Adipose targets for obesity drug development

Expert Opinion on Therapeutic Targets

Volumn 10, Issue 1, 2006, Pages 119-134

  Boss, Olivier ^a   Bergenhem, Nils ^a  

^a AdipoGenix   (United States)

Author keywords

3 adrenergic receptor ( 3 AR); 11 hydroxysteroid dehydrogenase type (11 HSD1); Acyl CoA:diacylglycerol acyltransferase (DGAT1); Acylation stimulating protein (ASP); Adiponectin; Insulin resistance; Leptin; Obesity; Oestrogen related receptor (ERR); Perilipin; Peroxisome proliferator activated receptor (PPAR); Protein tyrosine phosphatase 1B (PTP 1B); Stearoyl CoA desaturase 1 (SCD1)

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ACYL COENZYME A DESATURASE; ACYLATION STIMULATING PROTEIN; ADIPONECTIN; ANTISENSE OLIGONUCLEOTIDE; DIACYLGLYCEROL ACYLTRANSFERASE; FAMOXIN; FATTY ACID; FIBRIC ACID DERIVATIVE; GW 501516; HORMONE RECEPTOR STIMULATING AGENT; LEPTIN; LEPTIN RECEPTOR; LEPTIN RECEPTOR ANTAGONIST; MURAGLITAZAR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; PIOGLITAZONE; PROTEIN TYROSINE PHOSPHATASE 1B; PROTEIN TYROSINE PHOSPHATASE 1B INHIBITOR; PTP 3848; RECEPTOR BLOCKING AGENT; RECOMBINANT LEPTIN; ROSIGLITAZONE; TROGLITAZONE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ADIPOCYTE; ADIPOSE TISSUE; BODY WEIGHT; BODY WEIGHT DISORDER; CLINICAL TRIAL; CONGESTIVE HEART FAILURE; DRUG MEGADOSE; DRUG TARGETING; EDEMA; ENERGY METABOLISM; EPIDEMIC; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; HUMAN; NONHUMAN; OBESITY; PREVALENCE; PROTEIN EXPRESSION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; WEIGHT GAIN;

ADIPOSE TISSUE; ANIMALS; ANTI-OBESITY AGENTS; DRUG DELIVERY SYSTEMS; HUMANS; OBESITY; TECHNOLOGY, PHARMACEUTICAL;

EID: 33144469701     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728222.10.1.119     Document Type: Review

References (160)

1. NEEL JV: Diabetes mellitus: a 'thrifty' genotype rendered detrimental by 'progress'? Am. J. Hum. Genet. (1962) 14:353-362.
2. HAUNER H: Orlistat. In: Pharmacotherapy of Obesity. Options and Alternatives, Hofbauer KG, Keller U, Boss O (Eds.), CRC Press, Boca Raton, FL (2004):219-243.
3. RYAN DH: Sibutramine. In: Pharmacotherapy of Obesity: Options and Alternatives, Hofbauer KG, Keller U, Boss O (Eds.), CRC Press, Boca Raton, FL (2004):245-266.
4. WELLEN KE, HOTAMISLIGIL GS: Obesity-induced inflammatory changes in adipose tissue. J. Clin. Invest. (2003) 112(12):1785-1788.
5. HANSEN BC, BODKIN NL, ORTMEYER HK: Calorie restriction in nonhuman primates: mechanisms of reduced morbidity and mortality. Toxicol. Sci. (1999) 52(2 Suppl.):56-60.
6. BLANC S, SCHOELLER D, KEMNITZ J et al.: Energy expenditure of rhesus monkeys subjected to 11 years of dietary restriction. J. Clin. Endocrinol. Metab. (2003) 88(1):16-23.
7. POEHLMAN ET: Reduced metabolic rate after caloric restriction-can we agree on how to normalize the data? J. Clin. Endocrinol. Metab. (2003) 88(1):14-15.
8. DULLOO AG: A role for suppressed skeletal muscle thermogenesis in pathways from weight fluctuations to the insulin resistance syndrome. Acta Physiol. Scand. (2005) 184(4):295-307.
9. DULLOO AG, JACQUET J: An adipose-specific control of thermogenesis in body weight regulation. Int. J. Obes. Relat. Metab. Disord. (2001) 25(Suppl. 5):S22-S29.
10. RAVUSSIN E, KOZAK L: Energy Homeostasis. In: Pharmacotherapy of Obesity: Options and Alternatives, Hofbauer KG, Keller U, Boss O (Eds.), CRC Press, Boca Raton, FL (2004):3-23.
11. FAIN JN, MADAN AK, HILER ML, CHEEMA P, BAHOUTH SW: Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology (2004) 145(5):2273-2282.
