Stearoyl-CoA desaturase: A vital checkpoint in the development and progression of obesity

Endocrine, Metabolic and Immune Disorders - Drug Targets

Volumn 11, Issue 3, 2011, Pages 217-231

  Poudyal, Hemant ^a   Brown, Lindsay ^b  

^a UNIVERSITY OF QUEENSLAND   (Australia)

^b UNIVERSITY OF SOUTHERN QUEENSLAND   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ACYL COENZYME A DESATURASE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR;

ADIPOCYTE; CARBOHYDRATE METABOLISM; CELL DIFFERENTIATION; DISEASE COURSE; DRUG TARGETING; ENZYME REGULATION; FATTY ACID DESATURATION; FATTY ACID METABOLISM; FATTY ACID OXIDATION; GLUCOSE METABOLISM; HOMEOSTASIS; HUMAN; INFLAMMATION; LIPID METABOLISM; LIPOGENESIS; NONHUMAN; OBESITY; PREDICTION; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; THERMOGENESIS;

EID: 79961082162     PISSN: 18715303     EISSN: 18715303     Source Type: Journal    
DOI: 10.2174/187153011796429826     Document Type: Review

References (172)

1. Alberti, K. G.; Eckel, R. H.; Grundy, S. M.; Zimmet, P. Z.; Cleeman, J. I.; Donato, K. A.; Fruchart, J. C.; James, W. P.; Loria, C. M. and Smith, S. C., Jr. (2009) Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; american heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation, 120, 1640-1645.
2. Cameron, A. J.; Shaw, J. E. and Zimmet, P. Z. (2004) The metabolic syndrome: prevalence in worldwide populations. Endocrinol. Metab. Clin. North Am., 33, 351-375.
3. Cordain, L.; Eaton, S. B.; Sebastian, A.; Mann, N.; Lindeberg, S.; Watkins, B. A.; O'Keefe, J. H. and Brand-Miller, J. (2005) Origins and evolution of the Western diet: health implications for the 21st century. Am. J. Clin. Nutr., 81, 341-354.
4. Ogden, C. L.; Carroll, M. D.; Curtin, L. R.; McDowell, M. A.; Tabak, C. J. and Flegal, K. M. (2006) Prevalence of overweight and obesity in the United States, 1999-2004. JAMA, 295, 1549-1555.
5. Australian Institute of Health and Welfare 2010. Australia's health 2010. Australia's health series no. 12. Cat. no. AUS 122. Canberra: AIHW., 2010.
6. Mathavan, A.; Chockalingam, A.; Chockalingam, S.; Bilchik, B. and Saini, V. (2009) Madurai area physicians cardiovascular health evaluation survey (MAPCHES)--an alarming status. Can. J. Cardiol., 25, 303-308.
7. Ramachandran, A.; Snehalatha, C.; Satyavani, K.; Sivasankari, S. and Vijay, V. (2003) Metabolic syndrome in urban Asian Indian adults--a population study using modified ATP III criteria. Diab. Res. Clin. Practice, 60, 199-204.
8. Tian, H.; Xie, H.; Song, G.; Zhang, H. and Hu, G. (2009) Prevalence of overweight and obesity among 2.6 million rural Chinese adults. Prevent. Med., 48, 59-63.
9. Ravussin, E. and Bouchard, C. (2000) Human genomics and obesity: finding appropriate drug targets. Eur. J. Pharmacol., 410, 131-145.
10. Hansen, M. K. and Connolly, T. M. (2008) Nuclear receptors as drug targets in obesity, dyslipidemia and atherosclerosis. Curr. Opin. Invest. Dr., 9, 247-255.
11. Nair, R. P. and Ren, J. (2009) Pharmacotherapy of obesity - benefit, bias and hyperbole. Curr. Med. Chem., 16, 1888-1897.
12. Drewnowski, A. (2007) The real contribution of added sugars and fats to obesity. Epidemiol. Rev., 29, 160-171.
13. Tappy, L.; Le, K. A.; Tran, C. and Paquot, N. (2010) Fructose and metabolic diseases: New findings, new questions. Nutrition, 26(11-12), 1044-1049.
14. van Baak, M. A. and Astrup, A. (2009) Consumption of sugars and body weight. Obes. Rev., 10 Suppl 1, 9-23.
15. Siri-Tarino, P. W.; Sun, Q.; Hu, F. B. and Krauss, R. M. (2010) Saturated fat, carbohydrate, and cardiovascular disease. Am. J. Clin. Nutr., 91, 502-509.
16. Moussavi, N.; Gavino, V. and Receveur, O. (2007) Could the quality of dietary fat, and not just its quantity, be related to risk of obesity?. Obesity, 16, 7-15.
17. Flowers, M. T. and Ntambi, J. M. (2008) Role of stearoylcoenzyme A desaturase in regulating lipid metabolism. Curr. Opin. Lipidol., 19, 248-256.
18. Paton, C. M. and Ntambi, J. M. (2009) Biochemical and physiological function of stearoyl-CoA desaturase. Am. J. Physiol. Endocrinol. Metab., 297, E28-37.
19. Enoch, H. G.; Catala, A. and Strittmatter, P. (1976) Mechanism of rat liver microsomal stearyl-CoA desaturase. Studies of the substrate specificity, enzyme-substrate interactions, and the function of lipid. J. Biol. Chem., 251, 5095-5103.
20. Ntambi, J. M. (1999) Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol. J. Lipid. Res., 40, 1549-1558.
21. Mosley, E. E. and McGuire, M. A. (2007) Methodology for the in vivo measurement of the delta9-desaturation of myristic, palmitic, and stearic acids in lactating dairy cattle. Lipids, 42, 939-945.
22. Scaglia, N.; Chisholm, J. W. and Igal, R. A. (2009) Inhibition of stearoylCoA desaturase-1 inactivates acetyl-CoA carboxylase and impairs proliferation in cancer cells: role of AMPK. PLoS ONE, 4, e6812.
23. Hess, D.; Chisholm, J. W. and Igal, R. A. (2010) Inhibition of stearoylCoA desaturase activity blocks cell cycle progression and induces programmed cell death in lung cancer cells. PLoS ONE, 5, e11394.
24. Igal, R. A. (2010) Stearoyl-CoA desaturase-1: a novel key player in the mechanisms of cell proliferation, programmed cell death and transformation to cancer. Carcinogenesis, 31, 1509-1515.
