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Emerging Therapeutic Targets Volume 4, 2000 - Issue 3
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Review

Nuclear receptors in metabolic diseases

Ranjan Mukherjee Department of Cardiovascular Diseases, DuPont Pharmaceuticals, Experimental Station, E400/3257, Route 141 and Henry Clay Roads, Wilmington, DE 19880-0400, USA.
,
Jo Anne Saye Department of General Pharmacology, DuPont Pharmaceuticals, Wilmington, DE 19880-0400, USA.
&
Peter R Young Department of Cardiovascular Diseases, DuPont Pharmaceuticals, Experimental Station, E400/3257, Route 141 and Henry Clay Roads, Wilmington, DE 19880-0400, USA. [email protected]
Pages 377-396 | Published online: 25 Feb 2005

Bibliography

  • REAVEN GM: Role of insulin resistance in human disease. Diabetes (1988) 37:1595–1607.
  • REAVEN GM: Syndrome X: 6 years later." Intern. Med. (1994) 236:13–22.
  • HANSEN BC: The metabolic syndrome X. NY Acad. Sci. (1999) 892:1–24.
  • 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 popula-tion. Metabolism (1996) 45:699–706.
  • 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.
  • KISSEBAH AH, KRAKOWER GR: Regional adiposity and morbidity. Physiol. Rev. (1994) 74:761–811.
  • DEFRONZO RA: Insulin resistance, hyperinsulinemia and coronary artery disease: a complex metabolic web. J. Cardiovasc. Pharm. (1992) 20:S1–S16.
  • HANSEN BC, JEN K-L, SCHWARTZ J: Changes in insulin response and binding in adipocytes from monkeys with obesity progressing to diabetes. Int. .1 Obes. (1988) 12:391–401.
  • BRAY GA, TARTAGLIA LA: Medicinal strategies in the treatment of obesity. Nature (2000) 404:672–677.
  • 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.
  • KOPELMAN PG: Obesity as a medical problem. Nature (2000) 404:635–643.
  • KHAODHIAR L, MCCOWEN K, BLACKBURN G: Obesity and its comorbid conditions. Clin. Cornerstone (1999) 2:17–31.
  • GOLDSTEIN D, TRAUTMANN M: Treatments for obesity. Emerging Drugs (1997) 2:1–27.
  • WOLF AM, COLDITZ GA: Current estimates of the economic cost of obesity in the United States. Obes. Res. (1998) 6:97–106.
  • ROSENBAUM M, LEIBEL RL, HIRSCH J: Obesity. N Engl.Med. (1997) 6:396–407.
  • MORRICONE L, FERRARI M, ENRINI R et al.: The role ofcentral fat distribution in coronary artery disease in obesity: comparison of nondiabetic obese, diabetic obese and normal weight subjects. Int. I Obes. (1999) 23:1129–1135.
  • KAMEL EG, MCNEILL G, VAN WIJK MCW: Usefulness ofanthropometry and DXA in predicting intra-abdominal fat in obese men and women. Obes. Res. (1999) 8:36–42.
  • CLASEY JL, BOUCHARD C, TEATES CD et al: The use ofanthropometric and dual-energy x-ray absorpti-ometry (DXA) measures to estimate total abdominal and abdominal visceral fat in men and women. Obes. Res. (1999) 7:256–264.
  • ARNER P: Differences in lipolysis between humansubcutaneous and °mental adipose tissues. Ann. Med. (1995) 27:435–438.
  • MALCHOFF DM, MELOFF BL, LIVINGSTON JN, LOCKWOOD DH: Influence of dexamethasone on insulin action: inhibition on basal and insulin-stimulated hex ose transport is dependent on length of exposure in vitro. Endocrinology (1982) 110:2081–2087.
  • DE MAZANCOURT P, GIOT J, GIUDICELLI Y: Correctionby dexamethasone treatment of the altered lipolytic cascade induce by adrenalectomy in rat adipocytes. Horm. Metab. Res. (1990) 22:22–24.
  • 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.
  • 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.
  • EVERHEART JE, PETTITT DJ, BENNETT PH, KNOWLER WC: Duration of obesity increased the incidences of NIDDM. Diabetes (1992) 41:235–240.
  • 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.
  • CHAN HN: Obesity, fat distribution and weight gain asrisk factors for clinical diabetes in men. Diabetes Care (1994) 17: 961–969.
