Receptor nomenclature NR1C1
Receptor code 4.10.1:FA:1:C1
Molecular information Hs: 468aa, Q07869, chr. 22q13.311
Rn: 468aa, P37230, chr. 7q342
Mm: 468aa, P23204, chr. 15 E23
DNA binding
   Structure Heterodimer, RXR partner
   HRE core sequence AACTAGGNCA A AGGTCA (DR-1, DR-2)
Partners RXR (physical, functional) DNA binding4
Agonists GW409544 (8.7), LY-518674 (7.6), LY-510929 (7.55), TZD18 (7.55), LTB4 (7), oleylethanolamide (6.92), LY-465608 (6.8), pirinixic acid (6.22), fatty acids (6), ragaglitazar (6), AD-5061 (5.55), fenofibric acid (4.46) [pIC50]522; GW7647 (8.22), GW9578 (7.3), TAK-559 (7.17), KRP-297/MK-0767 (6.8), eicosatetraenoic acid (6.7), farglitazar (6.35), reglitazar (5.72), DRF 2519 (∼5), pristanic acid (4.4), bezafibrate (4.3), clofibrate (4.25) [pEC50]6,13,14,18,2333; KRP-297/MK-0767 (7.64), 8S-HETE (7), GW2331 (6.8), NS-220* (6.73), [3H]AD-5061* (5.5) [pKd]9,17,18,3438; pterostilbene, tetradecylglycidic acid, ortylthiopropionic acid39,40
Antagonists MK886 (4.6) [pIC50]41
Corepressors NRIP1, NCOR139,5357
Biologically important isoforms PPARα {Hs, Mm, Rn}: encoded by eight exons13, 58; PPARαtr (truncated) {Hs}: lacks exon 6, truncated protein lacking part of hinge region and LBD, dominant-negative, 20–50% of total PPARα mRNA, not detected in rodents59
Tissue distribution Very active peroxisomal β-oxidation tissues; liver, brown fat, kidney, heart, skeletal muscle, large intestine {Hs, Mm, Rn} [Northern blot, Q-PCR, in situ hybridization, immunohistology]39
Main target genes Activated: liver fatty acid binding protein39,60, Acyl-CoA oxidase {Rn}61,62, bifunctional enzyme {Rn}61, CPTI {Hs}6365, MCAD {Rn}66, FIAF {Mm}67, FATP {Mm}68, apolipoprotein A-II {Mm}69, G0/G1 switch gene 2 (G0S2) {Mm}70
Mutant phenotype Hypothermia and hypoglycemia upon fasting, reduced insulin resistance, prolonged inflammatory reaction, transient delay in skin healing, resistance to fibrate-induced cancer {Mm} [knockout]7,7176; overexpression in the heart leads to cardiac insulin resistance associated with defects in insulin signaling and STAT3 activity, reduced heart function {Mm} [transgenesis]77,78; overexpression in muscle leads to the development of glucose intolerance, increased fatty acid oxidation rates, reduced AMP-activated protein kinase activity, reduced insulin-stimulated glucose uptake, repression of GLUT4 gene {Mm} [transgenesis]79; PPARαΔ13: dominant-negative mutant results in transient-impaired wound-healing and impaired inflammatory phase {Mm} [transgenesis]80
Human disease Arteriosclerosis81,82
  • aa, amino acids; chr., chromosome; HRE, hormone response element; HETE, hydroxyeicosatetraenoic acid; Q-PCR, quantitative polymerase chain reaction; FIAF, fasting-induced adipose factor; BFE, bifunctional enzyme; CREBBP, cAMP response element binding protein binding protein; CPTI, carnitine palmitoyl transferase; MCAD, medium-chain acyl-CoA dehydrogenase; FATP, fatty acid transport protein

  • * Radioligand

  • 1. Sher T, Yi HF, McBride OW, and Gonzalez FJ (1993) cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry 32: 5598-5604

  • 2. Gottlicher M, Widmark E, Li Q, and Gustafsson JA (1992) Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. Proc Natl Acad Sci USA 89: 4653-4657

  • 3. Issemann I and Green S (1990) Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature (Lond) 347: 645-650

  • 4. Kliewer SA, Umesono K, Noonan DJ, Heyman RA, and Evans RM (1992) Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature (Lond) 358: 771-774