12. HAUNER H: Secretory factors from human adipose tissue and their functional role. Proc. Nutr. Soc. (2005) 64(2):163-169.
13. SALTIEL AR: You are what you secrete. Nat. Med. (2001) 7(8):887-888.
14. RAJALA MW, SCHERER PE: Minireview: The adipocyte-at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology (2003) 144(9):3765-3773.
15. FARMER SR, AUWERX J: Adipose tissue: new therapeutic targets from molecular and genetic studies-IASO Stock Conference 2003 report. Obes. Rev. (2004) 5(4):189-196.
16. LAU DC, DHILLON B, YAN H, SZMITKO PE, VERMA S: Adipokines: molecular links between obesity and atheroslcerosis. Am. J. Physiol. Heart Circ. Physiol. (2005) 288(5):H2031-H2041.
17. MOLLER DE, KAUFMAN KD: Metabolic syndrome: a clinical and molecular perspective. Ann. Rev. Med. (2005) 56:45-62.
18. YANG Q, GRAHAM TE, MODY N et al.: Serum retinol binding protein 4 contributes to insulin resistance in obesity and Type 2 diabetes. Nature (2005) 436(7049):356-362.
19. LAFONTAN M: Fat cells: afferent and efferent messages define new approaches to treat obesity. Ann. Rev. Pharmacol. Toxicol. (2005) 45:119-146.
20. CHEN HC, RAO M, SAJAN MP et al.: Role of adipocyte-derived factors in enhancing insulin signaling in skeletal muscle and white adipose tissue of mice lacking acyl-CoA:diacylglycerol acyltransferase 1. Diabetes (2004) 53(6):1445-1451.
21. RABILLOUD T, KIEFFER S, PROCACCIO V et al.: Two-dimensional electrophoresis of human placental mitochondria and protein identification by mass spectrometry: toward a human mitochondrial proteome. Electrophoresis (1998) 19(6):1006-1014.
22. GYGI SP, RIST B, GERBER SA, TURECEK F, GELB MH, AEBERSOLD R: Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat. Biotechnol. (1999) 17(10):994-999.
23. MANN M, PANDEY A: Use of mass spectrometry-derived data to annotate nucleotidc and protein sequence databases. Trends Biochem. Sci. (2001) 26(1):54-61.
24. KRATCHMAROVA I, KALUME DE, BLAGOEV B et al.: A proteomic approach for identification of secreted proteins during the differentiation of 3T3-L1 preadipocytes to adipocytes. Mol. Cell Proteomics (2002) 1(3):213-222.
25. GIMENO RE, KLAMAN LD: Adipose tissue as an active endocrine organ-recent advances. Curr. Opin. Pharmacol. (2005) 5(2):122-128.
26. ZHANG Y, PROENCA R, MAFFEI M, BARONE M, LEOPOLD L, FRIEDMAN JM: Positional cloning of the mouse obese gene and its human homologue. Nature (1994) 372(6505):425-432.
27. HALAAS JL, GAJIWALA KS, MAFFEI M et al.: Weight-reducing effects of the plasma protein encoded by the obese gene. Science (1995) 269(5223):543-546.
28. PELLEYMOUNTER MA, CULLEN MJ, BAKER MB et al.: Effects of the obese gene product on body weight regulation in ob/ob mice. Science (1995) 269(5223):540-543.
29. FRIEDMAN JM, HALAAS JL: Leptin and the regulation of body weight in mammals. Nature (1998) 395(6704):763-770.
30. FAROOQI IS, MATARESE G, LORD GM et al.: Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J. Clin. Invest. (2002) 110(8):1093-1103.
31. HEYMSFIELD SB, GREENBERG AS, FUJIOKA K et al.: Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. J. Am. Med. Assoc. (1999) 282(16):1568-1575.
32. HUKSHORN CJ, SARIS WH, WESTERTERP-PLANTENGA MS, FARID AR, SMITH FJ, CAMPFIELD LA: Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB) administration in obese men. J. Clin. Endocrinol. Metab. (2000) 85(11):4003-4009.
33. KLEIN S, COPPACK SW, MOHAMED-ALI V, LANDT M: Adipose tissue leptin production and plasma leptin kinetics in humans. Diabetes (1996) 45(7):984-987.
34. CAMPFIELD LA, SMITH FJ: Leptin and other appetite suppressants. In: Pharmacotherapy of Obesity: Options and Alternatives, Hofbauer KG, Keller U, Boss O (Eds.), CRC Press, Boca Raton, FL (2004):321-344.
