Small-Molecule Compounds that Modulate Lipolysis in Adipose Tissue: Targeting Strategies and Molecular Classes

Chemistry and Biology

Volumn 13, Issue 10, 2006, Pages 1019-1027

  Wang, Minghan ^a   Fotsch, Christopher ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG DERIVATIVE; INSULIN; NICOTINIC ACID;

ADIPOSE TISSUE; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECT; HUMAN; LIPOLYSIS; METABOLISM; MOLECULAR WEIGHT; REVIEW;

ADIPOSE TISSUE; ANIMALS; HUMANS; INSULIN; LIPOLYSIS; MOLECULAR STRUCTURE; MOLECULAR WEIGHT; NIACIN;

EID: 33749671772     PISSN: 10745521     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.chembiol.2006.09.010     Document Type: Review

References (122)

1. Reaven G.M., Hollenbeck C., Jeng C.Y., Wu M.S., and Chen Y.D. Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM. Diabetes 37 (1988) 1020-1024
2. Pankow J.S., Duncan B.B., Schmidt M.I., Ballantyne C.M., Couper D.J., Hoogeveen R.C., and Golden S.H. Atherosclerosis Risk in Communities Study. Fasting plasma free fatty acids and risk of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes Care 27 (2004) 77-82
3. Paolisso G., Tataranni P.A., Foley J.E., Bogardus C., Howard B.V., and Ravussin E. A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM. Diabetologia 38 (1995) 1213-1217
4. Havel R.J. Conversion of plasma free fatty acids into triglycerides of plasma lipoprotein fractions in man. Metabolism 10 (1961) 1031-1036
5. Ferrannini E., Barrett E.J., Bevilacqua S., and DeFronzo R.A. Effect of fatty acids on glucose production and utilization in man. J. Clin. Invest. 72 (1983) 1737-1747
6. Iozzo P., Lautamaki R., Geisler F., Virtanen K.A., Oikonen V., Haaparanta M., Yki-Jarvinen H., Ferrannini E., Knuuti J., and Nuutila P. Non-esterified fatty acids impair insulin-mediated glucose uptake and disposition in the liver. Diabetologia 47 (2004) 1149-1156
7. Chen X., Iqbal N., and Boden G. The effects of free fatty acids on gluconeogenesis and glycogenolysis in normal subjects. J. Clin. Invest. 103 (1999) 365-372
8. Roden M., Krssak M., Stingl H., Gruber S., Hofer A., Furnsinn C., Moser E., and Waldhausl W. Rapid impairment of skeletal muscle glucose transport/phosphorylation by free fatty acids in humans. Diabetes 48 (1999) 358-364
9. Homko C.J., Cheung P., and Boden G. Effects of free fatty acids on glucose uptake and utilization in healthy women. Diabetes 52 (2003) 487-491
10. de Jongh R.T., Serne E.H., Ijzerman R.G., de Vries G., and Stehouwer C.D. Free fatty acid levels modulate microvascular function: relevance for obesity-associated insulin resistance, hypertension, and microangiopathy. Diabetes 53 (2004) 2873-2882
11. Dubois M., Kerr-Conte J., Gmyr V., Bouckenooghe T., Muharram G., D'Herbomez M., Martin-Ponthieu A., Vantyghem M.C., Vandewalle B., and Pattou F. Non-esterified fatty acids are deleterious for human pancreatic islet function at physiological glucose concentration. Diabetologia 47 (2004) 463-469
12. Boden G., and Shulman G.I. Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and beta-cell dysfunction. Eur. J. Clin. Invest. 32 Suppl. 3 (2002) 14-23
13. Yeaman S.J. Hormone-sensitive lipase-new roles for an old enzyme. Biochem. J. 379 (2000) 11-22
14. Kershaw E.E., Hamm J.K., Verhagen L.A., Peroni O., Katic M., and Flier J.S. Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrin. Diabetes 55 (2006) 148-157