  • 5. Brooks DA, Etgen GJ, Rito CJ, Shuker AJ, Dominianni SJ, Warshawsky AM, Ardecky R, Paterniti JR, Tyhonas J, Karanewsky DS, et al. (2001) Design and synthesis of 2-methyl-2-[4-(2-[5-methyl-2-aryloxazol-4-yl]ethoxy)phenoxy]propionic acids: a new class of dual PPARalpha/gamma agonists. J Med Chem 44: 2061-2064

  • 6. Brown PJ, Stuart LW, Hurley KP, Lewis MC, Winegar DA, Wilson JG, Wilkison WO, Ittoop OR, and Willson TM (2001) Identification of a subtype selective human PPARalpha agonist through parallel-array synthesis. Bioorg Med Chem Lett 11: 1225-1227

  • 7. Devchand PR, Keller H, Peters JM, Vazquez M, Gonzalez FJ, and Wahli W (1996) The PPARalpha-leukotriene B4 pathway to inflammation control. Nature (Lond) 384: 39-43

  • 8. Ebdrup S, Pettersson I, Rasmussen HB, Deussen HJ, Frost Jensen A, Mortensen SB, Fleckner J, Pridal L, Nygaard L, and Sauerberg P (2003) Synthesis and biological and structural characterization of the dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist ragaglitazar. J Med Chem 46: 1306-1317

  • 9. Forman BM, Chen J, and Evans RM (1997) Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci USA 94: 4312-4317

  • 10. Fu J, Gaetani S, Oveisi F, Lo Verme J, Serrano A, Rodriguez De Fonseca F, Rosengarth A, Luecke H, Di Giacomo B, et al. (2003) Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature (Lond) 42: 90-93

  • 11. Fu J, Oveisi F, Gaetani S, Lin E, and Piomelli D (2005) Oleoylethanolamide, an endogenous PPAR-alpha agonist, lowers body weight and hyperlipidemia in obese rats. Neuropharmacology 48: 1147-1153

  • 12. Guo Q, Sahoo SP, Wang PR, Milot DP, Ippolito MC, Wu MS, Baffic J, Biswas C, Hernandez M, Lam MH, et al. (2004) A novel peroxisome proliferator-activated receptor alpha/gamma dual agonist demonstrates favorable effects on lipid homeostasis. Endocrinology 145: 1640-1648

  • 13. Henke BR (2004) Peroxisome proliferator-activated receptor alpha/gamma dual agonists for the treatment of type 2 diabetes. J Med Chem 47: 4118-4127

  • 14. Inoue I, Itoh F, Aoyagi S, Tazawa S, Kusama H, Akahane M, Mastunaga T, Hayashi K, Awata T, Komoda T, et al. (2002) Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. Biochem Biophys Res Commun 290: 131-139

  • 15. Krey G, Braissant O, L'Horset F, Kalkhoven E, Perroud M, Parker MG, and Wahli W (1997) Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Mol Endocrinol 11: 779-791

  • 16. Liu K, Xu L, Berger JP, Macnaul KL, Zhou G, Doebber TW, Forrest MJ, Moller DE, and Jones AB (2005) Discovery of a novel series of peroxisome proliferator-activated receptor alpha/gamma dual agonists for the treatment of type 2 diabetes and dyslipidemia. J Med Chem 48: 2262-2265

  • 17. Sakamoto J, Kimura H, Moriyama S, Odaka H, Momose Y, Sugiyama Y, and Sawada H (2000) Activation of human peroxisome proliferator-activated receptor (PPAR) subtypes by pioglitazone. Biochem Biophys Res Commun 278: 704-711. subtypes by pioglitazone. Biochem Biophys Res Commun 278:704–711

  • 18. Sakamoto J, Kimura H, Moriyama S, Imoto H, Momose Y, Odaka H, and Sawada H (2004) A novel oxyiminoalkanoic acid derivative, TAK-559, activates human peroxisome proliferator-activated receptor subtypes. Eur J Pharmacol 495: 17-26

  • 19. Xu HE, Lambert MH, Montana VG, Parks DJ, Blanchard SG, Brown PJ, Sternbach DD, Lehmann JM, Wisely GB, Willson TM, et al. (1999) Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell 3: 397-403