25. Fritz, V.; Benfodda, Z.; Rodier, G.; Henriquet, C.; Iborra, F.; Avances, C.; Allory, Y.; de la Taille, A.; Culine, S.; Blancou, H.; Cristol, J. P.; Michel, F.; Sardet, C. and Fajas, L. (2010) Abrogation of de novo lipogenesis by stearoyl-CoA desaturase 1 inhibition interferes with oncogenic signaling and blocks prostate cancer progression in mice. Mol. Cancer Ther., 9, 1740-1754.
26. Dobrzyn, P.; Dobrzyn, A.; Miyazaki, M. and Ntambi, J. M. (2010) Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin deficient mice. J. Lipid Res., 51, 2202-2210.
27. Dobrzyn, P.; Jazurek, M. and Dobrzyn, A. (2010) Stearoyl-CoA desaturase and insulin signaling - What is the molecular switch? Biochim. Biophys. Acta., 1797, 1189-1194.
28. Cohen, P.; Miyazaki, M.; Socci, N. D.; Hagge-Greenberg, A.; Liedtke, W.; Soukas, A. A.; Sharma, R.; Hudgins, L. C.; Ntambi, J. M. and Friedman, J. M. (2002) Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science, 297, 240-243.
29. Cohen, P.; Ntambi, J. M. and Friedman, J. M. (2003) Stearoyl-CoA desaturase-1 and the metabolic syndrome. Curr. Drug Targets Immune Endocr. Metabol. Disord., 3, 271-280.
30. Sampath, H.; Miyazaki, M.; Dobrzyn, A. and Ntambi, J. M. (2007) Stearoyl-CoA desaturase-1 mediates the pro-lipogenic effects of dietary saturated fat. J. Biol. Chem., 282, 2483-2493.
31. Dobrzyn, P.; Dobrzyn, A.; Miyazaki, M.; Cohen, P.; Asilmaz, E.; Hardie, D. G.; Friedman, J. M. and Ntambi, J. M. (2004) Stearoyl- CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver. Proc. Natl. Acad. Sci. USA, 101, 6409-6414.
32. Dobrzyn, A.; Dobrzyn, P.; Lee, S. H.; Miyazaki, M.; Cohen, P.; Asilmaz, E.; Hardie, D. G.; Friedman, J. M. and Ntambi, J. M. (2005) Stearoyl-CoA desaturase-1 deficiency reduces ceramide synthesis by downregulating serine palmitoyltransferase and increasing beta-oxidation in skeletal muscle. Am. J. Physiol. Endocrinol. Metab., 288, E599-607.
33. Lee, S. H.; Dobrzyn, A.; Dobrzyn, P.; Rahman, S. M.; Miyazaki, M. and Ntambi, J. M. (2004) Lack of stearoyl-CoA desaturase 1 upregulates basal thermogenesis but causes hypothermia in a cold environment. J. Lipid. Res., 45, 1674-1682.
34. Dobrzyn, P.; Sampath, H.; Dobrzyn, A.; Miyazaki, M. and Ntambi, J. M. (2008) Loss of stearoyl-CoA desaturase 1 inhibits fatty acid oxidation and increases glucose utilization in the heart. Am. J. Physiol. Endocrinol. Metab., 294, E357-364.
35. Ntambi, J. M.; Miyazaki, M.; Stoehr, J. P.; Lan, H.; Kendziorski, C. M.; Yandell, B. S.; Song, Y.; Cohen, P.; Friedman, J. M. and Attie, A. D. (2002) Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proc. Natl. Acad. Sci. USA, 99, 11482-11486.
36. Park, S. Y.; Cho, Y. R.; Finck, B. N.; Kim, H. J.; Higashimori, T.; Hong, E. G.; Lee, M. K.; Danton, C.; Deshmukh, S.; Cline, G. W.; Wu, J. J.; Bennett, A. M.; Rothermel, B.; Kalinowski, A.; Russell, K. S.; Kim, Y. B.; Kelly, D. P. and Kim, J. K. (2005) Cardiacspecific overexpression of peroxisome proliferator-activated receptor-alpha causes insulin resistance in heart and liver. Diabetes, 54, 2514-2524.
37. Rahman, S. M.; Dobrzyn, A.; Lee, S. H.; Dobrzyn, P.; Miyazaki, M. and Ntambi, J. M. (2005) Stearoyl-CoA desaturase 1 deficiency increases insulin signaling and glycogen accumulation in brown adipose tissue. Am. J. Physiol. Endocrinol. Metab., 288, E381-387.
38. Jiang, G.; Li, Z.; Liu, F.; Ellsworth, K.; Dallas-Yang, Q.; Wu, M.; Ronan, J.; Esau, C.; Murphy, C.; Szalkowski, D.; Bergeron, R.; Doebber, T. and Zhang, B. B. (2005) Prevention of obesity in mice by antisense oligonucleotide inhibitors of stearoyl-CoA desaturase- 1. J. Clin. Invest., 115, 1030-1038.
39. Miyazaki, M.; Kim, Y. C.; Gray-Keller, M. P.; Attie, A. D. and Ntambi, J. M. (2000) 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., 275, 30132-30138.
40. Flowers, M. T. and Ntambi, J. M. (2009) Stearoyl-CoA desaturase and its relation to high-carbohydrate diets and obesity. Biochim. Biophys. Acta, 1791, 85-91.
41. Miyazaki, M.; Dobrzyn, A.; Man, W. C.; Chu, K.; Sampath, H.; Kim, H. J. and Ntambi, J. M. (2004) Stearoyl-CoA desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and -independent mechanisms. J. Biol. Chem., 279, 25164-25171.
42. Nakamura, M. T. and Nara, T. Y. (2002) Gene regulation of mammalian desaturases. Biochem. Soc. Trans., 30, 1076-1079.
43. Zhang, L.; Ge, L.; Parimoo, S.; Stenn, K. and Prouty, S. M. (1999) Human stearoyl-CoA desaturase: alternative transcripts generated from a single gene by usage of tandem polyadenylation sites. Biochem. J., 340 (Pt 1), 255-264.
44. Wang, J.; Yu, L.; Schmidt, R. E.; Su, C.; Huang, X.; Gould, K. and Cao, G. (2005) Characterization of HSCD5, a novel human stearoyl-CoA desaturase unique to primates. Biochem. Biophys. Res. Commun., 332, 735-742.