15. Zimmermann R., Strauss J.G., Haemmerle G., Schoiswohl G., Birner-Gruenberger R., Riederer M., Lass A., Neuberger G., Eisenhaber F., Hermetter A., et al. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 306 (2004) 1383-1386
16. Villena J.A., Roy S., Sarkadi-Nagy E., Kim K.H., and Sul H.S. Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. J. Biol. Chem. 279 (2004) 47066-47075
17. 2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. J. Biol. Chem. 279 (2004) 48968-48975
18. Hales C.N., Luzio J.P., and Siddle K. Hormonal control of adipose-tissue lipolysis. Biochem. Soc. Symp. 43 (1978) 97-135
19. Skowronski R., Hollenbeck C.B., Varasteh B.B., Chen Y.D., and Reaven G.M. Regulation of non-esterified fatty acid and glycerol concentration by insulin in normal individuals and patients with type 2 diabetes. Diabet. Med. 8 (1991) 330-333
20. Campbell P.J., Carlson M.G., and Nurjhan N. Fat metabolism in human obesity. Am. J. Physiol. 266 (1994) E600-E605
21. Nurjhan N., Consoli A., and Gerich J. Increased lipolysis and its consequences on gluconeogenesis in non-insulin-dependent diabetes mellitus. J. Clin. Invest. 89 (1992) 169-175
22. Carlson L.A. Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review. J. Intern. Med. 258 (2005) 94-114
23. Bajaj M., Suraamornkul S., Kashyap S., Cusi K., Mandarino L., and DeFronzo R.A. Sustained reduction in plasma free fatty acid concentration improves insulin action without altering plasma adipocytokine levels in subjects with strong family history of type 2 diabetes. J. Clin. Endocrinol. Metab. 89 (2004) 4649-4655
24. Vaag A., Skott P., Damsbo P., Gall M.A., Richter E.A., and Beck-Nielsen H. Effect of the antilipolytic nicotinic acid analogue acipimox on whole-body and skeletal muscle glucose metabolism in patients with non-insulin-dependent diabetes mellitus. J. Clin. Invest. 88 (1991) 1282-1290
25. Boden G., Chen X., and Iqbal N. Acute lowering of plasma fatty acids lowers basal insulin secretion in diabetic and nondiabetic subjects. Diabetes 47 (1998) 1609-1612
26. Santomauro A.T., Boden G., Silva M.E., Rocha D.M., Santos R.F., Ursich M.J., Strassmann P.G., and Wajchenberg B.L. Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects. Diabetes 48 (1999) 1836-1841
27. Stern R.H., Spence J.D., Freeman D.J., and Parbtani A. Tolerance to nicotinic acid flushing. Clin. Pharmacol. Ther. 50 (1991) 66-70
28. 2 release following oral administration of niacin in humans. J. Invest. Dermatol. 98 (1992) 812-815
29. Dalton T.A., and Berry R.S. Hepatotoxicity associated with sustained-release niacin. Am. J. Med. 93 (1992) 102-104
30. Kahn S.E., Beard J.C., Schwartz M.W., Ward W.K., Ding H.L., Bergman R.N., Taborsky Jr. G.J., and Porte Jr. D. Increased beta-cell secretory capacity as mechanism for islet adaptation to nicotinic acid-induced insulin resistance. Diabetes 38 (1989) 562-568
31. Garg A., and Grundy S.M. Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus. JAMA 264 (1990) 723-726
32. Soni K.G., Lehner R., Metalnikov P., O'Donnell P., Semache M., Gao W., Ashman K., Pshezhetsky A.V., and Mitchell G.A. Carboxylesterase 3 (EC 3.1.1.1) is a major adipocyte lipase. J. Biol. Chem. 279 (2004) 40683-40689