  • GENUTH S: Implications of the United Kingdom Prospective Diabetes Study for patients with obesity and Type 2 diabetes. Obes. Res. (2000) 8:198–201.
  • COLLINS RW, ANDERSON JW: Medication cost savings associated with weight loss for obese non-insulin-dependent diabetic men and women. Prey. Med. (1995) 24:369–374.
  • 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.
  • 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.
  • MCNEELY W, GOA K: Sibutramine: a review of itscontribution to the management of obesity. Drugs (1998) 56:1093–1024.
  • ROLLS BJ, SHIDE DJ, THORWART M, ULBRECHT JS: Sibutramine reduces food intake in non-dieting women with obesity. Obes. Res. (1998) 6:1–11.
  • SEAGLE HM, BESSESEN DH, HILL JO: Effects of sibutra-mine on resting metabolic rate and weight loss in overweight women. Obes. Res. (1998) 6:115–121.
  • FANGHANEL G, CORTINAS L, SANCHEZ-REYES L, BERBERA: A clinical trial of the use of sibutramine for the treatment of patients suffering essential obesity. Int. J. Obes. (2000) 24:144–150.
  • LEAN M: Sibutramine -a review of clinical efficacy. Int. Obes. (1997) 21:S30–S36.
  • GUERCIOLLINI R: Mode of action of orlistat. Int. j Obes. (1997) 21 (Suppl. 3):S12–S23.
  • 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.
  • BROWN D, BRILLON D: New directions in Type 2 diabetes mellitus: an update of current oral antidia-betic therapy. J. Natl. Med. Assoc. (1999) 91:389–395.
  • GOMIS R: Repaglinide as monotherapy in Type 2 diabetes. Exp. Clin. Endocrinol. Diabetes (1999) 107 (Suppl. 4):S133–135.
  • WIERNSPERGER NF, BAILEY CJ: The an tihyp er gly caem ic effect of metformin: therapeutic and cellular mechanisms. Drugs (1999) 58 (Suppl. 1):31–39.
  • TURNER NC: New therapeutic agents for the treatment of insulin resistance and NIDDM. Drug Disc. Today (1996) 1:109–116.
  • WIERNSPERGER NF, BAILEY CJ: The an tihyp er gly caem ic effect of metformin therapeutic and cellular mechanisms. Drugs (1999) 58:31–39.
  • LEHMANN JM, MOORE LB, SMITH-OLIVER TA, WILKISON WO, WILLSON TM, KLIEWER SA: An antidiabetic thiazolidinedione is a high affinity ligand for peroxi-some proliferator-activated receptor gamma (PPAR gamma). J. Biol. Chem. (1995) 270:12953–12956.
  • WILLSON TM, COBB JE, COWAN DJ et al.: The structure-activity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones. J. Med. Chem. (1996) 39:665–668.
  • YU JG, KRUSZYNSKA YT, MULFORD MI, OLEFSKY JM: Acomparison of troglitazone and metformin on insulin requirements in euglycemic intensively insulin-treated Type 2 diabetic patients. Diabetes (1999) 48:2414–2421.
  • BALFOUR JAB, PLOSKER GL: Rosiglitazone. Drugs (1999)2:921–930.
  • LENHARD JM, KLIEWER SA, PAULIK MA, PLUNKET KD, LEHMANN JM, WEIEL JE: Effects of troglitazone and metformin on glucose and lipid metabolism: altera-tions of two distinct molecular pathways. Biochem. Pharmacol. (1997) 54:801–808.
  • 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.
  • NUCLEAR RECEPTORS COMMITTEE: A unified nomenclature system for the nuclear receptor subfamily. Cell (1999) 97:1–20.
  • •A simplified nomenclature for the many nuclear receptors.
  • ROBYR D, WOLFFE AP, WAHLI W: Nuclear hormone receptor coreg-ulators in action: diversity for shared tasks. Mol. Endocrinol (2000) 14:329–347.
  • •An exhaustive list of receptors and co-modulators.
  • GLASS CK, ROSENFELD MG: The coregulator exchange intranscriptional functions of nuclear receptors. Genes Dev. (2000) 1 4 :121–141.
  • •A good review of nuclear receptor co-regulators and how they work.
  • 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.
  • ZHOU G, CUMMINGS R, LI Y et al.: Nuclear receptors have distinct affinities for coactivators: characteriza-tion by fluorescence resonance energy transfer. Mol Endocrinol. (1998) 12:1594–1604.