45. Zheng, Y.; Prouty, S. M.; Harmon, A.; Sundberg, J. P.; Stenn, K. S. and Parimoo, S. (2001) Scd3--a novel gene of the stearoyl-CoA desaturase family with restricted expression in skin. Genomics, 71, 182-191.
46. Tabor, D. E.; Xia, Y. R.; Mehrabian, M.; Edwards, P. A. and Lusis, A. J. (1998) A cluster of stearoyl CoA desaturase genes, Scd1 and Scd2, on mouse chromosome 19. Mamm. Genome, 9, 341-342.
47. Miyazaki, M.; Man, W. C. and Ntambi, J. M. (2001) 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., 131, 2260-2268.
48. Ntambi, J. M. and Miyazaki, M. (2003) Recent insights into stearoyl-CoA desaturase-1. Curr. Opin. Lipidol., 14, 255-261.
49. Miyazaki, M.; Dobrzyn, A.; Elias, P. M. and Ntambi, J. M. (2005) Stearoyl-CoA desaturase-2 gene expression is required for lipid synthesis during early skin and liver development. Proc. Natl. Acad. Sci. USA, 102, 12501-12506.
50. Miyazaki, M.; Jacobson, M. J.; Man, W. C.; Cohen, P.; Asilmaz, E.; Friedman, J. M. and Ntambi, J. M. (2003) Identification and characterization of murine SCD4, a novel heart-specific stearoyl- CoA desaturase isoform regulated by leptin and dietary factors. J. Biol. Chem., 278, 33904-33911.
51. Zhang, S.; Yang, Y. and Shi, Y. (2005) Characterization of human SCD2, an oligomeric desaturase with improved stability and enzyme activity by cross-linking in intact cells. Biochem. J., 388, 135-142.
52. Miyazaki, M.; Bruggink, S. M. and Ntambi, J. M. (2006) Identification of mouse palmitoyl-coenzyme A Delta9-desaturase. J. Lipid. Res., 47, 700-704.
53. Bellenger, J.; Bellenger, S.; Clement, L.; Mandard, S.; Diot, C.; Poisson, J. P. and Narce, M. (2004) A new hypotensive polyunsaturated fatty acid dietary combination regulates oleic acidaccumulation by suppression of stearoyl CoA desaturase 1 gene expression in the SHR model of genetic hypertension. FASEB J., 18, 773-775.
54. Ntambi, J. M. and Miyazaki, M. (2004) Regulation of stearoyl-CoA desaturases and role in metabolism. Prog. Lipid. Res., 43, 91-104.
55. Mainieri, D.; Montani, J. P.; Seydoux, J.; Giacobino, J. P.; Boss, O. and Dulloo, A. G. (2007) Beta-Adrenergic control of stearoyl-CoA desaturase 1 repression in relation to sympathoadrenal regulation of thermogenesis. Int. J. Obes. (Lond)., 31, 378-381.
56. Ferre, P. and Foufelle, F. (2007) SREBP-1c transcription factor and lipid homeostasis: clinical perspective. Horm. Res., 68, 72-82.
57. Postic, C.; Dentin, R.; Denechaud, P. D. and Girard, J. (2007) ChREBP, a transcriptional regulator of glucose and lipid metabolism. Annu. Rev. Nutr., 27, 179-192.
58. Dentin, R.; Girard, J. and Postic, C. (2005) Carbohydrate responsive element binding protein (ChREBP) and sterol regulatory element binding protein-1c (SREBP-1c): two key regulators of glucose metabolism and lipid synthesis in liver. Biochimie, 87, 81-86.
59. Miyazaki, M.; Kim, Y. C. and Ntambi, J. M. (2001) A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis. J. Lipid Res., 42, 1018-1024.
60. Denechaud, P. D.; Girard, J. and Postic, C. (2008) Carbohydrate responsive element binding protein and lipid homeostasis. Curr. Opin. Lipidol., 19, 301-306.
61. Kim, H. J.; Miyazaki, M. and Ntambi, J. M. (2002) Dietary cholesterol opposes PUFA-mediated repression of the stearoyl- CoA desaturase-1 gene by SREBP-1 independent mechanism. J. Lipid Res., 43, 1750-1757.
62. Chen, G.; Liang, G.; Ou, J.; Goldstein, J. L. and Brown, M. S. (2004) Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver. Proc. Natl. Acad. Sci. USA, 101, 11245-11250.
63. Cha, J. Y. and Repa, J. J. (2007) The liver X receptor (LXR) and hepatic lipogenesis. The carbohydrate-response element-binding protein is a target gene of LXR. J. Biol. Chem., 282, 743-751.
64. Chu, K.; Miyazaki, M.; Man, W. C. and Ntambi, J. M. (2006) Stearoyl-coenzyme A desaturase 1 deficiency protects against hypertriglyceridemia and increases plasma high-density lipoprotein cholesterol induced by liver X receptor activation. Mol. Cell Biol., 26, 6786-6798.
65. Liang, G.; Yang, J.; Horton, J. D.; Hammer, R. E.; Goldstein, J. L. and Brown, M. S. (2002) Diminished hepatic response to fasting/ refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c. J. Biol. Chem., 277, 9520-9528.
66. Iizuka, K.; Bruick, R. K.; Liang, G.; Horton, J. D. and Uyeda, K. (2004) Deficiency of carbohydrate response element-binding protein (ChREBP) reduces lipogenesis as well as glycolysis. Proc. Natl. Acad. Sci. USA, 101, 7281-7286.
67. Sampath, H. and Ntambi, J. M. (2005) Polyunsaturated fatty acid regulation of genes of lipid metabolism. Annu. Rev. Nutr., 25, 317-340.
68. Jump, D. B. (2008) N-3 polyunsaturated fatty acid regulation of hepatic gene transcription. Curr. Opin. Lipidol., 19, 242-247.
69. Ntambi, J. M. (1992) Dietary regulation of stearoyl-CoA desaturase 1 gene expression in mouse liver. J. Biol. Chem., 267, 10925-10930.
70. Repa, J. J.; Liang, G.; Ou, J.; Bashmakov, Y.; Lobaccaro, J. M.; Shimomura, I.; Shan, B.; Brown, M. S.; Goldstein, J. L. and Mangelsdorf, D. J. (2000) Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev., 14, 2819-2830.