33. Schoenborn V., Heid I.M., Vollmert C., Lingenhel A., Adams T.D., Hopkins P.N., Illig T., Zimmermann R., Zechner R., Hunt S.C., et al. The ATGL gene is associated with free fatty acids, triglycerides, and type 2 diabetes. Diabetes 55 (2006) 1270-1275
34. Osuga J., Ishibashi S., Oka T., Yagyu H., Tozawa R., Fujimoto A., Shionoiri F., Yahagi N., Kraemer F.B., Tsutsumi O., et al. Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity. Proc. Natl. Acad. Sci. USA 97 (2000) 787-792
35. Wang S.P., Laurin N., Himms-Hagen J., Rudnicki M.A., Levy E., Robert M.F., Pan L., Oligny L., and Mitchell G.A. The adipose tissue phenotype of hormone-sensitive lipase deficiency in mice. Obes. Res. 9 (2001) 119-128
36. Haemmerle G., Zimmermann R., Hayn M., Theussl C., Waeg G., Wagner E., Sattler W., Magin T.M., Wagner E.F., and Zechner R. Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J. Biol. Chem. 277 (2002) 4806-4815
37. Sztalryd C., Xu G., Dorward H., Tansey J.T., Contreras J.A., Kimmel A.R., and Londos C. Perilipin A is essential for the translocation of hormone-sensitive lipase during lipolytic activation. J. Cell Biol. 161 (2003) 1093-1103 Erratum: J. Cell Biol. (2003). 162, 353
38. Martinez-Botas J., Anderson J.B., Tessier D., Lapillonne A., Chang B.H., Quast M.J., Gorenstein D., Chen K.H., and Chan L. Absence of perilipin results in leanness and reverses obesity in Lepr(db/db) mice. Nat. Genet. 26 (2000) 474-479
39. Mottagui-Tabar S., Ryden M., Lofgren P., Faulds G., Hoffstedt J., Brookes A.J., Andersson I., and Arner P. Evidence for an important role of perilipin in the regulation of human adipocyte lipolysis. Diabetologia 46 (2003) 789-797
40. Wang Y., Sullivan S., Trujillo M., Lee M.J., Schneider S.H., Brolin R.E., Kang Y.H., Werber Y., Greenberg A.S., and Fried S.K. Perilipin expression in human adipose tissues: effects of severe obesity, gender, and depot. Obes. Res. 11 (2003) 930-936
41. Jenkins-Kruchten A.E., Bennaars-Eiden A., Ross J.R., Shen W.J., Kraemer F.B., and Bernlohr D.A. Fatty acid-binding protein-hormone-sensitive lipase interaction. Fatty acid dependence on binding. J. Biol. Chem. 278 (2003) 47636-47643
42. Smith A.J., Sanders M.A., Thompson B.R., Londos C., Kraemer F.B., and Bernlohr D.A. Physical association between the adipocyte fatty acid-binding protein and hormone-sensitive lipase: a fluorescence resonance energy transfer analysis. J. Biol. Chem. 279 (2004) 52399-52405
43. Hertzel A.V., Smith L.A., Berg A.H., Cline G.W., Shulman G.I., Scherer P.E., and Bernlohr D.A. Lipid metabolism and adipokine levels in fatty acid-binding protein null and transgenic mice. Am. J. Physiol. Endocrinol. Metab. 290 (2006) E814-E823
44. Hotamisligil G.S., Johnson R.S., Distel R.J., Ellis R., Papaioannou V.E., and Spiegelman B.M. Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science 274 (1996) 1377-1379
45. Lafontan M., and Berlan M. Fat cell adrenergic receptors and the control of white and brown fat cell function. J. Lipid Res. 34 (1993) 1057-1091
46. Degerman E., Smith C.J., Tornqvist H., Vasta V., Belfrage P., and Manganiello V.C. Evidence that insulin and isoprenaline activate the cGMP-inhibited low-Km cAMP phosphodiesterase in rat fat cells by phosphorylation. Proc. Natl. Acad. Sci. USA 87 (1990) 533-537