  • 20. Xu HE, Lambert MH, Montana VG, Plunket KD, Moore LB, Collins JL, Oplinger JA, Kliewer SA, Gampe RT Jr, McKee DD, et al. (2001) Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors. Proc Natl Acad Sci USA 98: 13919-13924

  • 21. Xu Y, Mayhugh D, Saeed A, Wang X, Thompson RC, Dominianni SJ, Kauffman RF, Singh J, Bean JS, Bensch WR, et al. (2003) Design and synthesis of a potent and selective triazolone-based peroxisome proliferator-activated receptor alpha agonist. J Med Chem 46: 5121-5124

  • 22. Xu Y, Rito CJ, Etgen GJ, Ardecky RJ, Bean JS, Bensch WR, Bosley JR, Broderick CL, Brooks DA, Dominianni SJ, et al. (2004) Design and synthesis of alpha-aryloxy-alpha-methylhydrocinnamic acids: a novel class of dual peroxisome proliferator-activated receptor alpha/gamma agonists. J Med Chem 47: 2422-2425

  • 23. Brown KK, Henke BR, Blanchard SG, Cobb JE, Mook R, Kaldor I, Kliewer SA, Lehmann JM, Lenhard JM, Harrington WW, et al. (1999) A novel N-aryl tyrosine activator of peroxisome proliferator-activated receptor-gamma reverses the diabetic phenotype of the Zucker diabetic fatty rat. Diabetes 48: 1415-1424

  • 24. Brown PJ, Winegar DA, Plunket KD, Moore LB, Lewis MC, Wilson JG, Sundseth SS, Koble CS, Wu Z, Chapman JM, et al. (1999) A ureido-thioisobutyric acid (GW9578) is a subtype-selective PPARalpha agonist with potent lipid-lowering activity. J Med Chem 42: 3785-3788

  • 25. Chakrabarti R, Misra P, Vikramadithyan RK, Premkumar M, Hiriyan J, Datla SR, Damarla RK, Suresh J, and Rajagopalan R (2004) Antidiabetic and hypolipidemic potential of DRF 2519–a dual activator of PPAR-alpha and PPAR-gamma. Eur J Pharmacol 491: 195-206

  • 26. Doebber TW, Kelly LJ, Zhou G, Meurer R, Biswas C, Li Y, Wu MS, Ippolito MC, Chao YS, Wang PR, et al. (2004) MK-0767, a novel dual PPARalpha/gamma agonist, displays robust antihyperglycemic and hypolipidemic activities. Biochem Biophys Res Commun 318: 323-328

  • 27. Henke BR, Blanchard SG, Brackeen MF, Brown KK, Cobb JE, Collins JL, Harrington WW Jr, Hashim MA, Hull-Ryde EA, Kaldor I, et al. (1998) N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 1. Discovery of a novel series of potent antihyperglycemic and antihyperlipidemic agents. J Med Chem 41: 5020-5036

  • 28. Heppner TJ, Bonev AD, Eckman DM, Gomez MF, Petkov GV, and Nelson MT (2005) Novel PPARgamma agonists GI 262570, GW 7845, GW 1929, and pioglitazone decrease calcium channel function and myogenic tone in rat mesenteric arteries. Pharmacology 73: 15-22

  • 29. Keller H, Dreyer C, Medin J, Mahfoudi A, Ozato K, and Wahli W (1993) Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers. Proc Natl Acad Sci USA 90: 2160-2164

  • 30. Keller H, Devchand PR, Perroud M, and Wahli W (1997) PPAR alpha structure-function relationships derived from species-specific differences in responsiveness to hypolipidemic agents. Biol Chem 378: 651-655

  • 31. Shibata T, Matsui K, Nagao K, Shinkai H, Yonemori F, and Wakitani K (1999) Pharmacological profiles of a novel oral antidiabetic agent, JTT-501, an isoxazolidinedione derivative. Eur J Pharmacol 364: 211-219

  • 32. Willson TM, Brown PJ, Sternbach DD, and Henke BR (2000) The PPARs: from orphan receptors to drug discovery. J Med Chem 43: 527-550

  • 33. Zomer AW, van Der Burg B, Jansen GA, Wanders RJ, Poll-The BT, and van Der Saag PT (2000) Pristanic acid and phytanic acid: naturally occurring ligands for the nuclear receptor peroxisome proliferator-activated receptor alpha. J Lipid Res 41: 1801-1807