71. Landau, J. M.; Sekowski, A. and Hamm, M. W. (1997) Dietary cholesterol and the activity of stearoyl CoA desaturase in rats: evidence for an indirect regulatory effect. Biochim. Biophys. Acta., 1345, 349-357.
72. Landschulz, K. T.; Jump, D. B.; MacDougald, O. A. and Lane, M. D. (1994) Transcriptional control of the stearoyl-CoA desaturase-1 gene by polyunsaturated fatty acids. Biochem. Biophys. Res. Commun., 200, 763-768.
73. Caputo, M.; Zirpoli, H.; Torino, G. and Tecce, M. F. (2011) Selective regulation of UGT1A1 and SREBP-1c mRNA expression by Docosahexaenoic, eicosapentaenoic and arachidonic acids. J. Cell Physiol., 226, 187-193.
74. Tabor, D. E.; Kim, J. B.; Spiegelman, B. M. and Edwards, P. A. (1999) Identification of conserved cis-elements and transcription factors required for sterol-regulated transcription of stearoyl-CoA desaturase 1 and 2. J. Biol. Chem., 274, 20603-20610.
75. Bene, H.; Lasky, D. and Ntambi, J. M. (2001) Cloning and characterization of the human stearoyl-CoA desaturase gene promoter: transcriptional activation by sterol regulatory element binding protein and repression by polyunsaturated fatty acids and cholesterol. Biochem. Biophys. Res. Commun., 284, 1194-1198.
76. Waters, K. M.; Miller, C. W. and Ntambi, J. M. (1997) Localization of a polyunsaturated fatty acid response region in stearoyl-CoA desaturase gene 1. Biochim. Biophys. Acta., 1349, 33-42.
77. Jazurek, M.; Dobrzyn, P.; Szerbart, A.; Ntambi, J. M. and Dobrzyn, A. (2010) The role of stearoyl-CoA desaturase 1 in the development of obesity related insulin resistance. Chem. Phys. Lipids, 163, S60-S60.
78. Liu, X.; Miyazaki, M.; Flowers, M. T.; Sampath, H.; Zhao, M.; Chu, K.; Paton, C. M.; Joo, D. S. and Ntambi, J. M. (2010) Loss of Stearoyl-CoA desaturase-1 attenuates adipocyte inflammation: effects of adipocyte-derived oleate. Arterioscler. Thromb. Vasc. Biol., 30, 31-38.
79. Wiczer, B. M.; Lobo, S.; Machen, G. L.; Graves, L. M. and Bernlohr, D. A. (2009) FATP1 mediates fatty acid-induced activation of AMPK in 3T3-L1 adipocytes. Biochem. Biophys. Res. Commun., 387, 234-238.
80. Watt, M. J.; Steinberg, G. R.; Chen, Z. P.; Kemp, B. E. and Febbraio, M. A. (2006) Fatty acids stimulate AMP-activated protein kinase and enhance fatty acid oxidation in L6 myotubes. J. Physiol., 574, 139-147.
81. Wang, X.; Zhou, L.; Li, G.; Luo, T.; Gu, Y.; Qian, L.; Fu, X.; Li, F.; Li, J. and Luo, M. (2007) Palmitate activates AMP-activated protein kinase and regulates insulin secretion from beta cells. Biochem. Biophys. Res. Commun., 352, 463-468.
82. Yoon, M. (2009) The role of PPARalpha in lipid metabolism and obesity: focusing on the effects of estrogen on PPARalpha actions. Pharmacol. Res., 60, 151-159.
83. Guzman-Ruiz, R.; Somoza, B.; Gil-Ortega, M.; Merino, B.; Cano, V.; Attane, C.; Castan-Laurell, I.; Valet, P.; Fernandez-Alfonso, M. S. and Ruiz-Gayo, M. (2010) Sensitivity of cardiac carnitine palmitoyltransferase to malonyl-CoA is regulated by leptin: similarities with a model of endogenous hyperleptinemia. Endocrinology, 151, 1010-1018.
84. Suzuki, A.; Okamoto, S.; Lee, S.; Saito, K.; Shiuchi, T. and Minokoshi, Y. (2007) Leptin stimulates fatty acid oxidation and peroxisome proliferator-activated receptor alpha gene expression in mouse C2C12 myoblasts by changing the subcellular localization of the alpha2 form of AMP-activated protein kinase. Mol. Cell Biol., 27, 4317-4327.
85. Turyn, J.; Stojek, M. and Swierczynski, J. (2010) Up-regulation of stearoyl-CoA desaturase 1 and elongase 6 genes expression in rat lipogenic tissues by chronic food restriction and chronic food restriction/refeeding. Mol. Cell Biochem., 345, 181-188.
86. Liu, W. H.; Lin, C. C.; Wang, Z. H.; Mong, M. C. and Yin, M. C. (2010) Effects of protocatechuic acid on trans fat induced hepatic steatosis in mice. J. Agric. Food Chem., 58, 10247-10252.
87. Yu, W.; Liang, X.; Ensenauer, R. E.; Vockley, J.; Sweetman, L. and Schulz, H. (2004) Leaky beta-oxidation of a trans-fatty acid: incomplete beta-oxidation of elaidic acid is due to the accumulation of 5-trans-tetradecenoyl-CoA and its hydrolysis and conversion to 5-trans-tetradecenoylcarnitine in the matrix of rat mitochondria. J. Biol. Chem., 279, 52160-52167.
88. Kuhnt, K.; Kraft, J.; Moeckel, P. and Jahreis, G. (2006) Trans-11- 18: 1 is effectively Delta9-desaturated compared with trans-12-18: 1 in humans. Br. J. Nutr., 95, 752-761.
89. Wu, Z.; Li, D. and Gou, K. (2010) Overexpression of stearoyl-CoA desaturase-1 results in an increase of conjugated linoleic acid (CLA) and n-7 fatty acids in 293 cells. Biochem. Biophys. Res. Commun., 398, 473-476.
90. Das, U. N. (2006) Essential fatty acids - a review. Curr. Pharm. Biotechnol., 7, 467-482.
91. Shulman, G. I. (2000) Cellular mechanisms of insulin resistance. J. Clin. Invest., 106, 171-176.
92. Stanhope, K. L. and Havel, P. J. (2008) Fructose consumption: potential mechanisms for its effects to increase visceral adiposity and induce dyslipidemia and insulin resistance. Curr. Opin. Lipidol., 19, 16-24.