47. Kitamura T., Kitamura Y., Kuroda S., Hino Y., Ando M., Kotani K., Konishi H., Matsuzaki H., Kikkawa U., Ogawa W., et al. Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt. Mol. Cell. Biol. 19 (1999) 6286-6296
48. Snyder P.B., Esselstyn J.M., Loughney K., Wolda S.L., and Florio V.A. The role of cyclic nucleotide phosphodiesterases in the regulation of adipocyte lipolysis. J. Lipid Res. 46 (2005) 494-503
49. Zhang Y., Schmidt R.J., Foxworthy P., Emkey R., Oler J.K., Large T.H., Wang H., Su E.W., Mosior M.K., Eacho P.I., et al. Niacin mediates lipolysis in adipose tissue through its G-protein coupled receptor HM74a. Biochem. Biophys. Res. Commun. 334 (2005) 729-732
50. Taggart A.K., Kero J., Gan X., Cai T.Q., Cheng K., Ippolito M., Ren N., Kaplan R., Wu K., Wu T.J., et al. (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J. Biol. Chem. 280 (2005) 26649-26652
51. Divertie G.D., Jensen M.D., and Miles J.M. Stimulation of lipolysis in humans by physiological hypercortisolemia. Diabetes 40 (1991) 1228-1232
52. Fruhbeck G., Gomez-Ambrosi J., and Salvador J. Leptin-induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes. FASEB J. 15 (2001) 333-340
53. Ryden M., Arvidsson E., Blomqvist L., Perbeck L., Dicker A., and Arner P. Targets for TNFα-induced lipolysis in human adipocytes. Biochem. Biophys. Res. Commun. 318 (2004) 168-175
54. Lyngso D., Simonsen L., and Bulow J. Interleukin-6 production in human subcutaneous abdominal adipose tissue: the effect of exercise. J. Physiol. 543 (2002) 373-378
55. Moro C., Galitzky J., Sengenes C., Crampes F., Lafontan M., and Berlan M. Functional and pharmacological characterization of the natriuretic peptide-dependent lipolytic pathway in human fat cells. J. Pharmacol. Exp. Ther. 308 (2003) 984-992
56. Engfeldt P., and Arner P. Lipolysis in human adipocytes, effects of cell size, age and of regional differences. Horm. Metab. Res. Suppl. 19 (1988) 26-29
57. Large V., Reynisdottir S., Langin D., Fredby K., Klannemark M., Holm C., and Arner P. Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects. J. Lipid Res. 40 (1999) 2059-2066
58. Bolinder J., Kerckhoffs D.A., Moberg E., Hagstrom-Toft E., and Arner P. Rates of skeletal muscle and adipose tissue glycerol release in nonobese and obese subjects. Diabetes 49 (2000) 797-802
59. Bougneres P., Stunff C.L., Pecqueur C., Pinglier E., Adnot P., and Ricquier D. In vivo resistance of lipolysis to epinephrine. A new feature of childhood onset obesity. J. Clin. Invest. 99 (1997) 2568-2573
60. Reynisdottir S., Wahrenberg H., Carlstrom K., Rossner S., and Arner P. Catecholamine resistance in fat cells of women with upper-body obesity due to decreased expression of β2-adrenoceptors. Diabetologia 37 (1994) 428-435
61. Langin D., Dicker A., Tavernier G., Hoffstedt J., Mairal A., Ryden M., Arner E., Sicard A., Jenkins C.M., Viguerie N., et al. Adipocyte lipases and defect of lipolysis in human obesity. Diabetes 54 (2005) 3190-3197
62. Mauriege P., Despres J.P., Prud'homme D., Pouliot M.C., Marcotte M., Tremblay A., and Bouchard C. Regional variation in adipose tissue lipolysis in lean and obese men. J. Lipid Res. 32 (1991) 1625-1633
63. Jensen M.D., Haymond M.W., Rizza R.A., Cryer P.E., and Miles J.M. Influence of body fat distribution on free fatty acid metabolism in obesity. J. Clin. Invest. 83 (1989) 1168-1173