  • 34. Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, Koble CS, Devchand P, Wahli W, Willson TM, Lenhard JM, et al. (1997) Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci USA 94: 4318-4323

  • 35. Kuwabara K, Murakami K, Todo M, Aoki T, Asaki T, Murai M, and Yano J (2004) A novel selective peroxisome proliferator-activated receptor alpha agonist, 2-methyl-c-5-[4-[5-methyl-2-(4-methylphenyl)-4-oxazolyl]butyl]-1,3-dioxan e-r-2-carboxylic acid (NS-220), potently decreases plasma triglyceride and glucose levels and modifies lipoprotein profiles in KK-Ay mice. J Pharmacol Exp Ther 30: 970-977

  • 36. Murakami K, Tobe K, Ide T, Mochizuki T, Ohashi M, Akanuma Y, Yazaki Y, and Kadowaki T (1998) A novel insulin sensitizer acts as a coligand for peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and PPAR-gamma: effect of PPAR-alpha activation on abnormal lipid metabolism in liver of Zucker fatty rats. Diabetes 47: 1841-1847

  • 37. Murakami K, Ide T, Suzuki M, Mochizuki T, and Kadowaki T (1999) Evidence for direct binding of fatty acids and eicosanoids to human peroxisome proliferators-activated receptor alpha. Biochem Biophys Res Commun 260: 609-613

  • 38. Yu K, Bayona W, Kallen CB, Harding HP, Ravera CP, McMahon G, Brown M, and Lazar MA (1995) Differential activation of peroxisome proliferator-activated receptors by eicosanoids. J Biol Chem 270: 23975-23983

  • 39. Desvergne B and Wahli W (1999) Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 20: 649-688

  • 40. Rimando AM, Nagmani R, Feller DR, and Yokoyama W (2005) Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters. J Agric Food Chem 53: 3403-3407

  • 41. Kehrer JP, Biswal SS, La E, Thuiller P, Datta K, Fischer SM, and Vanden Heuvel JP (2001) Inhibition of peroxisome-proliferator-activated receptor (PPAR)alpha by MK886. Biochem J 356: 899-906

  • 42. Caira F, Antonson P, Pelto-Huikko M, Treuter E, and Gustafsson JA (2000) Cloning and characterization of RAP250, a novel nuclear receptor coactivator. J Biol Chem 275: 5308-5317

  • 43. Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, and Leid M (1997) p300 functions as a coactivator for the peroxisome proliferator-activated receptor alpha. J Biol Chem 272: 33435-33443

  • 44. Juge-Aubry CE, Kuenzli S, Sanchez JC, Hochstrasser D, and Meier CA (2001) Peroxisomal bifunctional enzyme binds and activates the activation function-1 region of the peroxisome proliferator-activated receptor alpha. Biochem J 353: 253-258

  • 45. Molnar F, Matilainen M, and Carlberg C (2005) Structural determinants of the agonist-independent association of human peroxisome proliferator-activated receptors with coactivators. J Biol Chem 280: 26543-26556

  • 46. Surapureddi S, Yu S, Bu H, Hashimoto T, Yeldandi AV, Kashireddy P, Cherkaoui-Malki M, Qi C, Zhu YJ, Rao MS, et al. (2002) Identification of a transcriptionally active peroxisome proliferator-activated receptor alpha-interacting cofactor complex in rat liver and characterization of PRIC285 as a coactivator. Proc Natl Acad Sci USA 99: 11836-11841

  • 47. Tien ES, Davis JW, and Vanden Heuvel JP (2004) Identification of the CREB-binding protein/p300-interacting protein CITED2 as a peroxisome proliferator-activated receptor alpha coregulator. J Biol Chem 279: 24053-24063

  • 48. Vega RB, Huss JM, and Kelly DP (2000) The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol 20: 1868-1876

  • 49. Zhou G, Cummings R, Li Y, Mitra S, Wilkinson HA, Elbrecht A, Hermes JD, Schaeffer JM, Smith RG, and Moller DE (1998) Nuclear receptors have distinct affinities for coactivators: characterization by fluorescence resonance energy transfer. Mol Endocrinol 12: 1594-1604

  • 50. Zhu Y, Qi C, Calandra C, Rao MS, and Reddy JK (1996) Cloning and identification of mouse steroid receptor coactivator-1 (mSRC-1), as a coactivator of peroxisome proliferator-activated receptor gamma. Gene Expr 6: 185-195

  • 51. Zhu Y, Qi C, Jain S, Rao MS, and Reddy JK (1997) Isolation and characterization of PBP, a protein that interacts with peroxisome proliferator-activated receptor. J Biol Chem 272: 25500-25506

  • 52. Zhu Y, Kan L, Qi C, Kanwar YS, Yeldandi AV, Rao MS, and Reddy JK (2000) Isolation and characterization of peroxisome proliferator-activated receptor (PPAR) interacting protein (PRIP) as a coactivator for PPAR. J Biol Chem 275: 13510-13516

  • 53. DiRenzo J, Soderstrom M, Kurokawa R, Ogliastro MH, Ricote M, Ingrey S, Horlein A, Rosenfeld MG, and Glass CK (1997) Peroxisome proliferator-activated receptors and retinoic acid receptors differentially control the interactions of retinoid X receptor heterodimers with ligands, coactivators, and corepressors. Mol Cell Biol 17: 2166-2176

  • 54. Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, and Leid M (1999) Identification of nuclear receptor corepressor as a peroxisome proliferator-activated receptor alpha interacting protein. J Biol Chem 274: 15901-15907

  • 55. Joyeux A, Cavailles V, Balaguer P, and Nicolas JC (1997) RIP 140 enhances nuclear receptor-dependent transcription in vivo in yeast. Mol Endocrinol 11: 193-202

  • 56. Miyata KS, McCaw SE, Meertens LM, Patel HV, Rachubinski RA, and Capone JP (1998) Receptor-interacting protein 140 interacts with and inhibits transactivation by, peroxisome proliferator-activated receptor alpha and liver-X-receptor alpha. Mol Cell Endocrinol 146: 69-76

  • 57. Yan ZH, Karam WG, Staudinger JL, Medvedev A, Ghanayem BI, and Jetten AM (1998) Regulation of peroxisome proliferator-activated receptor alpha-induced transactivation by the nuclear orphan receptor TAK1/TR4. J Biol Chem 273: 10948-10957

  • 58. Gearing KL, Crickmore A, and Gustafsson JA (1994) Structure of the mouse peroxisome proliferator activated receptor alpha gene. Biochem Biophys Res Commun 199: 255-263

  • 59. Gervois P, Torra IP, Chinetti G, Grotzinger T, Dubois G, Fruchart JC, Fruchart-Najib J, Leitersdorf E, and Staels B (1999) A truncated human peroxisome proliferator-activated receptor alpha splice variant with dominant negative activity. Mol Endocrinol 13: 1535-1549

  • 60. Issemann I, Prince R, Tugwood J, and Green S (1992) A role for fatty acids and liver fatty acid binding protein in peroxisome proliferation? Biochem Soc Trans 20: 824-827

  • 61. Marcus SL, Miyata KS, Zhang B, Subramani S, Rachubinski RA, and Capone JP (1993) Diverse peroxisome proliferator-activated receptors bind to the peroxisome proliferator-responsive elements of the rat hydratase/dehydrogenase and fatty acyl-CoA oxidase genes but differentially induce expression. Proc Natl Acad Sci USA 90: 5723-5727

  • 62. Tugwood JD, Issemann I, Anderson RG, Bundell KR, McPheat WL, and Green S (1992) The mouse peroxisome proliferator activated receptor recognizes a response element in the 5′ flanking sequence of the rat acyl CoA oxidase gene. EMBO (Eur Mol Biol Organ) J 11: 433-439

  • 63. Brandt JM, Djouadi F, and Kelly DP (1998) Fatty acids activate transcription of the muscle carnitine palmitoyltransferase I gene in cardiac myocytes via the peroxisome proliferator-activated receptor alpha. J Biol Chem 273: 23786-23792

  • 64. Mascaro C, Acosta E, Ortiz JA, Marrero PF, Hegardt FG, and Haro D (1998) Control of human muscle-type carnitine palmitoyltransferase I gene transcription by peroxisome proliferator-activated receptor. J Biol Chem 273: 8560-8563