93. Buettner, R.; Scholmerich, J. and Bollheimer, L. C. (2007) High-fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity (Silver Spring), 15, 798-808.
94. Poudyal, H.; Campbell, F. and Brown, L. (2010) Olive leaf extract attenuates cardiac, hepatic, and metabolic changes in high carbohydrate-, high fat-fed rats. J. Nutr., 140, 946-953.
95. Choi, K. and Kim, Y. B. (2010) Molecular mechanism of insulin resistance in obesity and type 2 diabetes. Korean J. Intern. Med., 25, 119-129.
96. Voss, M. D.; Beha, A.; Tennagels, N.; Tschank, G.; Herling, A. W.; Quint, M.; Gerl, M.; Metz-Weidmann, C.; Haun, G. and Korn, M. (2005) Gene expression profiling in skeletal muscle of Zucker diabetic fatty rats: implications for a role of stearoyl-CoA desaturase 1 in insulin resistance. Diabetologia, 48, 2622-2630.
97. Gutierrez-Juarez, R.; Pocai, A.; Mulas, C.; Ono, H.; Bhanot, S.; Monia, B. P. and Rossetti, L. (2006) Critical role of stearoyl-CoA desaturase-1 (SCD1) in the onset of diet-induced hepatic insulin resistance. J. Clin. Invest., 116, 1686-1695.
98. Miyazaki, M.; Flowers, M. T.; Sampath, H.; Chu, K.; Otzelberger, C.; Liu, X. and Ntambi, J. M. (2007) Hepatic stearoyl-CoA desaturase-1 deficiency protects mice from carbohydrate-induced adiposity and hepatic steatosis. Cell. Metab., 6, 484-496.
99. Yechoor, V. K.; Patti, M. E.; Ueki, K.; Laustsen, P. G.; Saccone, R.; Rauniyar, R. and Kahn, C. R. (2004) Distinct pathways of insulin-regulated versus diabetes-regulated gene expression: an in vivo analysis in MIRKO mice. Proc. Natl. Acad. Sci. USA, 101, 16525-16530.
100. Thorens, B. and Mueckler, M. (2010) Glucose transporters in the 21st Century. Am. J. Physiol. Endocrinol. Metab., 298, E141-145.
101. Rahman, S. M.; Dobrzyn, A.; Dobrzyn, P.; Lee, S. H.; Miyazaki, M. and Ntambi, J. M. (2003) Stearoyl-CoA desaturase 1 deficiency elevates insulin-signaling components and down-regulates proteintyrosine phosphatase 1B in muscle. Proc. Natl. Acad. Sci. USA, 100, 11110-11115.
102. Hyun, C. K.; Kim, E. D.; Flowers, M. T.; Liu, X.; Kim, E.; Strable, M. and Ntambi, J. M. (2010) Adipose-specific deletion of stearoyl- CoA desaturase 1 up-regulates the glucose transporter GLUT1 in adipose tissue. Biochem. Biophys. Res. Commun., 399, 480-486.
103. Summers, S. A. (2010) Sphingolipids and insulin resistance: the five Ws. Curr. Opin. Lipidol., 21, 128-135.
104. Warensjo, E.; Ingelsson, E.; Lundmark, P.; Lannfelt, L.; Syvanen, A. C.; Vessby, B. and Riserus, U. (2007) Polymorphisms in the SCD1 gene: associations with body fat distribution and insulin sensitivity. Obesity (Silver Spring), 15, 1732-1740.
105. Yao-Borengasser, A.; Rassouli, N.; Varma, V.; Bodles, A. M.; Rasouli, N.; Unal, R.; Phanavanh, B.; Ranganathan, G.; McGehee, R. E., Jr. and Kern, P. A. (2008) Stearoyl-coenzyme a desaturase 1 gene expression increases after pioglitazone treatment and is associated with peroxisomal proliferator-activated receptorgamma responsiveness. J. Clin. Endocrinol. Metab., 93, 4431- 4439.
106. Brown, J. M.; Chung, S.; Sawyer, J. K.; Degirolamo, C.; Alger, H. M.; Nguyen, T.; Zhu, X.; Duong, M. N.; Wibley, A. L.; Shah, R.; Davis, M. A.; Kelley, K.; Wilson, M. D.; Kent, C.; Parks, J. S. and Rudel, L. L. (2008) Inhibition of stearoyl-coenzyme A desaturase 1 dissociates insulin resistance and obesity from atherosclerosis. Circulation, 118, 1467-1475.
107. MacDonald, M. L. E.; Bissada, N.; Vallance, B. A. and Hayden, M. R. (2009) Absence of stearoyl-CoA desaturase-1 does not promote DSS-induced acute colitis. Biochimica et Biophysica Acta (BBA) - Mol. Cell Biol. Lipids, 1791, 1166-1172.
108. Chen, C.; Shah, Y. M.; Morimura, K.; Krausz, K. W.; Miyazaki, M.; Richardson, T. A.; Morgan, E. T.; Ntambi, J. M.; Idle, J. R. and Gonzalez, F. J. (2008) Metabolomics reveals that hepatic stearoyl- CoA desaturase 1 downregulation exacerbates inflammation and acute colitis. Cell Metab., 7, 135-147.
109. MacDonald, M. L.; van Eck, M.; Hildebrand, R. B.; Wong, B. W.; Bissada, N.; Ruddle, P.; Kontush, A.; Hussein, H.; Pouladi, M. A.; Chapman, M. J.; Fievet, C.; van Berkel, T. J.; Staels, B.; McManus, B. M. and Hayden, M. R. (2009) Despite antiatherogenic metabolic characteristics, SCD1-deficient mice have increased inflammation and atherosclerosis. Arterioscler. Thromb. Vasc. Biol., 29, 341-347.
110. Brown, J. M.; Chung, S.; Sawyer, J. K.; Degirolamo, C.; Alger, H. M.; Nguyen, T. M.; Zhu, X.; Duong, M. N.; Brown, A. L.; Lord, C.; Shah, R.; Davis, M. A.; Kelley, K.; Wilson, M. D.; Madenspacher, J.; Fessler, M. B.; Parks, J. S. and Rudel, L. L. (2010) Combined therapy of dietary fish oil and stearoyl-CoA desaturase 1 inhibition prevents the metabolic syndrome and atherosclerosis. Arterioscler. Thromb. Vasc. Biol., 30, 24-30.