35. WANG ZW, PAN WT, LEE Y, KAKUMA T, ZHOU YT, UNGER RH: The role of leptin resistance in the lipid abnormalities of aging. FASEB J. (2001) 15(1):108-114.
36. CHENG A, UETANI N, SIMONCIC PD et al.: Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1B. Dev. Cell (2002) 2(4):497-503.
37. KASZUBSKA W, FALLS HD, SCHAEFER VG et al.: Protein tyrosine phosphatase 1B negatively regulates leptin signaling in a hypothalamic cell line. Mol. Cell. Endocrinol, (2002) 195(1-2):109-118.
38. ZABOLOTNY JM, BENCE-HANULEC KK, STRICKER-KRONGRAD A et al.: PTP1B regulates leptin signal transduction in vivo. Dev. Cell (2002) 2(4):489-495.
39. SCHERER PE, WILLIAMS S, FOGLIANO M, BALDINI G, LODISH HF: A novel serum protein similar to C1q, produced exclusively in adipocytes. J. Biol. Chem. (1995) 270(45):26746-26749.
40. HU E, LIANG P, SPIEGELMAN BM: AdipoQ is a novel adipose-specific gene dysregulated in obesity. J. Biol. Chem. (1996) 271(18):10697-10703.
41. MAEDA K, OKUBO K, SHIMOMURA I, FUNAHASHI T, MATSUZAWA Y, MATSUBARA K: cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (Adipose Most abundant Gene transcript 1). Biochem. Biophys. Res. Commun. (1996) 221(2):286-289.
42. PAJVANI UB, DU X, COMBS TP et al.: Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications for metabolic regulation and bioactivity. J. Biol. Chem. (2003) 278(11):9073-9085.
43. HAVEL PJ: Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes (2004) 53 (Suppl. 1):S143-S151.
44. BAJAJ M, SURAAMORNKUL S, PIPER P et al.: Decreased plasma adiponectin concentrations are closely related to hepatic fat content and hepatic insulin resistance in pioglitazone-treated Type 2 diabetic patients. J. Clin. Endocrinol. Metab. (2004) 89(1):200-206.
45. MIYAZAKI Y, MAHANKALI A, WAJCBERG E, BAJAJ M, MANDARINO LJ, DEFRONZO RA. Effect of pioglitazone on circulating adipocytokine levels and insulin sensitivity in Type 2 diabetic patients. J. Clin. Endocrinol. Metab. (2004) 89(9):4312-4319.
46. BOUSKILA M, PAJVANI UB, SCHERER PE: Adiponectin: a relevant player in PPARgamma-agonist-mediated improvements in hepatic insulin sensitivity? Int. J. Obes. (2005) 29(Suppl. 1):S17-S23.
47. KADOWAKI T, YAMAUCHI T: Adiponectin and adiponectin receptors. Endocr. Rev. (2005) 26(3):439-451.
48. MAEDA N, SHIMOMURA I, KISHIDA K et al.: Diet-induced insulin resistance in mice lacking adiponectin/ ACRP30. Nat. Med (2002) 8(7):731-737.
49. MA K, CABRERO A, SAHA PK et al.: increased beta -oxidation but no insulin resistance or glucose intolerance in mice lacking adiponectin. J. Biol. Chem. (2002) 277(38):34658-34661.
50. BERG AH, COMBS TP, DU X, BROWNLEE M, SCHERER PE: The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat. Med. (2001) 7(8):947-953.
51. COMBS TP, BERG AH, OBICI S, SCHERER PE, ROSSETTI L: Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. J. Clin. Invest. (2001) 108(12):1875-1881.
52. FRUEBIS J, TSAO TS, JAVORSCHI S et al.: Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc. Natl. Acad Sci. USA (2001) 98(4):2005-2010.
53. HEILBRONN LK, SMITH SR, RAVUSSIN E: The insulin-sensitizing role of the fat derived hormone adiponectin. Curr. Pharm. Des. (2003) 9(17):1411-1418.
54. YAMAUCHI T, KAMON J, ITO Y et al.: Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature (2063) 423(6941):762-769.
55. HUG C, WANG J, AHMAD NS, BOGAN JS, TSAO TS, LODISH HF: T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/ adiponectin. Proc. Natl. Acad. Sci. USA (2004) 101(28):10308-10313.
56. YASRUEL Z, CIANFLONE K, SNIDERMAN AD, ROSENBLOOM M, WALSH M, RODRIGUEZ MA: Effect of acylation stimulating protein on the triacylglycerol synthetic pathway of human adipose tissue. Lipids (1991) 26(7):495-499.
57. FARAJ M, CIANFLONE K: Differential regulation of fatty acid trapping in mouse adipose tissue and muscle by ASP. Am. J. Physiol. Endocrinol. Metab. (2004) 287(1):E150-E159.
