Nuclear receptors in metabolic diseases

Expert Opinion on Therapeutic Targets

Volumn 4, Issue 3, 2000, Pages 377-396

  Mukherjee, Ranjan ^a   Saye, Jo Anne ^a   Young, Peter R ^a  

^a DUPONT COMPANY   (United States)

Author keywords

diabetes; dyslipidaemia; FXR; HNF4; LXR; nuclear receptors; obesity; PPAR

Indexed keywords

EID: 0001541715     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.4.3.377     Document Type: Review

References (156)

1. REAVEN GM: Role of insulin resistance in human disease. Diabetes (1988) 37:1595-1607. (Pubitemid 19004941)
2. REAVEN GM: Syndrome X: 6 years later. J. Intern. Med. (1994) 236:13-22.
3. HANSEN BC: The metabolic syndrome X. NY Acad. Sci. (1999) 892:1-24.
4. SCHMIDT MI, WATSON RL, DUNCAN B et al.: Clustering of dyslipidemia, hyperuricemia, diabetes and hypertension and its association with fasting insulin and central and overall obesity in a general population. Metabolism (1996) 45:699-706. (Pubitemid 26176111)
5. BARZILAI N, GUPTA G: Interaction between aging and syndrome X: new insights on the pathophysiology of fat distribution. NY Acad. Sci. (1999) 892:58-72.
6. KISSEBAH AH, KRAKOWER GR: Regional adiposity and morbidity. Physiol. Rev. (1994) 74:761-811. (Pubitemid 24328939)
7. DEFRONZO RA: Insulin resistance, hyperinsulinemia and coronary artery disease: a complex metabolic web. J. Cardiovasc. Pharm. (1992) 20:S1-S16.
8. HANSEN BC, JEN K-L, SCHWARTZ J: Changes in insulin response and binding in adipocytes from monkeys with obesity progressing to diabetes. Int. J. Obes. (1988) 12:391-401.
9. BRAY GA, TARTAGLIA LA: Medicinal strategies in the treatment of obesity. Nature (2000) 404:672-677. (Pubitemid 30205072)
10. GREENWAY FL, RYAN DH, BRAY GA, ROOD JC, TUCKER EW, SMITH SR: Pharmaceutical cost savings of treating obesity with weight loss medications. Obes. Res. (1999) 7:523-531. (Pubitemid 129710616)
11. KOPELMAN PG: Obesity as a medical problem. Nature (2000) 404:635-643. (Pubitemid 30205068)
12. KHAODHIAR L, MCCOWEN K, BLACKBURN G: Obesity and its comorbid conditions. Clin. Cornerstone (1999) 2:17-31.
13. GOLDSTEIN D, TRAUTMANN M: Treatments for obesity. Emerging Drugs (1997) 2:1-27. (Pubitemid 28059842)
14. WOLF AM, COLDITZ GA: Current estimates of the economic cost of obesity in the United States. Obes. Res. (1998) 6:97-106. (Pubitemid 128679649)
15. ROSENBAUM M, LEIBEL RL, HIRSCH J: Obesity. N. Engl. J. Med. (1997) 6:396-407.
16. MORRICONE L, FERRARI M, ENRINI R et al.: The role of central fat distribution in coronary artery disease in obesity: comparison of nondiabetic obese, diabetic obese and normal weight subjects. Int. J. Obes. (1999) 23:1129-1135.
17. KAMEL EG, MCNEILL G, VAN WIJK MCW: Usefulness of anthropometry and DXA in predicting intraabdominal fat in obese men and women. Obes. Res. (1999) 8:36-42.
18. CLASEY JL, BOUCHARD C, TEATES CD et al.: The use of anthropometric and dual-energy X-ray absorptiometry (DXA) measures to estimate total abdominal and abdominal visceral fat in men and women. Obes. Res. (1999) 7:256-264. (Pubitemid 129710584)
19. ARNER P: Differences in lipolysis between human subcutaneous and omental adipose tissues. Ann. Med. (1995) 27:435-438.
20. MALCHOFF DM, MELOFF BL, LIVINGSTON JN, LOCKWOOD DH: Influence of dexamethasone on insulin action: inhibition on basal and insulinstimulated hexose transport is dependent on length of exposure in vitro. Endocrinology (1982) 110:2081-2087.