111. Peter, A.; Weigert, C.; Staiger, H.; Machicao, F.; Schick, F.; Machann, J.; Stefan, N.; Thamer, C.; Haring, H. U. and Schleicher, E. (2009) Individual stearoyl-coa desaturase 1 expression modulates endoplasmic reticulum stress and inflammation in human myotubes and is associated with skeletal muscle lipid storage and insulin sensitivity in vivo. Diabetes, 58, 1757-1765.
112. Moreno, M.; Lombardi, A.; Silvestri, E.; Senese, R.; Cioffi, F.; Goglia, F.; Lanni, A. and de Lange, P. (2010) PPARs: Nuclear receptors controlled by, and controlling, nutrient handling through nuclear and cytosolic signaling. PPAR Res., 2010, Epub 2010 Aug 1.
113. Burri, L.; Thoresen, G. H. and Berge, R. K. (2010) The role of PPARalpha activation in liver and muscle. PPAR Res., 2010, Epub 2010 Aug 18.
114. Wagner, K.-D. and Wagner, N. (2010) Peroxisome proliferatoractivated receptor beta/delta (PPAR[beta]/[delta]) acts as regulator of metabolism linked to multiple cellular functions. Pharma. Therapeutics, 125, 423-435.
115. Bishop-Bailey, D. and Bystrom, J. (2009) Emerging roles of peroxisome proliferator-activated receptor-beta/delta in inflammation. Pharmacol. Ther., 124, 141-150.
116. Hebbachi, A. M.; Knight, B. L.; Wiggins, D.; Patel, D. D. and Gibbons, G. F. (2008) Peroxisome proliferator-activated receptor alpha deficiency abolishes the response of lipogenic gene expression to re-feeding: restoration of the normal response by activation of liver X receptor alpha. J. Biol. Chem., 283, 4866-4876.
117. Miyazaki, M.; Dobrzyn, A.; Sampath, H.; Lee, S. H.; Man, W. C.; Chu, K.; Peters, J. M.; Gonzalez, F. J. and Ntambi, J. M. (2004) Reduced adiposity and liver steatosis by stearoyl-CoA desaturase deficiency are independent of peroxisome proliferator-activated receptor-alpha. J. Biol. Chem., 279, 35017-35024.
118. Yamazaki, T.; Shiraishi, S.; Kishimoto, K.; Miura, S. and Ezaki, O. (2010) An increase in liver PPARgamma2 is an initial event to induce fatty liver in response to a diet high in butter: PPARgamma2 knockdown improves fatty liver induced by highsaturated fat. J. Nutr. Biochem., [Epub ahead of print]
119. Martinez-Gonzalez, M. A. and Bes-Rastrollo, M. (2006) The cardioprotective benefits of monounsaturated fatty acid. Altern. Ther. Health Med., 12, 24-30; quiz 31.
120. Babio, N.; Bullo, M. and Salas-Salvado, J. (2009) Mediterranean diet and metabolic syndrome: the evidence. Public Health Nutr., 12, 1607-1617.
121. Piers, L. S.; Walker, K. Z.; Stoney, R. M.; Soares, M. J. and O'Dea, K. (2002) The influence of the type of dietary fat on postprandial fat oxidation rates: monounsaturated (olive oil) vs saturated fat (cream). Int. J. Obes. Relat. Metab. Disord., 26, 814-821.
122. Bos, M. B.; de Vries, J. H.; Feskens, E. J.; van Dijk, S. J.; Hoelen, D. W.; Siebelink, E.; Heijligenberg, R. and de Groot, L. C. (2010) Effect of a high monounsaturated fatty acids diet and a Mediterranean diet on serum lipids and insulin sensitivity in adults with mild abdominal obesity. Nutr. Metab. Cardiovasc. Dis., 20, 591-598.
123. Brunerova, L.; Smejkalova, V.; Potockova, J. and Andel, M. (2007) A comparison of the influence of a high-fat diet enriched in monounsaturated fatty acids and conventional diet on weight loss and metabolic parameters in obese non-diabetic and Type 2 diabetic patients. Diabet. Med., 24, 533-540.
124. Paniagua, J. A.; Gallego de la S. A.; Romero, I.; Vidal-Puig, A.; Latre, J. M.; Sanchez, E.; Perez-Martinez, P.; Lopez- Miranda, J. and Perez-Jimenez, F. (2007) Monounsaturated fat-rich diet prevents central body fat distribution and decreases postprandial adiponectin expression induced by a carbohydrate-rich diet in insulin-resistant subjects. Diabetes Care, 30, 1717-1723.
125. Ellis, J.; Lake, A. and Hoover-Plow, J. (2002) Monounsaturated canola oil reduces fat deposition in growing female rats fed a high or low fat diet. Nutr. Res., 22, 609-621.
126. Tsunoda, N.; Ikemoto, S.; Takahashi, M.; Maruyama, K.; Watanabe, H.; Goto, N. and Ezaki, O. (1998) High-monounsaturated fat dietinduced obesity and diabetes in C57BL/6J mice. Metabolism, 47, 724-730.
127. Paillard, F.; Catheline, D.; Duff, F. L.; Bouriel, M.; Deugnier, Y.; Pouchard, M.; Daubert, J. C. and Legrand, P. (2008) Plasma palmitoleic acid, a product of stearoyl-coA desaturase activity, is an independent marker of triglyceridemia and abdominal adiposity. Nutr. Metab. Cardiovasc. Dis., 18, 436-440.
128. Siri-Tarino, P. W.; Sun, Q.; Hu, F. B. and Krauss, R. M. Saturated fat, carbohydrate, and cardiovascular disease. Am. J. Clin. Nutr., 91, 502-509.
129. Hall, W. L. (2009) Dietary saturated and unsaturated fats as determinants of blood pressure and vascular function. Nutr. Res. Rev., 22, 18-38.
130. Kris-Etherton, P. M.; Griel, A. E.; Psota, T. L.; Gebauer, S. K.; Zhang, J. and Etherton, T. D. (2005) Dietary stearic acid and risk of cardiovascular disease: intake, sources, digestion, and absorption. Lipids, 40, 1193-1200.
