone alleviates this effect. J Biol Chem 2003; 278(33): 30614-30623.
50. Berthiaume M, Sell H, Lalonde J, et al. Actions of PPARgamma agonism on adipose tissue remodeling, insulin sensitivity, and lipemia in absence of glucocorticoids. Am J Physiol Regul Integr Comp Physiol 2004; 287(5): R1116-R1123.
51. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev 2005; 26(3):439-451.
52. Pajvani UB, Hawkins M, Combs TP, et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem 2004; 279(13): 12152-12162.
53. Armoni M, Harel C, Bar-Yoseph F, Milo S, Karnieli E. Free fatty acids repress the GLUT4 gene expression in cardiac muscle via novel response elements. J Biol Chem 2005; 280(41): 34786-34795.
54. LeBrasseur NK, Kelly M, Tsao TS, et al. Thiazolidinediones can rapidly activate AMP-activated protein kinase in mammalian tissues. Am J Physiol Endocrinol Metab 2006; 291(1): E175-E181.
55. Li X, Hansen PA, Xi L, Chandraratna RA, Burant CF. Distinct mechanisms of glucose lowering by specific agonists for peroxisomal proliferator activated receptor gamma and retinoic acid X receptors. J Biol Chem 2005; 280(46): 38317-38327.
56. Benndorf RA, Rudolph T, Appel D, et al. Telmisartan improves insulin sensitivity in nondiabetic patients with essential hypertension. Metabolism 2006; 55(9): 1159-1164.
57. Nesto RW, Bell D, Bonow RO, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. October 7, 2003. Circulation 2003; 108(23): 2941-2948.
58. Sotiropoulos KB, Clermont A, Yasuda Y, et al. Adipose-specific effect of rosiglitazone on vascular permeability and protein kinase C activation: novel mechanism for PPARgamma agonist's effects on edema and weight gain. FASEB J 2006; 20(8): 1203-1205.
59. Dragomir E, Tircol M, Manduteanu I, Voinea M, Simionescu M. Aspirin and PPAR-alpha activators inhibit monocyte chemoattractant protain-1 expression induced by high glucose concentration in human endothelial cells. Vascul Pharmacol 2006; 44(6): 440-449.
60. Goikoetxea MJ, Beaumont J, Diez J. Peroxisome proliferator-activated receptor alpha and hypertensive heart disease. Drugs 2004; 64 Suppl, 2:9-18.
61. Israelian-Konaraki Z, Reaven PD. Peroxisome proliferator-activated receptor-alpha and atherosclerosis: from basic mechanisms to clinical implications. Cardiology 2005; 103(1):1-9.
62. Kleemann R, Gervois PP, Verschuren L, Staels B, Princen HM, Kooistra T. Fibrates down-regulate IL-1-stimulated C-reactive protein gene expression in hepatocytes by reducing nuclear p50-NFkappa B-C/EBP-beta complex formation. Blood 2003; 101(2): 545-551.
63. Ding G, Cheng L, Qin Q, Frontin S, Yang Q. PPARdelta modulates lipopolysaccharide-induced TNFalpha inflammation signaling in cultured cardiomyocytes. J Mol Cell Cardiol 2006; 40(6): 821-828.
64. Calabro P, Samudio I, Safe SH, Willerson JT, Yeh ET. Inhibition of tumor-necrosis-factor-alpha induced endothelial cell activation by a new class of PPAR-gamma agonists. An in vitro study showing receptor-independent effects. J Vasc Res 2005; 42(6): 509-516.
65. Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macro Vascular Events): a randomised controlled trial. Lancet 2005; 366(9493): 1279-1289.
66. Jiang C, Ting AT, Seed B. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 1998; 391(6662): 82-86.
67. Rios-Vazquez R, Marzoa-Rivas R, Gil-Ortega I, Kaski JC. Peroxisome Proliferator-Activated Receptor-gamma Agonists for Management and Prevention of Vascular Disease in Patients with and without Diabetes Mellitus. Am J Cardiovasc Drugs 2006; 6(4): 231-242.