64. Tan G.D., Goossens G.H., Humphreys S.M., Vidal H., and Karpe F. Upper and lower body adipose tissue function: a direct comparison of fat mobilization in humans. Obes. Res. 12 (2004) 114-118
65. Snijder M.B., Visser M., Dekker J.M., Goodpaster B.H., Harris T.B., Kritchevsky S.B., De Rekeneire N., Kanaya A.M., Newman A.B., Tylavsky F.A., and Seidell J.C. Low subcutaneous thigh fat is a risk factor for unfavourable glucose and lipid levels, independently of high abdominal fat. The Health ABC Study. Diabetologia 48 (2005) 301-308
66. 2. Metabolism 40 (1991) 990-996
67. Kabir M., Catalano K.J., Ananthnarayan S., Kim S.P., Van Citters G.W., Dea M.K., and Bergman R.N. Molecular evidence supporting the portal theory: a causative link between visceral adiposity and hepatic insulin resistance. Am. J. Physiol. Endocrinol. Metab. 288 (2005) E454-E461
68. Bergman R.N. Non-esterified fatty acids and the liver: why is insulin secreted into the portal vein?. Diabetologia 43 (2000) 946-952
69. Mittelman S.D., and Bergman R.N. Inhibition of lipolysis causes suppression of endogenous glucose production independent of changes in insulin. Am. J. Physiol. Endocrinol. Metab. 279 (2000) E630-E637
70. Petersen K.F., and Shulman G.I. New insights into the pathogenesis of insulin resistance in humans using magnetic resonance spectroscopy. Obesity (Silver Spring) 14 Suppl. 1 (2006) 34S-40S
71. Lorenzen A., Stannek C., Lang H., Andrianov V., Kalvinsh I., and Schwabe U. Characterization of a G protein-coupled receptor for nicotinic acid. Mol. Pharmacol. 59 (2001) 349-357
72. Wise A., Foord S.M., Fraser N.J., Barnes A.A., Elshourbagy N., Eilert M., Ignar D.M., Murdock P.R., Steplewski K., Green A., et al. Molecular identification of high and low affinity receptors for nicotinic acid. J. Biol. Chem. 278 (2003) 9869-9874
73. Soga T., Kamohara M., Takasaki J., Matsumoto S., Saito T., Ohishi T., Hiyama H., Matsuo A., Matsushime H., and Furuichi K. Molecular identification of nicotinic acid receptor. Biochem. Biophys. Res. Commun. 303 (2003) 364-369
74. Tunaru S., Kero J., Schaub A., Wufka C., Blaukat A., Pfeffer K., and Offermanns S. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat. Med. 9 (2003) 352-355
75. Schaub A., Futterer A., and Pfeffer K. PUMA-G, an IFN-gamma-inducible gene in macrophages is a novel member of the seven transmembrane spanning receptor superfamily. Eur. J. Immunol. 31 (2001) 3714-3725
76. Pike N.B., and Wise A. Identification of a nicotinic acid receptor: is this the molecular target for the oldest lipid-lowering drug?. Curr. Opin. Investig. Drugs 5 (2004) 271-275
77. Yousefi S., Cooper P.R., Mueck B., Potter S.L., and Jarai G. cDNA representational difference analysis of human neutrophils stimulated by GM-CSF. Biochem. Biophys. Res. Commun. 277 (2000) 401-409
78. van Herk T., Brussee J., van den Nieuwendijk A.M., van der Klein P.A., Ijzerman A.P., Stannek C., Burmeister A., and Lorenzen A. Pyrazole derivatives as partial agonists for the nicotinic acid receptor. J. Med. Chem. 46 (2003) 3945-3951
79. Seki K., Isegawa J., Fukuda M., and Ohki M. Studies on hypolipidemic agents. II. Synthesis and pharmacological properties of alkylpyrazole derivatives. Chem. Pharm. Bull. (Tokyo) 32 (1984) 1568-1577
80. Pinto, I.L., Rahman, S.S., and Nicholson, N.H. (2005). Preparation of xanthine derivatives as HM74A agonists. PCT Int. Appl. WO 2005077950.
81. Semple G., Skinner P.J., Cherrier M.C., Webb P.J., Sage C.R., Tamura S.Y., Chen R., Richman J.G., and Connolly D.T. 1-alkyl-benzotriazole-5-carboxylic acids are highly selective agonists of the human orphan G-protein-coupled receptor GPR109b. J. Med. Chem. 49 (2006) 1227-1230
82. Haemmerle G., Zimmermann R., Strauss J.G., Kratky D., Riederer M., Knipping G., and Zechner R. Hormone-sensitive lipase deficiency in mice changes the plasma lipid profile by affecting the tissue-specific expression pattern of lipoprotein lipase in adipose tissue and muscle. J. Biol. Chem. 277 (2002) 12946-12952
83. Sekiya M., Osuga J., Okazaki H., Yahagi N., Harada K., Shen W.J., Tamura Y., Tomita S., Iizuka Y., Ohashi K., et al. Absence of hormone-sensitive lipase inhibits obesity and adipogenesis in Lep ob/ob mice. J. Biol. Chem. 279 (2004) 15084-15090
84. Ollis D.L., Cheah E., Cygler M., Dijkstra B., Frolow F., Franken S.M., Harel M., Remington S.J., Silman I., Schrag J., et al. The α/β hydrolase fold. Protein Eng. 5 (1992) 197-211
85. Derewenda Z.S. Structure and function of lipases. Adv. Protein Chem. 45 (1994) 1-52
86. Osterlund T., Danielsson B., Degerman E., Contreras J.A., Edgren G., Davis R.C., Schotz M.C., and Holm C. Domain-structure analysis of recombinant rat hormone-sensitive lipase. Biochem. J. 319 (1996) 411-420
87. Contreras J.A., Karlsson M., Osterlund T., Laurell H., Svensson A., and Holm C. Hormone-sensitive lipase is structurally related to acetylcholinesterase, bile salt-stimulated lipase, and several fungal lipases. Building of a three-dimensional model for the catalytic domain of hormone-sensitive lipase. J. Biol. Chem. 271 (1996) 31426-31430
88. Wei Y., Contreras J.A., Sheffield P., Osterlund T., Derewenda U., Kneusel R.E., Matern U., Holm C., and Derewenda Z.S. Crystal structure of brefeldin A esterase, a bacterial homolog of the mammalian hormone-sensitive lipase. Nat. Struct. Biol. 6 (1999) 340-345
89. Perola E., Cellai L., Lamba D., Filocamo L., and Brufani M. Long chain analogs of physostigmine as potential drugs for Alzheimer's disease: new insights into the mechanism of action in the inhibition of acetylcholinesterase. Biochim. Biophys. Acta 1343 (1997) 41-50
90. Ebdrup S., Sorensen L.G., Olsen O.H., and Jacobsen P. Synthesis and structure-activity relationship for a novel class of potent and selective carbamoyl-triazole based inhibitors of hormone sensitive lipase. J. Med. Chem. 47 (2004) 400-410
91. Rampa A., Piazzi L., Belluti F., Gobbi S., Bisi A., Bartolini M., Andrisano V., Cavrini V., Cavalli A., Recanatini M., et al. Acetylcholinesterase inhibitors: SAR and kinetic studies on omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)methyl]aminoalkoxyaryl derivatives. J. Med. Chem. 44 (2001) 3810-3820
92. Petry, S., Schoenafinger, K., Mueller, G., and Baringhaus, K.-H. (2001). Preparation of 3-phenyl-5-alkoxy-1,3,4-oxadiazol-2-ones as hormone-sensitive lipase inhibitors. Ger. Offen. DE 19942354.