131. Kitajima, K.; Tashiro, S. and Numa, S. (1975) Acetyl-coenzyme-A carboxylase in cultured hepatocytes. Effects of exogenous fatty acids on the content, synthesis and degradation of the enzyme. Eur. J. Biochem., 54, 373-383.
132. Brun, T.; Assimacopoulos-Jeannet, F.; Corkey, B. E. and Prentki, M. (1997) Long-chain fatty acids inhibit acetyl-CoA carboxylase gene expression in the pancreatic beta-cell line INS-1. Diabetes, 46, 393-400.
133. Goodridge, A. G. (1972) Regulation of the activity of acetyl coenzyme A carboxylase by palmitoyl coenzyme A and citrate. J. Biol. Chem., 247, 6946-6952.
134. Clapham, J. C. and Arch, J. R. (2007) Thermogenic and metabolic antiobesity drugs: rationale and opportunities. Diabetes Obes. Metab., 9, 259-275.
135. Attie, A. D.; Krauss, R. M.; Gray-Keller, M. P.; Brownlie, A.; Miyazaki, M.; Kastelein, J. J.; Lusis, A. J.; Stalenhoef, A. F.; Stoehr, J. P.; Hayden, M. R. and Ntambi, J. M. (2002) Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia. J. Lipid Res., 43, 1899-1907.
136. Riserus, U.; Tan, G. D.; Fielding, B. A.; Neville, M. J.; Currie, J.; Savage, D. B.; Chatterjee, V. K.; Frayn, K. N.; O'Rahilly, S. and Karpe, F. (2005) Rosiglitazone increases indexes of stearoyl-CoA desaturase activity in humans: link to insulin sensitization and the role of dominant-negative mutation in peroxisome proliferatoractivated receptor-gamma. Diabetes, 54, 1379-1384.
137. Pauciullo, A.; Cosenza, G.; D'Avino, A.; Colimoro, L.; Nicodemo, D.; Coletta, A.; Feligini, M.; Marchitelli, C.; Di Berardino, D. and Ramunno, L. (2010) Sequence analysis and genetic variability of stearoyl CoA desaturase (SCD) gene in the Italian Mediterranean river buffalo. Mol. Cell Probes., 24, 407-410.
138. Melhus, H.; Riserus, U.; Warensjo, E.; Wernroth, L.; Jensevik, K.; Berglund, L.; Vessby, B. and Michaelsson, K. (2008) A high activity index of stearoyl-CoA desaturase is associated with increased risk of fracture in men. Osteoporos Int., 19, 929-934.
139. Flowers, M. T. (2009) The delta9 fatty acid desaturation index as a predictor of metabolic disease. Clin. Chem., 55, 2071-2073.
140. Petersson, H.; Arnlov, J.; Zethelius, B. and Riserus, U. (2010) Serum fatty acid composition and insulin resistance are independently associated with liver fat markers in elderly men. Diabetes Res. Clin. Pract., 87, 379-384.
141. Araya, J.; Rodrigo, R.; Videla, L. A.; Thielemann, L.; Orellana, M.; Pettinelli, P. and Poniachik, J. (2004) Increase in long-chain polyunsaturated fatty acid n - 6/n - 3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease. Clin. Sci. (Lond)., 106, 635-643.
142. Shimomura, I.; Shimano, H.; Korn, B. S.; Bashmakov, Y. and Horton, J. D. (1998) Nuclear sterol regulatory element-binding proteins activate genes responsible for the entire program of unsaturated fatty acid biosynthesis in transgenic mouse liver. J. Biol. Chem., 273, 35299-35306.
143. Karpe, F. and Hodson, L. (2008) Caution on the Interpretation of Plasma Fatty Acid Composition as a Proxy Marker for SCD1 Activity: Particular Implications for Using the 16:1/16:0 Ratio in QTL Studies Involving Hyperlipidemic Patients. Arterioscler. Thromb. Vasc. Biol., 28, e152.
144. Hodson, L.; Skeaff, C. M. and Fielding, B. A. (2008) Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. Progress Lipid Res., 47, 348-380.
145. Liu, G. (2009) Stearoyl-CoA desaturase inhibitors: update on patented compounds. Expert Opin. Ther. Pat., 19, 1169-1191.
146. Atkinson, K. A.; Beretta, E. E.; Brown, J. A.; Castrodad, M.; Chen, Y.; Cosgrove, J. M.; Du, P.; Litchfield, J.; Makowski, M.; Martin, K.; McLellan, T. J.; Neagu, C.; Perry, D. A.; Piotrowski, D. W.; Steppan, C. M. and Trilles, R. (2011) N-Benzylimidazole carboxamides as potent, orally active stearoylCoA desaturase-1 inhibitors. Bioorg. Med. Chem. Lett., Epub 2011 Jan 31.
147. Uto, Y.; Ogata, T.; Harada, J.; Kiyotsuka, Y.; Ueno, Y.; Miyazawa, Y.; Kurata, H.; Deguchi, T.; Watanabe, N.; Takagi, T.; Wakimoto, S.; Okuyama, R.; Abe, M.; Kurikawa, N.; Kawamura, S.; Yamato, M. and Osumi, J. (2009) Novel and potent inhibitors of stearoyl- CoA desaturase-1. Part I: Discovery of 3-(2-hydroxyethoxy)-4- methoxy-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]b enzamide. Bioorg. Med. Chem. Lett., 19, 4151-4158.
148. Uto, Y.; Ogata, T.; Kiyotsuka, Y.; Miyazawa, Y.; Ueno, Y.; Kurata, H.; Deguchi, T.; Yamada, M.; Watanabe, N.; Takagi, T.; Wakimoto, S.; Okuyama, R.; Konishi, M.; Kurikawa, N.; Kono, K. and Osumi, J. (2009) Novel and potent inhibitors of stearoyl-CoA desaturase-1. Part II: Identification of 4-ethylamino-3-(2- hydroxyethoxy)-N-[5-(3-trifluoromethylbenzyl)thiazol-2-y l]benzamide and its biological evaluation. Bioorg. Med. Chem. Lett., 19, 4159-4166.