68. Pourcet B, Fruchart JC, Staels B, Glineur C. Selective PPAR modulators, dual and pan PPAR agonists: multimodal drugs for the treatment of Type 2 diabetes and atherosclerosis. Expert Opin Emerg Drugs 2006; 11(3): 379-401.
69. Fievet C, Fruchart JC, Staels B. PPARalpha and PPARgamma dual agonists for the treatment of type 2 diabetes and the metabolic syndrome. Curr Opin Pharmacol 2006 [Epub Ahead of Print].
70. Xu Y, Etgen GJ, Broderick CL, et al. Design and Synthesis of Dual Peroxisome Proliferator-Activated Receptors gamma and delta Agonists as Novel Euglycemic Agents with a Reduced Weight Gain Profile. J Med Chem 2006; 49(19): 5649-5652.
71. Gizard F, Amant C, Barbier O, et al. PPAR alpha inhibits vascular smooth muscle cell proliferation underlying intimal hyperplasia by inducing the tumor suppressor p16INK4a. J Clin Invest 2005; 115(11): 3228-3238.
72. Ringseis R, Muller A, Herter C, Gahler S, Steinhart H, Eder K. CLA isomers inhibit TNFalpha-induced eicosanoid release from human vascular smooth muscle cells via a PPARgamma ligand-like action. Biochim Biophys Acta 2006; 1760(2): 290-300.
73. Xiong C, Mou Y, Zhang J, et al. Impaired expression of PPAR gamma protein contributes to the exaggerated growth of vascular smooth muscle cells in spontaneously hypertensive rats. Life Sci 2005; 77(24): 3037-3048.
74. Gervois P, Vu-Dac N, Kleemam R, et al. Negative regulation of human fibrinogen gene expression by peroxisome proliferator-activated receptor alpha agonists via inhibition of CCAAT box/enhancer-binding protein beta. J Biol Chem 2001; 276(36): 33471-33477.
75. Kon KK, Yeal AJ, Hwan HS, et al. Effects of fenofibrate on lipoproteins, vasomotor function, and serological markers of inflammation, plaque stabilization, and hemostasis. Atherosclerosis 2004; 174(2): 379-383.
76. Blaschke F, Spanheimer R, Khan M, Law RE. Vascular effects of TZDs: new implications. Vascul Pharmacol 2006; 45(1): 3-18.
77. Goya K, Sumitani S, Xu X, et al. Peroxisome proliferator-activated receptor alpha agonists increase nitric oxide synthase expression in vascular endothelial cells. Arterioscler Thromb Vasc Biol 2004; 24(4): 658-663.
78. Russell AP, Feilchenfeldt J, Schreiber S, et al. Endurance training in humans leads to fiber type-specific increases in levels of peroxisome proliferator-activated receptor-gamma coactivator-1 and peroxisome proliferator-activated receptor-alpha in skeletal muscle. Diabetes 2003; 52(12): 2874-2881.
79. Takahashi S, Tanaka T, Kodama T, Sakai J. Peroxisome proliferator-activated receptor delta (PPARdelta), a novel target site for drug discovery in metabolic syndrome. Pharmacol Res 2006; 53(6): 501-507.
80. Barlocco D. Muraglitazar (Bristol-Myers Squibb/Merck). Curr Opin Investig Drugs 2005; 6(4): 427-434.
81. Fagerberg B, Edwards S, Halmos T, et al. Tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma agonist, dose-dependently improves the metabolic abnormalities associated with insulin resistance in a non-diabetic population. Diabetologia, 2005; 48(9): 1716-1725.
82. Harrity T, Farrelly D, Tieman A, et al. Muraglitazar, a novel dual (alpha/gamma) peroxisome proliferator-activated receptor activator, improves diabetes and other metabolic abnormalities and preserves beta-cell function in db/db mice. Diabetes 2006; 55(1): 240-248.