21. DE MAZANCOURT P, GIOT J, GIUDICELLI Y: Correction by dexamethasone treatment of the altered lipolytic cascade induce by adrenalectomy in rat adipocytes. Horm. Metab. Res. (1990) 22:22-24. (Pubitemid 20041386)
22. GOLAY A, FELBER J-P, JEQUIER E, DEFRONZO RA, FERRANNINI E: Metabolic basis of obesity and noninsulin-dependent diabetes mellitus. Diabetes Metab. Rev. (1988) 4:727-747. (Pubitemid 19019240)
23. WAHL PW, SAVAGE PJ, PSATY BM, ORCHARD TJ, ROBBINS JA, TRACY RP: Diabetes in older adults: comparison of 1997 American Diabetes Association classification of diabetes mellitus with 1985 WHO classification. Lancet (1998) 352:1012-1015. (Pubitemid 28438572)
24. EVERHEART JE, PETTITT DJ, BENNETT PH, KNOWLER WC: Duration of obesity increased the incidences of NIDDM. Diabetes (1992) 41:235-240.
25. COLDITZ G, A, WILLETT WC, ROTNITSKY A, MANSON JE: Weight gain as a risk factor for clinical diabetes in women. Arch. Int. Med. (1995) 122:481-486.
26. CHAN HN: Obesity, fat distribution and weight gain as risk factors for clinical diabetes in men. Diabetes Care (1994) 17:961-969.
27. GENUTH S: Implications of the United Kingdom Prospective Diabetes Study for patients with obesity and Type 2 diabetes. Obes. Res. (2000) 8:198-201.
28. COLLINS RW, ANDERSON JW: Medication cost savings associated with weight loss for obese non-insulindependent diabetic men and women. Prev. Med. (1995) 24:369-374.
29. HERMAN WH, DASBACH EJ, SONGER TJ, EASTMAN RC: The cost-effectiveness of intensive therapy for diabetes mellitus. Endocrinol. Metab. Clin. North Am. (1997) 26:675-695.
30. CUELLAR GEM, RUIZ AM, MONSALVE MCR, BERGER A: Six-month treatment of obesity with sibutramine 15 mg; a double-blind. placebo-controlled monocenter clinical trial in a hispanic population. Obes. Res. (2000) 8:71-82.
31. MCNEELY W, GOA K: Sibutramine: a review of its contribution to the management of obesity. Drugs (1998) 56:1093-1024.
32. ROLLS BJ, SHIDE DJ, THORWART M, ULBRECHT JS: Sibutramine reduces food intake in non-dieting women with obesity. Obes. Res. (1998) 6:1-11. (Pubitemid 128679638)
33. SEAGLE HM, BESSESEN DH, HILL JO: Effects of sibutramine on resting metabolic rate and weight loss in overweight women. Obes. Res. (1998) 6:115-121. (Pubitemid 128679651)
34. FANGHANEL G, CORTINAS L, SANCHEZ-REYES L, BERBER A: A clinical trial of the use of sibutramine for the treatment of patients suffering essential obesity. Int. J. Obes. (2000) 24:144-150. (Pubitemid 30107561)
35. LEAN M: Sibutramine-a review of clinical efficacy. Int. J. Obes. (1997) 21:S30-S36.
36. GUERCIOLLINI R: Mode of action of orlistat. Int. J. Obes. (1997) 21(Suppl. 3):S12-S23.
37. ROSSNER S, SJOSTROM L, NOACK R, MEINDERS EA, NOSEDA G: Weight loss, weight maintenance and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. Obes. Res. (2000) 8:49-61.
38. BROWN D, BRILLON D: New directions in Type 2 diabetes mellitus: an update of current oral antidiabetic therapy. J. Natl. Med. Assoc. (1999) 91:389-395.