149. Uto, Y.; Ueno, Y.; Kiyotsuka, Y.; Miyazawa, Y.; Kurata, H.; Ogata, T.; Yamada, M.; Deguchi, T.; Konishi, M.; Takagi, T.; Wakimoto, S. and Ohsumi, J. (2010) Synthesis and evaluation of novel stearoyl-CoA desaturase 1 inhibitors: 1'-{6-[5-(pyridin- 3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3,4-dih ydrospiro [chromene-2,4'-piperidine] analogs. Eur. J. Med. Chem., 45, 4788-4796.
150. Koltun, D. O.; Vasilevich, N. I.; Parkhill, E. Q.; Glushkov, A. I.; Zilbershtein, T. M.; Mayboroda, E. I.; Boze, M. A.; Cole, A. G.; Henderson, I.; Zautke, N. A.; Brunn, S. A.; Chu, N.; Hao, J.; Mollova, N.; Leung, K.; Chisholm, J. W. and Zablocki, J. (2009) Orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors. Bioorg. Med. Chem. Lett., 19, 3050-3053.
151. Leger, S.; Black, W. C.; Deschenes, D.; Dolman, S.; Falgueyret, J. P.; Gagnon, M.; Guiral, S.; Huang, Z.; Guay, J.; Leblanc, Y.; Li, C. S.; Masse, F.; Oballa, R. and Zhang, L. (2010) Synthesis and biological activity of a potent and orally bioavailable SCD inhibitor (MF-438). Bioorg. Med. Chem. Lett., 20, 499-502.
152. Li, C. S.; Belair, L.; Guay, J.; Murgasva, R.; Sturkenboom, W.; Ramtohul, Y. K.; Zhang, L. and Huang, Z. (2009) Thiazole analog as stearoyl-CoA desaturase 1 inhibitor. Bioorg. Med. Chem. Lett., 19, 5214-5217.
153. Yokozawa, J.; Sasaki, T.; Ohwada, K.; Sasaki, Y.; Ito, J. I.; Saito, T. and Kawata, S. (2009) Down-regulation of hepatic stearoyl-CoA desaturase 1 expression by angiotensin II receptor blocker in the obese fa/fa Zucker rat: possible role in amelioration of insulin resistance and hepatic steatosis. J. Gastroenterol., 44, 583-591.
154. Terrazzino, S.; Berto, F.; Dalle Carbonare, M.; Fabris, M.; Guiotto, A.; Bernardini, D. and Leon, A. (2004) Stearoylethanolamide exerts anorexic effects in mice via down-regulation of liver stearoyl-coenzyme A desaturase-1 mRNA expression. FASEB J., 18, 1580-1582.
155. Poudyal, H.; Panchal, S.; Waanders, J.; Ward, L. and Brown, L. (2011) Lipid redistribution by α-linolenic acid-rich chia seed inhibits stearoyl-CoA desaturase-1 and induces cardiac and hepatic protection in diet-induced obese rats. J. Nutr. Biochem., [Epub ahead of print].
156. Samuel, V. T.; Petersen, K. F. and Shulman, G. I. (2010) Lipidinduced insulin resistance: unravelling the mechanism. Lancet, 375, 2267-2277.
157. Protein data bank (PDB). www.pdb.org. 28/02/2011
158. Orellana-Gavalda, J. M.; Herrero, L.; Malandrino, M. I.; Paneda, A.; Sol Rodriguez-Pena, M.; Petry, H.; Asins, G.; Deventer, S. V.; Hegardt, F. G. and Serra, D. (2010) Molecular therapy for obesity and diabetes based on a long-term increase in hepatic fatty-acid oxidation. Hepatology, doi: 10.1002/hep.24140
159. Kuhajda, F. P. and Ronnett, G. V. (2007) Modulation of carnitine palmitoyltransferase-1 for the treatment of obesity. Curr. Opin. Investig. Drugs, 8, 312-317.
160. An, J.; Muoio, D. M.; Shiota, M.; Fujimoto, Y.; Cline, G. W.; Shulman, G. I.; Koves, T. R.; Stevens, R.; Millington, D. and Newgard, C. B. (2004) Hepatic expression of malonyl-CoAdecarboxylase reverses muscle, liver and whole-animal insulin resistance. Nat. Med., 10, 268-274.
161. Towler, M. C. and Hardie, D. G. (2007) AMP-activated protein kinase in metabolic control and insulin signaling. Circ. Res., 100, 328-341.
162. Tsuchida, A.; Yamauchi, T. and Kadowaki, T. (2005) Nuclear receptors as targets for drug development: Molecular mechanisms for regulation of obesity and insulin resistance by peroxisome proliferator-activated receptor gamma, CREB-binding protein, and adiponectin. J. Pharmacol. Sci., 97, 164-170.
163. Blaschke, F.; Takata, Y.; Caglayan, E.; Law, R. E. and Hsueh, W. A. (2006) Obesity, peroxisome proliferator-activated receptor, and atherosclerosis in type 2 diabetes. Arterioscler. Thromb. Vasc. Biol., 26, 28-40.
164. Furuhashi, M. and Hotamisligil, G. S. (2008) Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat. Rev. Drug Discov., 7, 489-503.
165. Halford, J. C. (2001) Pharmacology of appetite suppression: implication for the treatment of obesity. Curr. Drug Targets, 2, 353-370.
166. Castaneda, T. R.; Tong, J.; Datta, R.; Culler, M. and Tschop, M. H. (2010) Ghrelin in the regulation of body weight and metabolism. Front. Neuroendocrinol., 31, 44-60.
167. Reddy, J. K. and Mannaerts, G. P. (1994) Peroxisomal lipid metabolism. Annu. Rev. Nutr., 14, 343-370.
168. Wanders, R. J. (2004) Peroxisomes, lipid metabolism, and peroxisomal disorders. Mol. Genet. Metab., 83, 16-27.
169. Savage, D. B.; Choi, C. S.; Samuel, V. T.; Liu, Z. X.; Zhang, D.; Wang, A.; Zhang, X. M.; Cline, G. W.; Yu, X. X.; Geisler, J. G.; Bhanot, S.; Monia, B. P. and Shulman, G. I. (2006) Reversal of diet-induced hepatic steatosis and hepatic insulin resistance by antisense oligonucleotide inhibitors of acetyl-CoA carboxylases 1 and 2. J. Clin. Invest., 116, 817-824.
170. Miyazaki, M. and Ntambi, J. M. (2003) Role of stearoyl-coenzyme A desaturase in lipid metabolism. