Peroxisome proliferator-activated receptor β/δ as a therapeutic target for matabolic diseases

Expert Opinion on Therapeutic Targets

Volumn 9, Issue 4, 2005, Pages 861-873

  Bedu, Elodie ^a   Wahli, Walter ^a   Desvergne, Béatrice ^a  

^a UNIVERSITY OF LAUSANNE   (Switzerland)

Author keywords

Atherogenic lipoprotein profile; Fatty acid oxidation; Heart; Muscle; Obesity; Peroxisome proliferator activated receptor (PPAR)

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; 3 [3 [[2 CHLORO 3 (TRIFLUOROMETHYL)BENZYL](2 DIPHENYLETHYL)AMINO]PROPOXY]PHENYLACETIC ACID; 4 [4 [3 (4 ACETYL 3 HYDROXY 2 PROPYLPHENOXY)PROPOXY]PHENOXY]ACETIC ACID; [2 METHYL 4 [4 METHYL 2 (4 TRIFLUOROMETHYLPHENYL) 5 THIAZOLYLMETHYLTHIO]PHENOXY]ACETIC ACID; FATTY ACID DERIVATIVE; FIBRIC ACID DERIVATIVE; GW 0742; HORMONE RECEPTOR; HORMONE RECEPTOR AFFECTING AGENT; ISOPROTEIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; RETINOIC ACID; UNCLASSIFIED DRUG;

ADIPOSE TISSUE; CARCINOGENESIS; CHOLESTEROL METABOLISM; DISEASE PREDISPOSITION; DRUG MECHANISM; DRUG PENETRATION; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG STRUCTURE; DRUG TARGETING; ENERGY METABOLISM; FATTY ACID OXIDATION; GASTROINTESTINAL TUMOR; GENE OVEREXPRESSION; GENETIC TRANSCRIPTION; HEART MUSCLE METABOLISM; HUMAN; INSULIN SENSITIVITY; LIPID BLOOD LEVEL; LIPID STORAGE; LIPOLYSIS; METABOLIC DISORDER; METABOLIC SYNDROME X; MOUSE; MUSCLE METABOLISM; NONHUMAN; OBESITY; PROTEIN ANALYSIS; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN INDUCTION; REVIEW; SKELETAL MUSCLE; TISSUE REPAIR; TISSUE SPECIFICITY;

ANIMALS; GENE EXPRESSION REGULATION; HUMANS; METABOLIC DISEASES; PPAR DELTA; PPAR-BETA;

EID: 23644445667     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728222.9.4.861     Document Type: Review

References (85)