58. MURRAY I, SNIDERMAN AD, HAVEL PJ, CIANFLONE K: Acylation stimulating protein (ASP) deficiency alters postprandial and adipose tissue metabolism in male mice. J. Biol. Chem. (1999) 274(51):36219-36225,
59. MURRAY I, HAVEL PJ, SNIDERMAN AD, CIANFLONE K: Reduced body weight, adipose tissue, and leptin levels despite increased energy intake in female mice lacking acylation-stimulating protein. Endocrinology (2000) 141(3):1041-1049.
60. XIA Z, STANHOPE KL, DIGITALE E et al.: Acylation-stimulating protein (ASP)/ complement C3adesArg deficiency results in increased energy expenditure in mice. J. Biol. Chem. (2004) 279(6):4051-4057.
61. CAIN SA, MONK PN: The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74). J. Biol. Chem. (2002) 277(9):7165-7169.
62. KALANT D, CAIN SA, MASLOWSKA M, SNIDERMAN AD, CIANFLONE K, MONK PN: The chemoattractant receptor-like protein C5L2 binds the C3a des-Arg77/acylation-stimulating protein. J. Biol. Chem. (2003) 278(13):11123-11129.
63. CIANFLONE K: Acylation stimulating protein and triacylglycerol synthesis: potential drug targets? Curr. Pharm. Des. (2003) 9(17):1397-1410.
64. MEIJSSEN S, VAN DIJK H, VERSEYDEN C, ERKELENS DW, CABEZAS MC: Delayed and exaggerated postprandial complement component 3 response in familial combined hyperlipidemia. Arterioscler. Thromb. Vasc. Biol. (2002) 22(5):811-816.
65. LAZAR MA: PPAR gamma, 10 years later. Biochimie (2005) 87(1):9-13.
66. YAMAUCHI T, WAKI H, KAMON J et al.: Inhibition of RXR and PPARgamma ameliorates diet-induced obesity and Type 2 diabetes. J. Clin. Invest. (2001) 108(7):1001-1013.
67. EVANS RM, BARISH GD, WANG YX: PPARs and the complex journey to obesity. Nat. Med. (2004) 10(4):355-361.
68. BERGER JP, PETRO AF, MACNAUL KL et al.: Distinct properties and advantages of a novel peroxisome proliferator-activated protein [gamma] selective modulator. Mol. Endocrinol. (2003) 17(4):662-676.
69. ARGMANN CA, COCK TA, AUWERX J: Peroxisome proliferator-activated receptor gamma: the more the merrier? Eur. J. Clin. Invest. (2005) 35(2):82-92; discussion 80.
70. SMITH SR: Metabolic syndrome targets. Curr. Drug Targets CNS Neurol. Disord. (2004) 3(5):431-439.
71. BERGER JP, AKIYAMA TE, MEINKE PT: PPARs: therapeutic targets for metabolic disease. Trends Pharmacol. Sci. (2005) 26(5):244-251.
72. KUBOTA N, TERAUCHI Y, MIKI H et al.: PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol. Cell (1999) 4(4):597-609.
73. MILES PD, BARAK Y, HE W, EVANS RM, OLEFSKY JM: Improved insulin-sensitivity in mice heterozygous for PPAR-gamma dcficiency. J. Clin. Invest. (2000) 105(3):287-292.
74. YAMAUCHI T, KAMON J, WAKI H et al.: The mechanisms by which both heterozygous peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin resistance. J. Biol. Chem. (2001) 276(44):41245-41254.
75. RIEUSSET J, TOURI F, MICHALIK L et al.: A new selective peroxisome proliferator-activated receptor gamma antagonist with antiobesity and antidiabetic activity. Mol. Endocrinol. (2002) 16(11):2628-2644.
76. CROWLEY VEF, VIDAL-PUIG AJ: Peripheral Targets for Antiobesity Drugs. In: Pharmacotherapy of Obesity: Options and Alternatives, Hofbauer KG, Keller U, Boss O (Eds.), CRC Press, Boca Raton, FL (2004):345-362.
77. LUQUET S, LOPEZ-SORIANO J, HOLST D et al.: Roles of peroxisome proliferator-activated receptor delta (PPARdelta) in the control of fatty acid catabolism. A new target for the treatment of metabolic syndrome. Biochimie (2004) 86(11):833-837.
78. GRIMALDI PA: Regulatory role of peroxisome proliferator-activated receptor delta (PPAR delta) in muscle metabolism. A new target for metabolic syndrome treatment? Biochimie (2005) 87(1):5-8.
79. 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):2299-2301.
80. WANG YX, ZHANG CL, YU RT et al.: Regulation of muscle fiber type and running endurance by PPARdelta. PLoS Biol. (2004) 2(10):e294.
81. 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.
82. 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):15924-5929.
83. MARCY TR, BRITTON ML, BLEVINS SM: Second-generation thiazolidinediones and hepatotoxicity. Ann. Pharmacother. (2004) 38(9):1419-1423.
84. MIYAZAKI M, KIM YC, GRAY-KELLER MP, ATTIE AD, NTAMBI JM: The biosynthesis of hepatic cholesterol esters and triglycerides is impaired in mice with a disruption of the gene for stearoyl-CoA desaturase 1. J. Biol. Chem. (2000) 275(39):30132-30138.
85. MIYAZAKI M, MAN WC, NTAMBI JM: Targeted disruption of stearoyl-CoA desaturase1 gene in mice causes atrophy of sebaceous and meibomian glands and depletion of wax esters in the eyelid. J. Nutr. (2001) 131(9):2260-2268.
86. JIANG G, LI Z, LIU F et al.: Prevention of obesity in mice by antisense oligonucleotide inhibitors of stearoyl-CoA desaturase-1. J. Clin. Invest. (2005) 115(4):1030-1038.
87. COHEN P, MIYAZAKI M, SOCCI ND et al.: Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science (2002) 297(5579):240-243.
88. COHEN P, NTAMBI JM, FRIEDMAN JM: Stearoyl-CoA desaturase-1 and the metabolic syndrome. Curr. Drug Targets Immune Endocr. Metabol. Disord. (2003) 3(4):271-280.
89. COHEN P, FRIEDMAN JM: Leptin and the control of metabolism: role for stearoyl-CoA desaturase-1 (SCD-1). J. Nutr. (2004) 134(9):2455S-2463S.
90. CHEN HC, FARESE RV, Jr.: Inhibition of triglyceride synthesis as a treatment strategy for obesity lessons from DGAT1-deficient mice. Arterioscler. Thromb. Vasc. Biol. (2005) 25(3):482-486.
91. SMITH SJ, CASES S, JENSEN DR et al.: Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat. Genet. (2000) 25(1):87-90.
92. CHEN HC, SMITH SJ, LADHA Z et al.: Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1. J. Clin. Invest. (2002) 109(8):1049-1055.
93. CHEN HC, JENSEN DR, MYERS HM, ECKEL RH, FARESE RV, Jr.: Obesity resistance and enhanced glucose metabolism in mice transplanted with white adipose tissue lacking acyl CoA:diacylglycerol acyltransferase 1. J. Clin. Invest. (2003) 111(11):1715-1722.
94. GOLDSTEIN BJ: Protein-tyrosine phosphatase 1B (PTP1B): a novel therapeutic target for Type 2 diabetes mellitus, obesity and related states of insulin resistance. Curr. Drug Targets Immune Endocr. Metabol. Disord (2001) 1(3):265-275.
95. JOHNSON TO, ERMOLIEFF J, JIROUSEK MR: Protein tyrosine phosphatase 1B inhibitors for diabetes. Nat. Rev. Drug Discov. (2002) 1(9):696-709.
96. ELCHEBLY M, PAYETTE P, MICHALISZYN E et al.: Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science (1999) 283(5407):1544-1548.
97. KLAMAN LD, BOSS O, PERONI OD et al.: Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice. Mol. Cell. Biol. (2000) 20(15):5479-5489.
98. RONDINONE CM, TREVILLYAN JM, CLAMPIT J et al.: Protein tyrosine phosphatase 1B reduction regulates adiposity and expression of genes involved in lipogenesis. Diabetes (2002) 51(8):2405-2411.
99. ZINKER BA, RONDINONE CM, TREVILLYAN JM et al.: PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice. Proc. Natl. Acad. Sci. USA (2002) 99(17):11357-11362.
100. GUM RJ, GAEDE LL, KOTERSKI SL et al.: Reduction of protein tyrosine phosphatase 1B increases insulin-dependent signaling in ob/ob mice. Diabetes (2003) 52(1):21-28.
101. WARING JF, CIURLIONIS R, CLAMPIT JE et al.: PTP1B antisense-trcated mice show regulation of genes involved in lipogenesis in liver and fat. Mol. Cell. Endocrinol. (2003) 203(1-2):155-168.
102. SUZUKI T, HIROKI A, WATANABE T, YAMASHITA T, TAKEI I, UMEZAWA K: Potentiation of insulin-related signal transduction by a novel protein-tyrosine phosphatase inhibitor, Et-3,4-dephostatin, on cultured 3T3-L1 adipocytes. J. Biol. Chem. (2001) 276(29):27511-27518.
103. GUERTIN KR, SETTI L, QI L et al.: Identification of a novel class of orally active pyrimido [5,4-3][1,2,4] triazine-5,7-diamine-based hypoglycemic agents with protein tyrosine phosphatase inhibitory activity. Bioorg. Med. Chem. Lett. (2003) 13(17):2895-2898.
104. LIU G, SZCZEPANKIEWICZ BG, PEI Z et al.: Discovery and structure-activity relationship of oxalylarylaminobenzoic acids as inhibitors of protein tyrosine phosphatase 1B. J. Med. Chem. (2003) 46(11):2093-2103.
105. UMEZAWA K, KAWAKAMI M, WATANABE T. Molecular design and biological activities of protein-tyrosine phosphatase inhibitors. Pharmacol. Ther. (2003) 99(1):15-24.
106. CHEON HG, KIM SM, YANG SD, HA JD, CHOI JK: Discovery of a novel protein tyrosine phosphatase-1B inhibitor, KR61639: potential development as an antihyperglycemic agent. Eur. J. Pharmacol. (2004) 485(1-3):333-339.
107. DEAN D, ORLOWSKI L, COVERDALE S, WHITEHOUSE D, FAN C, BALKAN B: Chronic treatment with IDD-3, a Novel PTP1b inhibitor, results in sustained improvements in glucose homeostasis in ob/ob and db/db mice. Diabetes (2004) 53(Suppl. 2):516-P.
108. FAN C, DEAN D, WHITEHOUSE DL, COVERDALE S, BALKAN B: The protein tyrosine phosphase-1B (PTP1B) inhibitor, IDD-3, acutely improves glucose homeostasis in ob/ob mice and insulin action in the euglycemic-hyperinsulinemic clamp in high fat fed rats. Diabetes (2004) 53(Suppl. 2):650-P.
109. BALKAN B, BEELER S, FAN C, ORLOWSKI L, WHITEHOUSE D, DEAN DJ: Pharmacological inhibition of PTP1B prevents development of diet-induced obesity and insulin resistance. Diabetes (2004) 53(Suppl. 2):618-P.
110. GRANNEMAN JG: Why do adipocytes make the beta 3 adrenergic receptor? Cell Signal. (1995) 7(1):9-15.
111. DENG C, PAOLONI-GIACOBINO A, KUEHNE F et al.: Respective degree of expression of beta 1-, beta 2- and beta 3-adrenoceptors in human brown and white adipose tissues. Br. J. Pharmacol. (1996) 118(4):929-934.
112. GRANNEMAN JG, LI P, ZHU Z, LU Y: Metabolic and cellular plasticity in white adipose tissue I: effects of beta3-adrenergic receptor activation. Am. J. Physiol. Endocrinol. Metab. (2005) 289(4):E608-E616.
113. LARSEN TM, TOUBRO S, VAN BAAK MA et al.: Effect of a 28-d treatment with L-796568, a novel beta(3)-adrenergic receptor agonist, on energy expenditure and body composition in obese men. Am. J. Clin. Nutr. (2002) 76(4):780-788.
114. HARPER M-E, DENT R, TESSON F, MCPHERSON R: Targeting Thermogenesis in the Development of Antiobesity Drugs. In: Pharmacotherapy of Obesity: Options and Alternatives, Hofbauer KG, Keller U, Boss O (Eds.), CRC Press, Boca Raton, FL (2004):363-383.
115. COLLINS S, CAO W, ROBIDOUX J: Learning new tricks from old dogs: beta-adrenergic receptors teach new lessons on firing up adipose tissue metabolism. Mol. Endocrinol. (2004) 18(9):2123-2131.
116. MORTON NM, PATERSON JM, MASUZAKI H et al: Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11 beta-hydroxysteroid dehydrogenase Type 1-deficient mice. Diabetes (2004) 53(4):931-938.
117. MASUZAKI H, PATERSON J, SHINYAMA H et al.: A transgenic model of visceral obesity and the metabolic syndrome. Science (2001) 294(5549):2166-2170.
118. KANNISTO K, PIETILAINEN KH, EHRENBORG E et al.: Overexpression of 11beta-hydroxysteroid dehydrogenase-1 in adipose tissue is associated with acquired obesity and features of insulin resistance: studies in young adult monozygotic twins. J. Clin. Endocrinol. Metab. (2004) 89(9):4414-4421.
119. MASUZAKI H, FLIER JS: Tissue-specific glucocorticoid reactivating enzyme, 11 beta-hydroxysteroid dehydrogenase Type 1 (11 beta-HSD1)-a promising drug target for the treatment of metabolic syndrome. Curr. Drug Targets Immune Endocr. Metabol. Disord. (2003) 3(4):255-262.
120. SOUZA SC, DE VARGAS LM, YAMAMOTO MT et al.: Overexpression of perilipin A and B blocks the ability of tumor necrosis factor alpha to increase lipolysis in 3T3-L1 adipocytes. J. Biol. Chem. (1998) 273(38):24665-24669.
121. SOUZA SC, MULIRO KV, LISCUM L et al.: Modulation of hormone-sensitive lipase and protein kinase A-mediated lipolysis by perilipin A in an adenoviral reconstituted system. J. Biol. Chem. (2002) 277(10):8267-8272.
122. TANSEY JT, SZTALRYD C, GRUIA-GRAY J et al.: Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity. Proc. Natl. Acad. Sci. USA (2001) 98(11):6494-6499.
123. SAHA PK, KOJIMA H, MARTINEZ-BOTAS J, SUNERAG AL, CHAN L: Metabolic adaptations in the absence of perilipin: increased beta-oxidation and decreased hepatic glucose production associated with peripheral insulin resistance but normal glucose tolerance in perilipin-null mice. J. Biol. Chem. (2004) 279(34):35150-35158.
124. GROVER GJ, MELLSTROM K, YE L et al.: Selective thyroid hormone receptor-beta activation: a strategy for reduction of weight, cholesterol, and lipoprotein (a) with reduced cardiovascular liability. Proc. Natl. Acad. Sci. USA (2003) 100(17):10067-10072.
125. GROVER GJ, MELLSTROM K, MALM J: Development of the thyroid hormone receptor beta-subtype agonist KB-141: a strategy for body weight reduction and lipid lowering with minimal cardiac side effects. Cardiovasc. Drug Rev. (2005) 23(2):133-148.
126. LAZAR MA: A sweetheart deal for thyroid hormone. Endocrinology (2000) 141(9):3055-3056.
127. AREND WP: Interleukin 1 receptor antagonist. A new member of the interleukin 1 family. J. Clin. Invest. (1991) 88(5):1445-1451.
128. MATSUKI T, HORAI R, SUDO K, IWAKURA Y: IL-1 plays an important role in lipid metabolism by regulating insulin levels under physiological conditions. J. Exp. Med. (2003) 198(6):877-888.
129. SOMM E, HENRICHOT E, PERNIN A et al.: Decreased fat mass in interleukin-1 receptor antagonist deficient mice: impact on adipogenesis, food intake and energy expenditure. Diabetes (2005) 54:3503-3509.
130. HORAI R, SAIJO S, TANIOKA H et al.: Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice. J. Exp. Med. (2000) 191(2):313-320.
131. HIMMS-HAGEN J, MELNYK A, ZINGARETTI MC, CERESI E, BARBATELLI G, CINTI S: Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes. Am. J. Physiol. Cell Physiol. (2000) 279(3):C670-C681.
132. GRANNEMAN JG, BURNAZI M, ZHU Z, SCHWAMB LA: White adipose tissue contributes to UCP1-independent thermogenesis. Am. J. Physiol. Endocrinol. Metab. (2003) 285(6):E1230-E1236.
133. HIMMS-HAGEN J: Exercise in a pill: feasibility of energy expenditure targets. Curr. Drug Targets CNS Neurol. Disord. (2004) 3(5):389-409.
134. ROSSMEISL M, FLACHS P, BRAUNER P et al.: Role of energy charge and AMP-activated protein kinase in adipocytes in the control of body fat stores. Int. J. Obes. Relat. Metab. Disord. (2004) 28(Suppl. 4):S38-S44.
135. GUERRA C, KOZA RA, YAMASHITA H, WALSH K, KOZAK LP: Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. J. Clin. Invest. (1998) 102(2):412-420.
136. ROBIDOUX J, MARTIN TL, COLLINS S: Beta-adrenergic receptors and regulation of energy expenditure: a family affair. Ann. Rev. Pharmacol. Toxicol. (2004) 44:297-323.
137. WU Z, PUIGSERVER P, ANDERSSON U et al.: Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell(1999) 98(1):115-124.
138. SPIEGELMAN BM, PUIGSERVER P, WU Z: Regulation of adipogenesis and energy balance by PPARgamma and PGC-1. Int. J. Obes. Relat. Metab. Disord. (2000) 24(Suppl. 4):S8-S10.
139. LIN J, WU H, TARR PT et al.: Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature (2002) 418(6899):797-801.
140. KAMEI Y, OHIZUMI H, FUJITANI Y et al.: PPARgamma coactivator 1beta/ERR ligand 1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity. Proc. Natl. Acad. Sci. USA (2003) 100(21):12378-12383.
141. MEIRHAEGHE A, CROWLEY V, LENAGHAN C et al.: Characterization of the human, mouse and rat PGC1 beta (peroxisome-proliferator-activated receptor-gamma co-activator 1 beta) gene in vitro and in vivo. Biochem J. (2003) 373(Pt 1):155-165.
142. ST-PIERRE J, LIN J, KRAUSS S et al.: Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells. J. Biol. Chem. (2003) 278(29):26597-25603.
143. LIN J, HANDSCHIN C, SPIEGELMAN BM: Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab. (2005) 1(6):361-370.
144. YOON JC, PUIGSERVER P, CHEN G et al.: Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature (2001) 413(6852):131-138.
145. KNUTTI D, KRESSLER D, KRALLI A: Regulation of the transcriptional coactivator PGC-1 via MAPK-sensitive interaction with a repressor. Proc. Natl. Acad. Sci. USA (2001) 98(17):9713-9718.
146. FAN M, RHEE J, ST-PIERRE J et al.: Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1alpha: modulation by p38 MAPK. Genes Dev. (2004) 18(3):278-289.
147. SCHREIBER SN, KNUTTI D, BROGLI K, UHLMANN T, KRALLI A: The transcriptional coactivator PGC-1 regulates the expression and activity of the orphan nuclear receptor estrogen-related receptor alpha (ERRalpha). J. Biol. Chem. (2003) 278(11):9013-9018.
148. MOOTHA VK, HANDSCHIN C, ARLOW D et al.: Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle. Proc. Natl. Acad. Sci. USA (2004) 101(17):6570-6575.
149. SCHREIBER SN, EMTER R, HOCK MB et al.: The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis. Proc. Natl. Acad. Sci. USA (2004) 101(17):6472-6477.
150. WILLY PJ, MURRAY IR, QIAN J et al.: Regulation of PPARgamma coactivator 1alpha (PGC-1alpha) signaling by an estrogen-related receptor alpha (ERRalpha) ligand. Proc. Natl. Acad. Sci. USA (2004) 101(24):8912-8917.
151. KALLEN J, SCHLAEPPI JM, BITSCH F et al.: Evidence for ligand-independent transcriptional activation of the human estrogen-related receptor alpha (ERRalpha): crystal structure of ERRalpha ligand binding domain in complex with peroxisome proliferator-activated receptor coactivator-1alpha. J. Biol. Chem. (2004) 279(47):49330-49337.
152. SCHULMAN IG, HEYMAN RA. The flip side: Identifying small molecule regulators of nuclear receptors. Chem. Biol. (2004) 11(5):639-646.
153. LANGIN D, LUCAS S, LAFONTAN M: Millennium fat-cell lipolysis reveals unsuspected novel tracks. Horm. Metab. Res. (2000) 32(11-12):443-452.
154. LI P, ZHU Z, LU Y, GRANNEMAN JG: Metabolic and cellular plasticity in white adipose tissue II: role of peroxisome proliferator-activated receptor-alpha. Am. J. Physiol. Endocrinol. Metab. (2005) 289(4):E617-E626.
155. XUE B, COULTER A, RIM JS, KOZA RA, KOZAK LP: Transcriptional synergy and the regulation of Ucp1 during brown adipocyte induction in white fat depots. Mol. Cell. Biol. (2005) 25(18):8311-8322.
156. BODKIN NL, PILL J, MEYER K, HANSEN BC: The effects of K-111, a new insulin-sensitizer, on metabolic syndrome in obese prediabetic rhesus monkeys. Horm. Metab. Res. (2003) 35(10):617-624.
157. SCHAFER SA, HANSEN BC, VOLKL A, FAHIMI HD, PILL J: Biochemical and morphological effects of K-111, a peroxisome proliferator-activated receptor (PPAR)alpha activator, in non-human primates. Biochem. Pharmacol. (2004) 68(2):239-251.
158. RABEN DM, BALDASSARE JJ: A new lipase in regulating lipid mobilization: hormone-sensitive lipase is not alone. Trends Endocrinol. Metab. (2005) 16(2):35-36.
159. ZECHNER R, STRAUSS JG, HAEMMERLE G, LASS A, ZIMMERMANN R: Lipolysis: pathway under construction. Curr. Opin. Lipidol. (2005) 16(3):333-340.
160. MCFEE RB, CARACCIO TR, MCGUIGAN MA, REYNOLDS SA, BELLANGER P: Dying to be thin: a dinitrophenol related fatality. Vet. Hum. Toxicol. (2004) 46(5):251-254.