93. Schoenafinger, K., Petry, S., Mueller, G., and Baringhaus, K.-H. (2001). Preparation of 3-phenyl-5-alkoxy-1,3,4-oxadiazol-2-ones as inhibitors of hormone sensitive lipase (HSL). Ger. Offen. DE 10010968.
94. Lowe D.B., Magnuson S., Qi N., Campbell A.-M., Cook J., Hong Z., Wang M., Rodriguez M., Achebe F., Kluender H., et al. In vitro SAR of (5-(2H)-isoxazolonyl) ureas, potent inhibitors of hormone-sensitive lipase. Bioorg. Med. Chem. Lett. 14 (2004) 3155-3159
95. Claus T.H., Lowe D.B., Liang Y., Salhanick A.I., Lubeski C.K., Yang L., Lemoine L., Zhu J., and Clairmont K.B. Specific inhibition of hormone-sensitive lipase improves lipid profile while reducing plasma glucose. J. Pharmacol. Exp. Ther. 315 (2005) 1396-1402
96. de Souza C.J., and Burkey B.F. β3-adrenoceptor agonists as anti-diabetic and anti-obesity drugs in humans. Cur. Pharm. Des. 7 (2001) 1433-1449
97. Himms-Hagen J., and Ricquier D. Brown adipose tissue. In: Bray G.A., Bouchard C., and James W.P.T. (Eds). Handbook of Obesity (1998), M. Dekker, New York 415-441
98. Collins S., Cao W., and Robidoux J. Learning new tricks from old dogs: β-adrenergic receptors teach new lessons on firing up adipose tissue metabolism. Mol. Endocrinol. 18 (2004) 2123-2131
99. Lafontan M., Sengenes C., Galitzky J., Berlan M., De Glisezinski I., Crampes F., Stich V., Langin D., Barbe P., and Riviere D. Recent developments on lipolysis regulation in humans and discovery of a new lipolytic pathway. Int. J. Obes. Relat. Metab. Disord. 24 Suppl. 4 (2000) S47-S52
100. Walston J., Silver K., Bogardus C., Knowler W.C., Celi F.S., Austin S., Manning B., Strosberg A.D., Stern M.P., Raben N., et al. Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the β3-adrenergic-receptor gene. N. Engl. J. Med. 333 (1995) 343-347
101. Widen E., Lehto M., Kanninen T., Walston J., Shuldiner A.R., and Groop L.C. Association of a polymorphism in the β3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns. N. Engl. J. Med. 333 (1995) 348-351
102. Clement K., Vaisse C., Manning B.S., Basdevant A., Guy-Grand B., Ruiz J., Silver K.D., Shuldiner A.R., Froguel P., and Strosberg A.D. Genetic variation in the β3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. N. Engl. J. Med. 333 (1995) 352-354
103. Yoshida T., Sakane N., Umekawa T., Sakai M., Takahashi T., and Kondo M. Mutation of β3-adrenergic-receptor gene and response to treatment of obesity. Lancet 346 (1995) 1433-1434
104. Hu B., and Jennings L.J. Orally bioavailable β3-adrenergic receptor agonists as potential therapeutic agents for obesity ad type-II diabetes. Prog. Med. Chem. 41 (2003) 167-194
105. Nisoli E., Tonello C., and Carruba M.O. β3-adrenergic receptor: really relevant targets for anti-obesity drugs?. Curr. Med. Chem. Central Nervous System Agents 3 (2003) 257-273
106. Moule S.K., and Denton R.M. The activation of p38 MAPK by the β-adrenergic agonist isoproterenol in rat epididymal fat cells. FEBS Lett. 439 (1998) 287-290
107. Yin W., Mu J., and Birnbaum M.J. Role of AMP-activated protein kinase in cyclic AMP-dependent lipolysis in 3T3-L1 adipocytes. J. Biol. Chem. 278 (2003) 43074-43080