39. GOMIS R: Repaglinide as monotherapy in Type 2 diabetes. Exp. Clin. Endocrinol. Diabetes (1999) 107 (Suppl. 4):S133-135. (Pubitemid 29457106)
40. WIERNSPERGER NF, BAILEY CJ: The antihyperglycaemic effect of metformin: therapeutic and cellular mechanisms. Drugs (1999) 58(Suppl. 1):31-39. (Pubitemid 129758579)
41. TURNER NC: New therapeutic agents for the treatment of insulin resistance and NIDDM. Drug Disc. Today (1996) 1:109-116. (Pubitemid 126402347)
42. WIERNSPERGER NF, BAILEY CJ: The antihyperglycaemic effect of metformin therapeutic and cellular mechanisms. Drugs (1999) 58:31-39. (Pubitemid 129758579)
43. LEHMANN JM, MOORE LB, SMITH-OLIVER TA, WILKISON WO, WILLSON TM, KLIEWER SA: An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J. Biol. Chem. (1995) 270:12953-12956.
44. WILLSON TM, COBB JE, COWAN DJ et al.: The structureactivity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones. J. Med. Chem. (1996) 39:665-668.
45. YU JG, KRUSZYNSKA YT, MULFORD MI, OLEFSKY JM: A comparison of troglitazone and metformin on insulin requirements in euglycemic intensively insulintreated Type 2 diabetic patients. Diabetes (1999) 48:2414-2421. (Pubitemid 30395434)
46. BALFOUR JAB, PLOSKER GL: Rosiglitazone. Drugs (1999) 2:921-930. (Pubitemid 29313203)
47. LENHARD JM, KLIEWER SA, PAULIK MA, PLUNKET KD, LEHMANN JM, WEIEL JE: Effects of troglitazone and metformin on glucose and lipid metabolism: alterations of two distinct molecular pathways. Biochem. Pharmacol. (1997) 54:801-808. (Pubitemid 27404681)
48. LEFEBVRE AM, PEINADO-ONSURBE J, LEITERSDORF I et al.: Regulation of lipoprotein metabolism by thiazolidinediones occurs through a distinct but complementary mechanism relative to fibrates. Arterioscler. Thromb. Vasc. Biol. (1997) 17:1756-1764. (Pubitemid 27423998)
49. NUCLEAR RECEPTORS COMMITTEE: A unified nomenclature system for the nuclear receptor subfamily. Cell (1999) 97:1-20.
50. ROBYR D, WOLFFE AP, WAHLI W: Nuclear hormone receptor coregulators in action: diversity for shared tasks. Mol. Endocrinol. (2000) 14:329-347. (Pubitemid 32266074)
51. GLASS CK, ROSENFELD MG: The coregulator exchange intranscriptional functions of nuclear receptors. Genes Dev. (2000) 14:121-141. (Pubitemid 30070977)
52. KREY G, BRAISSANT O, L'HORSET F et al.: Fatty acids, eicosanoids and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Mol. Endocrinol. (1997) 11:779-791. (Pubitemid 27225305)
53. ZHOU G, CUMMINGS R, LI Y et al.: Nuclear receptors have distinct affinities for coactivators: characterization by fluorescence resonance energy transfer. Mol. Endocrinol. (1998) 12:1594-1604. (Pubitemid 30663441)
54. SPIEGELMAN B, WU Z, PUGSERVER P: Control of adipogenesis and energy balance through PPARgamma and novel coactivators. Keystone Symposia on Nuclear Receptors. Taos, USA (2000) Abstract 012.
55. PARKS DJ, BLANCHARD SG, BLEDSOE RK et al.: Bile acids: natural ligands for an orphan nuclear receptor [see comments]. Science (1999) 284:1365-1368. (Pubitemid 29289664)
56. ISSEMAN I, GREEN S: Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature (1990) 347:645-650.
57. DREYER C, KREY G, KELLER H, GIVEL F, HELFTENBEIN G, WAHLI W: Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell (1992) 68:879-887.
58. SCHMIDT A, ENDO N, 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.
59. AMRI EZ, BONINO F, AILHAUD G, ABUMRAD NA, GRIMALDI PA: Cloning of a protein that mediates transcriptional effects of fatty acids in preadipocytes. Homology to peroxisome proliferator-activated receptors. J. Biol. Chem. (1995) 270:2367-2371.
60. KLIEWER SA, FORMAN BM, BLUMBERG B et al.: Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc. Natl. Acad. Sci. USA (1994) 91:7355-7359. (Pubitemid 24226862)
61. KLIEWER SA, UMESONO K, NOONAN DJ, HEYMAN RA, EVANS RM: Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature (1992) 358:771-774.
62. MIYATA KS, MCCAW SE, PATEL HV, RACHUBINSKI RA, CAPONE JP: The orphan nuclear hormone receptor LXR alpha interacts with the peroxisome proliferatoractivated receptor and inhibits peroxisome proliferator signaling. J. Biol. Chem. (1996) 271:9189-9192. (Pubitemid 26137316)
63. BOGAZZI F, HUDSON LD, NIKODEM VM: A novel heterodimerization partner for thyroid hormone receptor. Peroxisome proliferator-activated receptor. J. Biol. Chem. (1994) 269:11683-11686.
64. SCHOONJANS K, STAELS B, AUWERX J: Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J. Lipid Res. (1996) 37:907-925. (Pubitemid 26182326)
65. RICOTE M, LI AC, WILLSON TM, KELLY CJ, GLASS CK: The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature (1998) 391:79-82. (Pubitemid 28079218)
66. STAELS B, KOENIG W, HABIB A et al.: Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators. Nature (1998) 393:790-793. (Pubitemid 28299490)
67. DELERIVE 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-kappaB and AP-1. J. Biol. Chem. (1999) 274:32048-32054.
68. MUKHERJEE et al.: Abstracts of the Keystone Conference on PPARs. (1999) pp:30. Abstract 112.
69. LEE SS, PINEAU T, DRAGO J et al.: Targeted disruption of the alpha isoform of the peroxisome proliferatoractivated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol. Cell Biol. (1995) 15:3012-3022.
70. GOTTLICHER M, WIDMARK E, LI Q, GUSTAFSSON JA: Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. Proc. Natl. Acad. Sci. USA (1992) 89:4653-4657.
71. KLIEWER SA, SUNDSETH SS, JONES SA et al.: Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferatoractivated receptors alpha and gamma. Proc. Natl. Acad. Sci. USA (1997) 94:4318-4323. (Pubitemid 27194239)
72. BROWN PJ, WINEGAR DA, PLUNKET KD et al.: A ureidothioisobutyric acid (GW9578) is a subtype-selective PPARalpha agonist with potent lipid-lowering activity. J. Med. Chem. (1999) 42:3785-3788. (Pubitemid 29453459)
73. WILLSON TM, BROWN PJ, STERNBACH DD, HENKE BR: The PPARs: from orphan receptors to drug discovery. J. Med. Chem. (2000) 43:527-550. (Pubitemid 30127149)
74. STAELS B, DALLONGEVILLE J, AUWERX J, SCHOONJANS K, LEITERSDORF E, FRUCHART JC: Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation (1998) 98:2088-2093. (Pubitemid 28512236)
75. RUBINS BLOOMFIELD H, ROBINS SJ et al.: Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N. Engl. J. Med. (1999) 341:410-418. (Pubitemid 29362514)
76. JIN F-Y, KAMANNA VS, CHUANG M-Y, MORGAN K, KASHYAP ML: Gemfibrozil stimulates apolipoprotein A-I synthesis and secretion by stabilization of mRNA transcripts in human hepatoblastoma cell line (HEP G2). Arterioscler. Thromb. Vasc. Biol. (1996) 16:1052-1062. (Pubitemid 26266907)
77. HENNUYER N, POULAIN P, MADSEN L et al.: Beneficial effects of fibrates on apolipoprotein A-I metabolism occur independently of any peroxisome proliferative response. Circulation (1999) 99:2445-2451. (Pubitemid 29218242)
78. MARX N, SUKHOVA GK, COLLINS T, LIBBY P, PLUTZKY J: PPARalpha activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Circulation (1999) 99:3125-3131. (Pubitemid 29289077)
79. GUERRE-MILLO M, GERVOIS P, RASPE E et al.: Peroxisome Proliferator-Activated Receptor activators improve insulin sensitivity and reduce adiposity. J. Biol. Chem. (2000) 275: 16638-16642. (Pubitemid 30398891)
80. 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) 274:6718-6725. (Pubitemid 29111093)
81. 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) 94:4312-4317. (Pubitemid 27194238)
82. LEIBOWITZ: Abstracts of the Keystone Symposia on the PPARs. (1999) pp25 Abstract 009.
83. JOW L, MUKHERJEE R: The human peroxisome proliferator-activated receptor (PPAR) subtype NUC1 represses the activation of hPPAR alpha and thyroid hormone receptors. J. Biol. Chem. (1995) 270:3836-3840.
84. HE TC, CHAN TA, VOGELSTEIN B, KINZLER KW: PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell (1999) 99:335-345. (Pubitemid 29519912)
85. MUKHERJEE R, JOW L, CROSTON GE, PATERNITI JR, JR.: Identification, characterization and tissue distribution of human peroxisome proliferator-activated receptor (PPAR) isoforms PPARgamma2 versus PPARgamma1 and activation with retinoid X receptor agonists and antagonists. J. Biol. Chem. (1997) 272:8071-8076. (Pubitemid 27137374)
86. FAJAS L, FRUCHART JC, AUWERX J: PPARgamma3 mRNA: a distinct PPARgamma mRNA subtype transcribed from an independent promoter. FEBS Lett. (1998) 438:55-60. (Pubitemid 28517834)
87. TONTONOZ P, NAGY L, ALVAREZ JG, THOMAZY VA, EVANS RM: PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell (1998) 93:241-252. (Pubitemid 28180857)
88. SHIMOMURA I, HAMMER RE, RICHARDSON JA et al.: Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev. (1998) 12:3182-3194. (Pubitemid 28496263)
89. MOITRA J, MASON MM, OLIVE Met al.: Life without white fat: a transgenic mouse. Genes Dev. (1998) 12:3168-3181. (Pubitemid 28496262)
90. TONTONOZ P, HU E, SPIEGELMAN BM: Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipidactivated transcription factor [published erratum appears in Cell (1995) 80(6):following 957]. Cell (1994) 79:1147-1156.
91. NAGY L, TONTONOZ P, ALVAREZ JG, CHEN H, EVANS RM: Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma. Cell (1998) 93:229-240. (Pubitemid 28180856)
92. KLIEWER SA, LENHARD JM, WILLSON TM, PATEL I, MORRIS DC, LEHMANN JM: A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell (1995) 83:813-819. (Pubitemid 3006325)
93. FORMAN BM, TONTONOZ P, CHEN J, BRUN RP, SPIEGELMAN BM, EVANS RM: 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell (1995) 83:803-812. (Pubitemid 3006324)
94. MUKHERJEE R, DAVIES PJ, CROMBIE DL et al.: Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists. Nature (1997) 386:407-410. (Pubitemid 27154482)
95. HALLAKOU S, FOUFELLE F, DOARE L, KERGOAT M, FERRE P: Pioglitazone-induced increase of insulin sensitivity in the muscles of the obese Zucker fa/fa rat cannot be explained by local adipocyte differentiation. Diabetologia (1998) 41:963-968. (Pubitemid 28365984)
96. OKUNO A, TAMEMOTO H, TOBE K et al.: Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J. Clin. Invest. (1998) 101:1354-1361. (Pubitemid 28145252)
97. MURAKAMI K, TOBE K, IDE T et al.: 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 (1998) 47:1841-1847. (Pubitemid 28549189)
98. KUBOTA N, TERAUCHI Y, MIKI H et al.: PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol. Cell (1999) 4:597-609. (Pubitemid 29531139)
99. BARAK Y, NELSON MC, ONG ES et al.: PPAR gamma is required for placental, cardiac and adipose tissue development. Mol. Cell (1999) 4:585-595. (Pubitemid 29531138)
100. RISTOW M, MULLER-WIELAND D, PFEIFFER A, KRONE W, KAHN CR: Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. N. Engl. J. Med. (1998) 339:953-959. (Pubitemid 28455097)
101. DEEB SS, FAJAS L, NEMOTO Met al.: A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nature Genet. (1998) 20:284-287. (Pubitemid 28507675)
102. REGINATO MJ, BAILEY ST, KRAKOW SL et al.: A potent antidiabetic thiazolidinedione with unique peroxisome proliferator-activated receptor gammaactivating properties. J. Biol. Chem. (1998) 273:32679-32684. (Pubitemid 28557651)
103. REDDY KA, LOHRAY BB, BHUSHAN V et al.: Novel antidiabetic and hypolipidemic agents. 5. Hydroxyl versus benzyloxy containing chroman derivatives. J. Med. Chem. (1999) 42:3265-3278. (Pubitemid 29409715)
104. CAMP HS, LI O, WISE SC et al.: Differential activation of peroxisome proliferator-activated receptor-y by troglitazone and rosiglitazone. Diabetes (2000) 49:539-547. (Pubitemid 30183741)
105. SHIMAYA A, KUROSAKI E, NAKANO R, HIRAYAMA R, SHIBASAKI M, SHIKAMA H: The novel hypoglycemic agent YM440 normalized hyperglycemia without changing body fat weight in diabetic db/db mice. Metabolism (2000) 49:411-417. (Pubitemid 30146575)
106. OAKES ND, CAMILLERI S, FURLER SM, CHISHOLM DJ, KRAEGEN EW: The insulin sensitizer, BRL 49653, reduces systemic fatty acid supply and utilization and tissue lipid availability in the rat. Metabolism (1997) 46:935-942. (Pubitemid 27339920)
107. MARTIN G, SCHOONJANS K, LEFEBVRE AM, STAELS B, AUWERX J: Coordinate regulation of the expression of the fatty acid transport protein and acyl-CoA synthetase genes by PPARalpha and PPARgamma activators. J. Biol. Chem. (1997) 272:28210-28217. (Pubitemid 27517759)
108. NOLTE RT, WISELY GB, WESTIN S et al.: Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature (1998) 395:137-143. (Pubitemid 28425645)
109. UPPENBERG J, SVENSSON C, JAKI M, BERTILSSON G, JENDEBERG L, BERKENSTAM A: Crystal structure of the ligand binding domain of the human nuclear receptor PPARgamma. J. Biol. Chem. (1998) 273:31108-31112. (Pubitemid 28533120)
110. GAMPE RT, MONTANA VG, LAMBERT MH, KLIEWER SA, WILLSON TM, XU HE: Asymmetry in the PPARy/RXRa crystal structure reveals the molecular basis of heterodimerization among nuclear receptors. Mol. Cell (2000) 5:545-555.
111. JIANG C, TING AT, SEED B: PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature (1998) 391:82-86. (Pubitemid 28079219)
112. SU CG, WEN X, BAILEY ST et al.: A novel therapy for colitis utilizing PPAR-gamma ligands to inhibit the epithelial inflammatory response. J. Clin. Invest. (1999) 104:383-389. (Pubitemid 29534322)
113. RICOTE M, HUANG J, FAJAS L et al.: Expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein. Proc. Natl. Acad. Sci. USA (1998) 95:7614-7619.
114. ALTIOK S, XU M, SPIEGELMAN BM: PPARgamma induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A. Genes Dev. (1997) 11:1987-1998. (Pubitemid 27332985)
115. DEMETRI GD, FLETCHER CD, MUELLER E et al.: Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc. Natl. Acad. Sci. USA (1999) 96:3951-3956. (Pubitemid 29169017)
116. KUBOTA T, KOSHIZUKA K, WILLIAMSON EA et al.: Ligand for peroxisome proliferator-activated receptor gamma (troglitazone) has potent antitumor effect against human prostate cancer both in vitro and in vivo. Cancer Res. (1998) 58:3344-3352. (Pubitemid 28371075)
117. ELSTNER E, MULLER C, KOSHIZUKA K et al.: Ligands for peroxisome proliferator-activated receptor gamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNXmice. Proc. Natl. Acad. Sci. USA (1998) 95:8806-8011.
118. SARRAF P, MUELLER E, JONES D et al.: Differentiation and reversal of malignant changes in colon cancer through PPARgamma [see comments]. Nature Med. (1998) 4:1046-1052. (Pubitemid 28417337)
119. SAEZ E, TONTONOZ P, NELSON MC et al.: Activators of the nuclear receptor PPARgamma enhance colon polyp formation. Nature Med. (1998) 4:1058-1061. (Pubitemid 28417339)
120. LEFEBVRE AM, CHEN I, DESREUMAUX P et al.: Activation of the peroxisome proliferator-activated receptor gamma promotes the development of colon tumors in C57BL/6J-APCMin/+ mice. Nature Med. (1998) 4:1053-1057. (Pubitemid 28417338)
121. SAMID D, SHACK S, SHERMAN LT: Phenylacetate: a novel nontoxic inducer of tumor cell differentiation. Cancer Res. (1992) 52:1988-1992.
122. SAMID D, WELLS M, GREENE ME, SHEN W, PALMER CNA, THIBAULT A: Peroxisome proliferator-activated receptor as a novel target in cancer therapy: binding and activation by an aromatic fatty acid with clinical antitumor activity. Clin. Cancer Res. (2000) 6:933-941. (Pubitemid 30159351)
123. CHIANG JYL: Regulation of bile acid synthesis. Frontiers Biosci. (1998) 3:176-193.
124. SIPPEL CJ, DAWSON PA, SHEN T, PERLMUTTER DH: Reconstitution of bile acid transport in a heterologous cell by cotransfection of transporters for bile acid uptake and efflux. J. Biol. Chem. (1997) 272:18290-18297. (Pubitemid 27306419)
125. SHNEIDER BL: Expression cloning of the ileal sodiumdependent bile acid transporter. J. Pediatr. Gastroenterol. Nutr. (1995) 20:233-235.
126. GONG YZ, EVERETT ET, SCHWARTZ DA, NORRIS JS, WILSON FA: Molecular cloning, tissue distribution and expression of a 14-kDa bile acid-binding protein from rat ileal cytosol. Proc. Natl. Acad. Sci. USA (1994) 91:4741-4745. (Pubitemid 24177725)
127. KIM RB, LEAKE B, CVETKOVIC M et al.: Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity. J. Pharmacol. Exp. Ther. (1999) 291:1204-1209.
128. KULLAK-UBLICK GA, BEUERS U, PAUMGARTNER G: Molecular and functional characterization of bile acid transport in human hepatoblastoma HepG2 cells. Hepatology (1996) 23:1053-1060. (Pubitemid 26137046)
129. DOERNER KC, GURLEY EC, VLAHCEVIC ZR, HYLEMON PB: Regulation of cholesterol 7 alpha-hydroxylase expression by sterols in primary rat hepatocyte cultures. J. Lipid Res. (1995) 36:1168-1177.
130. CHIANG JY, STROUP D: Identification and characterization of a putative bile acid-responsive element in cholesterol 7 alpha-hydroxylase gene promoter. J. Biol. Chem. (1994) 269:17502-17507. (Pubitemid 24218029)
131. TWISK J, DE WITT ECM, PRINCEN HMG: Suppression of sterol 27-hydroxylase mRNA and transcriptional activity by bile acids in cultured rat hepatocytes. Biochem. J. (1995) 305:505-511.
132. WILLY PJ, UMESONO K, ONG ES, EVANS RM, HEYMAN RA, MANGELSDORF DJ: LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev. (1995) 9:1033-1045.
133. JANOWSKI BA, WILLY PJ, DEVI TR, FALCK JR, MANGELSDORF DJ: An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature (1996) 383:728-731. (Pubitemid 26360651)
134. LEHMANN JM, KLIEWER SA, MOORE LB et al.: Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J. Biol. Chem. (1997) 272:3137-3140. (Pubitemid 27066798)
135. JANOWSKI BA, GROGAN MJ, JONES SA et al.: Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta. Proc. Natl. Acad. Sci. USA (1999) 96:266-271. (Pubitemid 29036088)
136. PEET DJ, TURLEY SD, MA W et al.: Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha. Cell (1998) 93:693-704. (Pubitemid 28257577)
137. LUO Y, TALL AR: Sterol upregulation of human CETP expression in vitro and in transgenic mice by an LXR element. J. Clin. Invest. (2000) 105:513-520. (Pubitemid 30127252)
138. HAYEK T, MASUCCI-MAGOULAS L, JIANG X et al.: Decreased early atherosclerotic lesions in hypertriglyceridemic mice expressing cholesterol ester transfer protein transgene. J. Clin. Invest. (1995) 96:2071-2071.
139. LALA DS, SYKA PM, LAZARCHIK SB, MANGELSDORF DJ, PARKER KL, HEYMAN RA: Activation of the orphan nuclear receptor steroidogenic factor 1 by oxysterols. Proc. Natl. Acad. Sci. USA (1997) 94:4895-4900. (Pubitemid 27214707)
140. NITTA M, KU S, BROWN C, OKAMOTO AY, SHAN B: CPF: an orphan nuclear receptor that regulates liverspecific expression of the human cholesterol 7alphahydroxylase gene. Proc. Natl. Acad. Sci. USA (1999) 96:6660-6665. (Pubitemid 29274939)
141. LAFFITTE BA, KAST HR, NGUYEN CM, ZAVACKI AM, MOORE DD, EDWARDS PA: Identification of the DNA binding specificity and potential target genes for the farnesoid x-activated receptor. J. Biol. Chem. (2000) 275:10638-10647. (Pubitemid 30202131)
142. FORMAN BM, GOODE E, CHEN J et al.: Identification of a nuclear receptor that is activated by farnesol metabolites. Cell (1996) 81:687-693.
143. ZAVACKI AM, LEHMANN JM, SEOL W, WILLSON TM, KLIEWER SA, MOORE DD: Activation of the orphan receptor RIP14 by retinoids. Proc. Natl. Acad. Sci. USA (1997) 94:7909-7914. (Pubitemid 27343748)
144. MAKISHIMA M, OKAMOTO AY, REPA JJ et al.: Identification of a nuclear receptor for bile acids. Science (1999) 284:1362-1365. (Pubitemid 29289663)
145. WANG H, CHEN J, HOLLISTER K, SOWERS LC, FORMAN BM: Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol. Cell (1999) 3:543-553. (Pubitemid 29268438)
146. CHIANG JY, KIMMEL R, WEINBERGER C, STROUP D: Farnesoid X receptor responds to bile acids and represses cholesterol 7alpha-hydroxylase gene (CYP7A1) transcription. J. Biol. Chem. (2000) 275:10918-10924. (Pubitemid 30212727)
147. SEOL W, CHOI HS, MOORE DD: An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors. Science (1996) 272:1336-1339. (Pubitemid 26199974)
148. SEOL W, CHUNG M, MOORE DD: Novel receptor interaction and repression domains in the orphan receptor SHP. Mol. Cell Biol. (1997) 17:7126-7131. (Pubitemid 27505942)
149. LEE YK, DELL H, DOWHAN DH, HADZOPOULOUCLADARAS M, MOORE DD: The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression. Mol. Cell Biol. (2000) 20:187-195. (Pubitemid 30002560)
150. MANGELSDORF DJ, REPA J, MAKISHIMA M, LU T, JANOWSKI B: Nuclear receptors in the orphan age. Keystone Symposium on Nuclear Receptors. Steamboat Springs, USA (2000) Abstract #002.
151. KANDA T, NIOT I, FOUCAUD L et al.: Effect of bile on the intestinal bile-acid binding protein (I-BABP) expression. In vitro and in vivo studies. FEBS Lett. (1996) 384:131-134. (Pubitemid 26139789)
152. KANDA T, FOUCAND L, NAKAMURA Y et al.: Regulation of expression of human intestinal bile acid-binding protein in Caco-2 cells. Biochem. J. (1998) 330:261-265. (Pubitemid 28075749)
153. GROBER J, ZAGHINI I, FUJII H et al.: Identification of a bile acid-responsive element in the human ileal bile acid-binding protein gene. Involvement of the farnesoid X receptor/9-cis-retinoic acid receptor heterodimer. J. Biol. Chem. (1999) 274:29749-29754.
154. NISHIKAWA J-I, SAITO K, GOTO J, DAKEYAMA F, MATSUO M, NISHIHARA T: New screening methods for chemicals with hormonal activities using interaction of nuclear hormone receptor with coactivator. Toxicol. Appl. Pharmacol. (1999) 154:76-83. (Pubitemid 29042602)
155. DIAS JM, GO NF, HART CP, MATTHEAKIS LC: Genetic recombination as a reporter for screening steroid receptor agonists and antagonists. Anal. Biochem. (1998) 258:96-102. (Pubitemid 28163149)
156. BURRIS TP, PELTON PD, ZHOU L, OSBORNE MC, CRYAN E, DEMAREST KT: A novel