1. KOPELMAN PG: Obesity as a medical problem. Nature (2000) 404(6778):635-643.
2. DREYER C KG, KELLER H, GIVEL F, HELFTENBEIN G, WAHLI W: Control of the peroxisomal β-oxidation pathway by a novel family of nuclear hormone receptors. Cell (1992) 68:879-887.
3. ISSEMANN I, GREEN S: Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature (1990) 347(6294):645-650.
4. DESVERGNE B, WAHLI W: Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr. Rev. (1999) 20(5):649-688.
5. FEIGE JN, GELMAN L, TUDOR C et al.: Fluorescence imaging reveals the nuclear behavior of PPAR/RXR heterodimers in the absence and presence of ligand. J. Biol. Chem. (2005) 280(18):17880-17890.
6. CHAWLA A, REPA JJ, EVANS RM, MANGELSDORF DJ: Nuclear receptors and lipid physiology: Opening the X-files. Science (2001) 294(5548):1866-1870.
7. LOCK EA, MITCHELL AM, ELCOMBE CR: Biochemical mechanisms of induction of hepatic peroxisome proliferation. Ann. Rev. Pharmacol Toxicol. (1989) 29:145-163.
8. DESVERGNE B, MICHALIK L, WAHLI W: Be fit or be sick: peroxisome proliferator-activared receptors are down the road. Mol. Endocrinol. (2004) 18(6):1321-1332.
9. SHAW N, ELHOLM M, NOY N: Retinoic acid is a high affinity selective ligand for the peroxisome proliferator-activated receptor beta/delta. J. Biol. Chem. (2003) 278(43):41589-41592.
10. PETERS JM, LEE SST, LI W et al.: Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta (delta). Mol. Cell. Biol. (2000) 20(14):5119-5128.
11. BARAK Y, LIAO D, HE W et al.: Effects of peroxisome proliferator-activated receptor delta on placentation, adiposity, and colorectal cancer. Proc. Natl. Acad. Sci. USA (2002) 99(1):303-308.
12. MICHALIK L, DESVERGNE B, TAN NS et al.: Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)alpha and PPARbeta mutant mice. J. Cell. Biol. (2001) 154(4):799-814.
13. SCHMIDT AEN, RUTLEDGE SJ, VOGEL R, SHINAR D, RODAN GA: Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol. Endocrinol. (1992) 6:1634-1641.
14. AMRI E-Z, BONINO F, AILHAUD G, ABUMRAD NA, GRIMALDI PA: Cloning of a protein that mediates transcriptional effects of fatty acids in preadipocytes. J. Biol. Chem. (1995) 270(5):2367-2371.
15. KLIEWER S, FORMAN B, BLUMBERG B et al.: Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc. Natl. Acad. Sci. USA (1994) 91(15):7355-7359.
16. KROGSDAM AM NC, NEVE S, HOLST D et al.: Nuclear receptor corepressor-dependent repression of peroxisome-proliferator-activated receptor delta-mediated transactivation. Biochem. J. (2002) 363:157-165.
17. XU HE LM, MONTANA VG, PARKS DJ et al: Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol. Cell. (1999) 3:397-403.
18. VAN VELDHOVEN PP, MANNAERTS GP, DECLERCQ P, BAES M: Do sphingoid bases interact with the peroxisome proliferator activated receptor [alpha] (PPAR-[alpha])? Cell. Signal. (2000) 12(7):475-479.
19. FORMAN BM, CHEN J, EVANS RM: Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc. Natl. Acad. Sci. USA (1997) 94(9):4312-4317.
20. WANG D, WANG H, SHI Q et al.: Prostaglandin E2 promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor [delta]. Cancer Cell (2004) 6(3):285-295.
21. LIM H, DEY SK: Minireview: A Novel Pathway of Prostacyclin Signaling-Hanging Out with Nuclear Receptors. Endocrinology (2002) 143(9):3207-3210.
22. MCKENNA NJ, O'MALLEY BW: Minireview: Nuclear Receptor Coactivators-An Update. Endocrinology (2002) 143(7):2461-2465.
23. ROBYR D, WOLFFE AP, WAHLI W: Nuclear hormone receptor coregulators in action: Diversity for shared tasks. Mol. Endocrinol. (2000) 14(3):329-347.
24. SURAPUREDDI S, YU S, BU H et al.: Identification of a transcriptionally active peroxisome proliferator-activated receptor alpha-interacting cofactor complex in rat liver and characterization of PRIC285 as a coactivaior. Proc. Natl. Acad. Sci. USA (2002) 99(18):11836-11841.
25. SHI Y, HON M, EVANS RM: The peroxisome proliferator-activated receptor delta, an integrator of transcriptional repression and nuclear receptor signaling. Proc. Natl. Acad. Sci. USA (2002) 99(5):2613-2618.
26. DELFRIVE P, DE BOSSCHER K, BESNARD S et al.: Peroxisome Proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappa B and AP-1. J. Biol. Chem. (1999) 274(45):32048-32054.
27. GLASS CK, ROSENFELD MG: The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev. (2000) 14(2):121-141.
28. BRAISSANT O, WAHLI W: Differential expression of peroxisome proliferator-activated receptor-alpha, -beta, and -gamma during rat embryonic development. Endocrinology (1998) 139(6):2748-2754.
29. ESCHER P, BRAISSANT O, BASU-MODAK S et al.: Rat PPARs: Quantitative analysis in adult rat tissues and regulation in fasting and refeeding. Endocrinology (2001) 142(10):4195-4202.
30. AMRI EZ, BONINO F, AILHAUD G, ABUMRAD NA, GRIMALDI PA: Cloning of a protein that mediates transcriptional effects of fatty acids in preadipocytes. J. Biol. Chem. (1995) 270(5):2367-2371.
31. BASTIE C, HOLST D, GAILLARD D, JEHL-PIETRI C, GRIMALDI PA: Expression of peroxisome proliferator-activated receptor PPARdelta promotes induction of PPARgamma and adipocyte differentiation in 3T3C2 fibroblasts. J. Biol. Chem. (1999) 274(31):21920-21925.
32. HOLST D, LUQUET S, KRISTIANSEN K, GRIMALDI PA: Roles of peroxisome proliferator-activated receptors delta and gamma in myoblast transdifferentiation. Exp. Cell. Res. (2003) 288(1):168-176.
33. MATSUSUE K, PETERS JM, GONZALEZ FJ: PPARbeta/delta potentiates PPARgamma-stimulated adipocyte differentiation. FASEB J. (2004) 18(12):1477-1479.
34. GONZALEZ F: Getting fat: Two new players in molecular adipogenesis. Cell Metabolism (2005) 1:85-86.
35. TONTONOZ P, HU E, SPIEGELMAN BM: Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell (1994) 79(7):1147-1156.
36. WANG YX, LEE CH, TIEP S et al.: Peroxisome proliferator-activated receptor [delta] activates fat metabolism to prevent obesity. Cell (2003) 113(2):159-170.
37. 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. USA (2003) 100(26):15924-15929.
38. JEUKENDRUP AE: Regulation of fat metabolism in skeletal muscle. Proc. Natl. Acad. Sci. USA (2002) 967(1):217-235.
39. MUOIO DM, MACLEAN PS, LANG DB et al.: Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of peroxisome proliferator-activated receptor (PPAR) alpha knock-out mice. Evidence for compensatory regulation by PPAR delta. J. Biol. Chem. (2002) 277:26089-26097.
40. CHEVILLOTTE E, RIEUSSET J, ROQUES M, DESAGE M, VIDAL H: The regulation of uncoupling protein-2 gene expression by omega -6 polyunsaturated fatty acids in human skeletal muscle cells involves multiple pathways, including the nuclear receptor peroxisome proliferator-activated receptor beta. J. Biol. Chem. (2001) 276(14):10853-10860.
41. HOLST D, LUQUET S, NOGUEIRA V et al.: Nutritional regulation and role of peroxisome proliferator-activated receptor [delta] in fatty acid catabolism in skeletal muscle. Biochim. Biophys. Act. (2003) 1633(1):43-50.
42. DRESSEL U, ALLEN TL, PIPPAL JB et al.: The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells. Mol. Endocrinol. (2003) 17(12):2477-2493.
43. LUQUET S, LOPEZ-SORIANO J, HOLST D et al.: Peroxisome proliferator-activated receptor delta; controls muscle development and oxidative capability. FASEB J. (2003) 17(15):2299-301.
44. WANG YX, ZHANG CL, YU RT et al.: Regulation of muscle fiber type and running endurance by PPARdelta. PLoS Biology (2004) 2(10):e294.