108. Sugimoto T., Ogawa W., Kasuga M., and Yokoyama Y. Chronic effects of AJ-9677 on energy expenditure and energy source utilization in rats. Eur. J. Pharmacol. 519 (2005) 135-145
109. Van Baak M.A., Hul G.B.J., Toubro S., Astrup A., Gottesdiener K.M., DeSmet M., and Saris W.H.M. Acute effect of L-796568, a novel β3-adrenergic receptor agonist, on energy expenditure in obese men. Clin. Pharmacol. Ther. 71 (2002) 272-279
110. Larsen T.M., Toubro S., van Baak M.A., Gottesdiener K.M., Larson P., Saris W.H.M., and Astrup A. Effect of a 28-d treatment with L-796568, a novel β3-adrenergic receptor agonist, on energy expenditure and body composition in obese men. Am. J. Clin. Nutr. 76 (2002) 780-788
111. Green A. Adenosine receptor down-regulation and insulin resistance following prolonged incubation of adipocytes with an A1 adenosine receptor agonist. J. Biol. Chem. 262 (1987) 15702-15707
112. Liang H.-X., Belardinelli L., Ozeck M.J., and Shryock J.C. Tonic activity of the rat adipocyte A1-adenosine receptor. Br. J. Pharmacol. 135 (2002) 1457-1466
113. Srinivas M., Shryock J.C., Dennis D.M., Baker S.P., and Belardinelli L. Differential A1 adenosine receptor reserve for two actions of adenosine on guinea pig atrial myocytes. Mol. Pharmacol. 52 (1997) 683-691
114. Fraser H., Gao Z., Ozeck M.J., and Belardinelli L. N-[3-(R)-tetrahydrofuranyl]-6-aminopurine riboside, an A1 adenosine receptor agonist, antagonizes catecholamine-induced lipolysis without cardiovascular effects in awake rats. J. Pharmacol. Exp. Ther. 305 (2003) 225-231
115. 1H-spectroscopy, and glucose clamp studies. Diabetes 53 (2004) 1920-1926
116. Dhalla A.K., Shryock J.C., Shreeniwas R., and Belardinelli L. Pharmacology and therapeutic applications of A1 adenosine receptor ligands. Curr. Top. Med. Chem. 3 (2003) 369-385
117. Haemmerle G., Lass A., Zimmermann R., Gorkiewicz G., Meyer C., Rozman J., Heldmaier G., Maier R., Theussl C., Eder S., et al. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 312 (2006) 734-737
118. Hatae N., Sugimoto Y., and Ichikawa A. Prostaglandin receptors: advances in the study of EP3 receptor signaling. J. Biochem. (Tokyo) 131 (2002) 781-784
119. Valet P., Berlan M., Beauville M., Crampes F., Montastruc J.L., and Lafontan M. Neuropeptide Y and peptide YY inhibit lipolysis in human and dog fat cells through a pertussis toxin-sensitive G protein. J. Clin. Invest. 85 (1990) 291-295
120. Sengenes C., Berlan M., De Glisezinski I., Lafontan M., and Galitzky J. Natriuretic peptides: a new lipolytic pathway in human adipocytes. FASEB J. 14 (2000) 1345-1351
121. Birkenfeld A.L., Boschmann M., Moro C., Adams F., Heusser K., Franke G., Berlan M., Luft F.C., Lafontan M., and Jordan J. Lipid mobilization with physiological atrial natriuretic peptide concentrations in humans. J. Clin. Endocrinol. Metab. 90 (2005) 3622-3628
122. Lafontan M., Moro C., Sengenes C., Galitzky J., Crampes F., and Berlan M. An unsuspected metabolic role for atrial natriuretic peptides: the control of lipolysis, lipid mobilization, and systemic nonesterified fatty acids levels in humans. Arterioscler. Thromb. Vasc. Biol. 25 (2005) 2032-2042