  • •A good description of the FRET assay and its application to nuclear receptor recruitment of coactivator proteins.
  • SPIEGELMAN B, WU Z, PUGSERVER P: Control of adipogenesis and energy balance through PPARgamm a and novel co activators. Keystone Symposia on Nuclear Receptors. Taos, USA (2000) Abstract 012.
  • PARKS DJ, BLANCHARD SG, BLEDSOE RK et al.: Bile acids: natural ligands for an orphan nuclear receptor [see comments]. Science (1999) 284:1365–1368.
  • •This paper and two others [144, 145] describe the discovery that bile acids bind and activate FXR.
  • ISSEMAN I, GREEN S: Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature (1990) 347:645–650.
  • 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.
  • 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.
  • 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.
  • KLIEWER SA, FORMAN BM, BLUMBERG B et al.: Differen-tial expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc. Natl. Acad. Sci. USA (1994) 91:7355–7359.
  • 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.
  • MIYATA KS, MCCAW SE, PATEL HV, RACHUBINSKI RA, CAPONE JP: The orphan nuclear hormone receptor LICR alpha interacts with the peroxisome proliferator-activated receptor and inhibits peroxisome prolif-erator signaling. J Biol. Chem. (1996) 271:9189–9192.
  • BOGAZZI F, HUDSON LD, NIKODEM VM: Anovelhetero-dimerization partner for thyroid hormone receptor. Peroxisome proliferator-activated receptor. J. Biol. Chem. (1994) 269:11683–11686.
  • 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.
  • 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.
  • STAELS B, KOENIG W, HABIB A et al: Activation ofhuman aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators. Nature (1998) 393:790–793.
  • DELERIVE P, DE BOSSCHER K, BESNARD S et al.: Peroxi-some proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kapp aB and AP-1. j Biol. Chem. (1999) 274:32048–32054.
  • MUKHERJEE A et al: Abstracts of the Keystone Conference on PPARs. (1999) pp:30. Abstract 112.
  • LEE SS, PINEAU T, DRAGO J et al.: 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. (1995) 15:3012–3022.
  • 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.
  • KLIEWER SA, SUNDSETH SS, JONES SA et al: Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc. Nati Acad. Sci. USA (1997) 94:4318–4323.
  • BROWN PJ, WINEGAR DA, PLUNKET KD et al.: A ureido-thioisobutyric acid (GW9578) is a subtype-selective PPARalpha agonist with potent lipid-lowering activity. J. Med. Chem. (1999) 42:3785–3788.
  • •A good description of selective potent PPARa ligands.
  • WILLSON TM, BROWN PJ, STERNBACH DD, HENKE BR: The PPARs: from orphan receptors to drug discovery. J. Med. Chem. (2000) 43:527–550.
  • ••An excellent exhaustive review of the PPARs.
  • STAELS B, DALLONGEVILLE J, AUWERX J, SCHOONJANSK, LEITERSDORF E, FRUCHART JC: Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation (1998) 98:2088–2093.
  • RUBINS BLOOMFIELD H, ROBINS SJ et al: Gemfibrozilfor the secondary prevention of coronary heart disease in men with low levels of high-density lipopro-tein cholesterol. N Engl. J. Med. (1999) 341:410–418.
  • 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.
  • HENNUYER N, POULAIN P, MADSEN L et al.: Beneficialeffects of fibrates on apolipoprotein A-I metabolism occur independently of any peroxisome proliferative response. Circulation (1999) 99:2445–2451.
  • 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.
  • GUERRE-MILLO M, GERVOIS P, RASPE E et al.: Peroxi-some Proliferator-Activated Receptor a activators improve insulin sensitivity and reduce adiposity. J Biol. Chem. (2000) 275: 16638–16642.
  • BERGER J, LEIBOWITZ MD, DOEBBER TVV et al.: Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. j Biol. Chem. (1999) 274:6718–6725.
  • 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.
  • LEIBOWITZ A: Abstracts of the Keystone Symposia on thePPARs. (1999) pp25 Abstract 009.
  • 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.
  • HE TC, CHAN TA, VOGELSTEIN B, KINZLER KW: PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell (1999) 99:335–345.
  • 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.
  • FAJAS L, FRUCHART JC, AUWERX J: PPARgamm a3 m RNA: a distinct PPARgamma mRNA subtype transcribed from an independent promoter. FEBS Lett. (1998) 438:55–60.