45. HOROWITZ JF, LEONE TC, FENG W, KELLY DP, KLEIN S: Effect of endurance training on lipid metabolism in women: a potential role for PPARalpha in the metabolic response to training. Am. J. Physiol. Endocrinol. Metab. (2000) 279(2):E348-E355.
46. PUIGSERVER P, SPIEGELMAN BM: Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1 alpha): Transcriptional coactivator and metabolic regulator. Endocr. Rev. (2003) 24(1):78-90.
47. 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.
48. BARGER PM, BROWNING AC, GARNER AN, KELLY DP: p38 mitogen-activated protein kinase activates peroxisome proliferator-activated receptor alpha. A potential role in the cardiac metabolic stress response. J. Biol. Chem. (2001) 276(48):44495-44501.
49. GILDE AJ, VAN DER LEE KAJM, WILLEMSEN PHM 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.
50. 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. (2004) 10(11):1245-1250.
51. CHENG L, DING G, QIN Q et al.: Peroxisome proliferator-activated receptor [delta] activates fatty acid oxidation in cultured neonatal and adult cardiomyocytes. Biochem. Biophys. Res. Commun. (2004) 313(2):277-286.
52. DELUCA JG, DOEBBER TW, KELLY LJ et al.: Evidence for peroxisome proliferator-activated receptor (PPAR)alpha -independent peroxisome proliferation: effects of PPARgamma/delta -Specific agonists in PPARalpha null Mice. Mol. Pharmacol. (2000) 58(3):470-476.
53. WATANABE K, FUJII H, TAKAHASHI T et al.: Constitutive regulation of cardiac fatty acid metabolism through peroxisome proliferator-activated receptor alpha associated with age-dependent cardiac toxicity. J. Biol. Chem. (2000) 275(29):22293-22299.
54. YOUNG ME, LAWS FA, GOODWIN GW, TAEGTMEYER H: Reactivation of peroxisome proliferator-activated receptor alpha is associated with contractile dysfunction in hypertrophied rat heart. J. Biol. Chem. (2001) 276(48):44390-44395.
55. LEHMAN JJ, KELLY DP: Gene regulatory mechanisms governing energy metabolism during cardiac hypertrophic growth. Heart Fail. Rev. (2002) 7(2):175-185.
56. SKOGSBERG J, MCMAHON AD, KARPE F et al.: Peroxisome proliferator activated receptor delta genotype in relation to cardiovascular risk factors and risk of coronary heart disease in hypercholesterolaemic men. J. Intern. Med. (2003) 254(6):597-604.
57. 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. USA (2001) 98(9):5306-5311.
58. WALLACE JM, SCHWARZ M, COWARD P et al.: Effects of peroxisome proliferator-activated receptor alpha/delta agonists on HDL-cholesterol in vervet monkeys. J. Lipid Res. (2005):M500002-JLR500200.
59. AKIYAMA TE, LAMBERT G, NICOL CJ et al.: Peroxisome proliferator-activated receptor beta/delta regulates very low density lipoprotein production and catabolism in mice on a western diet. J. Biol. Chem. (2004) 279(20):20874-20881.
60. LEIBOWITZ MD, FIEVET C, HENNUYER N et al.: Activation of PPAR[delta] alters lipid metabolism in db/db mice. FEBS Lett. (2000) 473(3):333-336.
61. TAN NS, MICHALIK L, DESVERGNE B, WAHLI W: Peroxisome proliferator-activated receptor-beta as a target for wound healing drugs. Expert Opin. Ther. Targets (2004) 8(1):39-48.
62. CASTRILLO A, TONTONOZ P: Nuclear receptors in macrophage biology: At the Crossroads of Lipid Metabolism and Inflammation. Ann. Rev. Cell. Dev. Biol. (2004) 20(1):455-480.
63. TONTONOZ P NL, ALVAREZ JG, THOMAZY VA, EVANS RM: PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell (1998) 93(2):241-252.
64. LEE CH, CHAWLA A, URBIZTONDO N et al.: Transcriptional repression of atherogenic inflammation: Modulation by PPARdelta. Science (2003) 302(5644):453-457.
65. CHAWLA A, LEE C-H, BARAK Y et al.: PPARdelta is a very low-density lipoprotein sensor in macrophages. Proc. Natl. Acad. Sci. USA (2003) 100(3):1268-1273.
66. TARGETT-ADAMS P, MCELWEE MJ, EHRENBORG E, GUSTAFSSON MC, PALMER CN, McLAUCHLAN J: A PPAR response element regulates transcription of the gene for human adipose differentiation-related protein. Biochim. Biophys. Act. (2005) 1728(1-2):95-104.
67. VOSPER H, PATEL L, GRAHAM TL et al.: The peroxisome proliferator-activated receptor delta promotes lipid accumulation in human macrophages. J. Biol. Chem. (2001) 276(47):44258-44265.
68. GUAN Y: Peroxisome proliferator-activated receptor family and its relationship to renal complications of the metabolic syndrome. J. Am. Soc. Nephrol. (2004) 15(11):2801-2815.
69. TANNER CJ, BARAKAT HA, DOHM GL et al.: Muscle fiber type is associated with obesity and weight loss. Am. J. Physiol. Endocrinol. Metab. (2002) 282(6):E1191-E1196.
70. PATTI ME, BUTTE AJ, CRUNKHORN S et al.: Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc. Natl. Acad. Sci. USA (2003) 100(14):8466-8471.
71. KRAMER DK, AL-KHALILI L, PERRINI S et al.: Direct activation of glucose transport in primary human myotubes after activation of peroxisome proliferator-activated receptor delta. Diabetes (2005) 54(4):1157-1163.
72. FRANCIS GA, ANNICOTTE J-S, AUWERX J: PPAR agonists in the treatment of atherosclerosis. Curr. Opin. Pharmacol. (2003) 3(2):186-191.
73. MICHALIK L DB, WAHLI W: Peroxisome-proliferator-activated receptors and cancers: complex stories. Nat. Rev. Cancer. (2004) 4(1):61-70.
74. MÜLLER R: Crosstalk of oncogenic and prostanoid signaling pathways. J. Cancer Res. Clin. Oncol. (2004) 130(8):429-444.
75. PARK BH, VOGELSTEIN B, KINZLER KW: Genetic disruption of PPARdelta decreases the tumorigenicity of human colon cancer cells. Proc. Natl. Acad. Sci. USA (2001) 98(5):2598-2603.
76. SHAO J, SHENG H, DUBOIS RN: Peroxisome proliferator-activated receptors modulate K-ras-mediated transformation of intestinal epithelial cells. Cancer Res. (2002) 62(11):3282-3288.
77. GUPTA RA, WANG D, KATKURI S et al.: Activation of nuclear hormone receptor peroxisome proliferator-activated receptor-[delta] accelerates intestinal adenoma growth. Nat. Med. (2004) 10(3):245-247.
78. DI-POI N, TAN NS, MICHALIK L, WAHLI W, DESVERGNE B: Antiapoptotic role of PPAR[beta] in keratinocytes via transcriptional control of the Akt1 signaling pathway. Mol. Cell (2002) 10(4):721-733.
79. HARMAN FS, NICOL CJ, MARIN HE et al.: Peroxisome proliferator-activated receptor-[delta] attenuates colon carcinogenesis. Nat. Med. (2004) 10(5):481-483.
80. REED KR, SANSOM OJ, HAYES AJ et al.: PPARdelta status and Apc-mediated tumourigenesis in the mouse intestine. Oncogene (2004) 23:8992-8996.
81. KIM DJ, AKIYAMA TE, HARMAN FS et al.: Peroxisome proliferator-activated receptor beta (delta)-dependent regulation of ubiquitin C expression contributes to attenuation of skin carcinogenesis. J. Biol. Chem. (2004) 279(22):23719-23727.
82. LOHRAY BB, LOHRAY VB, BAJJI AC et al.: (-)3-[4-[2-(Phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid [(-)DRF 2725]: a dual PPAR agonist with potent antihyperglycemic and lipid modulating activity. J. Med. Chem. (2001) 44(16):2675-2678.
83. MIAO B, ZONDLO S, GIBBS S et al.: Raising HDL cholesterol without inducing hepatic steatosis and hypertriglyceridemia by a selective LXR modulator. J. Lipid Res. (2004) 45(8):1410-1417.
84. SZNAIDMAN ML, HAFFNER CD, MALONEY PR et al.: Novel selective small molecule agonists for peroxisome proliferator-activated receptor [delta] (PPAR[delta])-synthesis and biological activity. Bioorg. Med. Chem. Lett. (2003) 13(9):1517-1521.
85. BERGER J, LEIBOWITZ MD, DOEBBER TW et al.: Novel Peroxisome Proliferator-activated Receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. J. Biol. Chem. (1999) 274(10):6718-6725.