  • 65. Yu GS, Lu YC, and Gulick T (1998) Co-regulation of tissue-specific alternative human carnitine palmitoyltransferase Ibeta gene promoters by fatty acid enzyme substrate. J Biol Chem 273: 32901-32909

  • 66. Gulick T, Cresci S, Caira T, Moore DD, and Kelly DP (1994) The peroxisome proliferator-activated receptor regulates mitochondrial fatty acid oxidative enzyme gene expression. Proc Natl Acad Sci USA 91: 11012-11016

  • 67. Kersten S, Mandard S, Tan NS, Escher P, Metzger D, Chambon P, Gonzalez FJ, Desvergne B, and Wahli W (2000) Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene. J Biol Chem 275: 28488-28493

  • 68. Frohnert BI, Hui TY, and Bernlohr DA (1999) Identification of a functional peroxisome proliferator-responsive element in the murine fatty acid transport protein gene. J Biol Chem 274: 3970-3977

  • 69. Vu-Dac N, Schoonjans K, Kosykh V, Dallongeville J, Fruchart JC, Staels B, and Auwerx J (1995) Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. J Clin Investig 96: 741-750

  • 70. Zandbergen F, Mandard S, Escher P, Tan NS, Patsouris D, Jatkoe T, Rojas-Caro S, Madore S, Wahli W, Tafuri S, et al. (2005) The G0/G1 switch gene 2 is a novel PPAR target gene. Biochem J 392: 313-324

  • 71. Guerre-Millo M, Rouault C, Poulain P, Andre J, Poitout V, Peters JM, Gonzalez FJ, Fruchart JC, Reach G, and Staels B (2001) PPAR-alpha-null mice are protected from high-fat diet-induced insulin resistance. Diabetes 50: 2809-2814

  • 72. Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, and Wahli W (1999) Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Investig 103: 1489-1498

  • 73. Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, Fernandez-Salguero PM, Westphal H, and Gonzalez FJ (1995) Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol 15: 3012-3022

  • 74. Leone TC, Weinheimer CJ, and Kelly DP (1999) A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders. Proc Natl Acad Sci USA 96: 7473-7478

  • 75. Michalik L, Desvergne B, Tan NS, Basu-Modak S, Escher P, Rieusset J, Peters JM, Kaya G, Gonzalez FJ, Zakany J, et al. (2001) Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)alpha and PPARbeta mutant mice. J Cell Biol 154: 799-814

  • 76. Patel DD, Knight BL, Wiggins D, Humphreys SM, and Gibbons GF (2001) Disturbances in the normal regulation of SREBP-sensitive genes in PPAR alpha-deficient mice J Lipid Res 42: 328-337

  • 77. Finck BN, Lehman JJ, Leone TC, Welch MJ, Bennett MJ, Kovacs A, Han X, Gross RW, Kozak R, Lopaschuk GD, et al. (2002) The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Investig 109: 121-130

  • 78. Park SY, Cho YR, Finck BN, Kim HJ, Higashimori T, Hong EG, Lee MK, Danton C, Deshmukh S, Cline GW, et al. (2005) Cardiac-specific overexpression of peroxisome proliferator-activated receptor-alpha causes insulin resistance in heart and liver. Diabetes 54: 2514-2524

  • 79. Finck BN, Bernal-Mizrachi C, Han DH, Coleman T, Sambandam N, LaRiviere LL, Holloszy JO, Semenkovich CF, and Kelly DP (2005) A potential link between muscle peroxisome proliferator- activated receptor-alpha signaling and obesity-related diabetes. Cell Metab 1: 133-144

  • 80. Michalik L, Feige JN, Gelman L, Pedrazzini T, Keller H, Desvergne B, and Wahli W (2005) Selective expression of a dominant negative form of PPAR in keratinocytes leads to impaired epidermal healing. Mol Endocrinol 19: 2335-2348

  • 81. Kersten S, Desvergne B, and Wahli W (2000) Roles of PPARs in health and disease. Nature (Lond) 405: 421-424

  • 82. Kockx M, Gervois PP, Poulain P, Derudas B, Peters JM, Gonzalez FJ, Princen HM, Kooistra T, and Staels B (1999) Fibrates suppress fibrinogen gene expression in rodents via activation of the peroxisome proliferator-activated receptor-alpha. Blood 93: 2991-2998