  • 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.
  • SHIMOMURA I, HAMMER RE, RICHARDSON JA et al.: Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-lc in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev. (1998) 12:3182–3194.
  • MOITRA J, MASON MM, OLIVE M et al.: life without white fat: a transgenic mouse. Genes Dev. (1998)12:3168–3181.
  • TONTONOZ P, HU E, SPIEGELMAN BM: Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor [published erratum appears in Cell (1995) 80(6):following 957]. Cell (1994) 79:1147–1156.
  • ••First demonstration of the role of PPAR in adipogenesis.
  • NAGY L, TONTONOZ P, ALVAREZ JG, CHEN H, EVANSRM: Oxidized LDL reg-ulates macrophage gene expres-sion through ligand activation of PPARgamma. Cell (1998) 93:229–240.
  • KLIEWER SA, LENHARD JM, WILLSON TM, PATEL I, MORRIS DC, LEHMANN JM: A prostaglandin J2 metabo-lite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell (1995) 83:813–819.
  • 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.
  • MUKHERJEE R, DAVIES PJ, CROMBIE DL et al: Sensitiza-tion of diabetic and obese mice to insulin by retinoid X receptor agonists. Nature (1997) 386:407–410.
  • 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.
  • 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.
  • MURAKAMI K, TOBE K, IDE T et al.: A novel insulinsensitizer 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.
  • KUBOTA N, TERAUCHI Y, MIKI H et al.: PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mot. Cell (1999) 4:597–609.
  • ••First report of lowering insulin resistance by lowering PPARyactivity in heterozygous knockout mice.
  • BARAK Y, NELSON MC, ONG ES et al.: PPAR gamma is required for placental, cardiac and adipose tissue development. Mot. Cell (1999) 4:585–595.
  • 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.
  • DEEB SS, FAJAS L, NEMOTO M et al.: APro12Ala substitu-tion in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nature Genet. (1998) 20:284–287.
  • REGINATO MJ, BAILEY ST, KRAKOW SL et al.: A potent antidiabetic thiazolidinedione with unique p eroxi-some proliferator-activated receptor gamma-activating properties. J Biol. Chem. (1998) 273:32679–32684.
  • 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.
  • 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.
  • •All thiazolidiones are not the same and some function as partial agonists for PPARy.
  • 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.
  • 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.
  • 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.
  • 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.
  • •The crystal structure of PPARy with ligand and co-activator peptide.
  • 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.
  • GAMPE RT, MONTANA VG, LAMBERT MH, KLIEWER SA, WILLSON TM, XU HE: Asymmetry in the PPARy/RXRa crystal structure reveals the molecular basis of hetero-dimerization among nuclear receptors. Mot. Cell (2000) 5:545–555.
  • JIANG C, TING AT, SEED B: PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature (1998) 391:82–86.
  • 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.
  • RICOTE M, HUANG J, FAJAS L et al.: Expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) in human atherosclerosis and regula-tion in macrophages by colony stimulating factors and oxidized low density lipoprotein. Proc. Natl. Acad. Sci. USA (1998) 95:7614–7619.
  • 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.
  • DEMETRI GD, FLETCHER CD, MUELLER E et al.: Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglita-zone in patients with liposarcoma. Proc. Natl. Acad. Sci. USA (1999) 96:3951–3956.
  • 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.
  • ELSTNER E, MULLER C, KOSHIZUKA K et al: Iigands for peroxisome proliferator-activated receptor gamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc. Natl. Acad. Sci. USA (1998) 95:8806–8011.
  • 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.
  • SAEZ E, TONTONOZ P, NELSON MC et al.: Activators of the nuclear receptor PPARgamma enhance colon polyp formation. Nature Med. (1998) 4:1058–1061.
  • LEFEBVRE AM, CHEN I, DESREUMAUX P et al: Activation of the peroxisome proliferator-activated receptor gamma promotes the development of colon tumors in C5 7 BL/6J-APCMin /+ mice. Nature Med. (1998) 4:1053–1057.
  • SAMID D, SHACKS, SHERMAN LT: Phenylacetate: a novel nontoxic inducer of tumor cell differentiation. Cancer Res. (1992) 52:1988–1992.
  • SAMID D, WELLS M, GREENE ME, SHEN W, PALMER CNA, THIBAULT A: Peroxisome proliferator-activated receptor 7 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.
  • CHIANG JYL: Regulation of bile acid synthesis. Frontiers Biosci. (1998) 3:176–193.
  • 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 Biol. Chem. (1997) 272:18290–18297.
  • SHNEIDER BL: Expression cloning of the ileal sodium-dependent bile acid transporter. J. Pediatr. Gastroen-terol. Nutr. (1995) 20:233–235.
  • 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.
  • 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.
  • 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.
  • 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.
  • CHIANG JY, STROUP D: Identification and characteriza-tion of a putative bile acid-responsive element in cholesterol 7 alpha-hydroxylase gene promoter. J Biol. Chem. (1994) 269:17502–17507.
  • 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.
  • 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.
  • JANOWSKI BA, WILLY PJ, DEVI TR, FALCK JR, MANGELS-DORF DJ: An oxysterol signalling p athw ay mediated by the nuclear receptor LXR alpha. Nature (1996) 383:728–731.
  • •This was the first paper to announce the discovery that oxysterols are ligands for the previously orphan receptor LXR.
  • 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.
  • 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.
  • PEET DJ, TURLEY SD, MAW et al.: Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha. Cell (1998) 93:693–704.
  • ••This description of the mouse knockout of LXRademonstrates the role of LXR in stimulating bile acid metabolism through upregulation of cyp7a synthesis. The knockout mice develop fatty livers in response to a high cholesterol diet.
  • LUO Y, TALL AR: Sterol upreg-ulation of human CE1P expression in vitro and in transgenic mice by an LXR element. j Clin. Invest. (2000) 105:513–520.
  • HAYEK T, MASUCCI-MAGOULAS L, JIANG X et al.: Decreased early atherosclerotic lesions in hypertri-glyceridemic mice expressing cholesterol ester transfer protein transgene. J. Cli17. Invest. (1995) 96:2071–2071.
  • LALA DS, SYKA PM, LAZARCHIK SB, MANGELSDORF DJ, PARKER KL, HEYMAN RA: Activation of the orphan nuclear receptor steroidogenic factor 1 by oxysterols. Proc. Nati Acad. Sci. USA (1997) 94:4895–4900.
  • NITTA M, KU S, BROWN C, OKAMOTO AY, SHAN B: CPF: an orphan nuclear receptor that regulates liver-specific expression of the human cholesterol 7alpha-hydroxylase gene. Proc. Nati Acad. Sci. USA (1999) 96:6660–6665.
  • 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.
  • FORMAN BM, GOODE E, CHEN J et al.: Identification of a nuclear receptor that is activated by farnesol metabo-lites. Cell (1996) 81:687–693.
  • 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.
  • MAKISHIMA M, OKAMOTO AY, REPA JJ et al.: Identifica-tion of a nuclear receptor for bile acids. Science (1999) 284:1362–1365.
  • •This paper and two others [55, 145] describe the discovery that bile acids bind and activate FXR.
  • WANG H, CHEN J, HOLLISTER K, SOWERS LC, FORMAN BM: Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mot. Cell (1999) 3:543–553.
  • •This paper and two others [55, 144] describe the discovery that bile acids bind and activate FXR.
  • CHIANG JY, KIMMEL R, WEINBERGER C, STROUP D: Farnesoid X receptor responds to bile acids and represses cholesterol 7alpha-hydroxylase gene (CYP7 A1 ) transcription. J. Biol. Chem. (2000) 275:10918–10924.
  • 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.
  • SEOL W, CHUNG M, MOORE DD: Novel receptor interac-tion and repression domains in the orphan receptor SHP. Mot. Cell Biol. (1997) 17:7126–7131.
  • LEE YK, DELL H, DOWHAN DH, HADZOPOULOU-CLADARAS 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.
  • 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.
  • KANDA T, NIOT I, FOUCAUD L et al.: Effect of bile on the intestinal bile-acid binding protein (I-BABP) expres-sion. In vitro and in vivo studies. FEBS Lett. (1996) 384:131–134.
  • 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.
  • 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.
  • 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. Toxkol. Appl. Pharmacol. (1999) 1 5 4:76–83.
  • 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.
  • BURRIS TP, PELTON PD, ZHOU L, OSBORNE MC, CRYAN E, DEMAREST KT: A novel method for analysis of nuclear receptor function at natural promoters: peroxisome proliferator-activated receptor gamma agonist actions on aP2 gene expression detected using branched DNA messenger RNA quantitation. Mol. Endocrinol. (1999) 13:410–417.

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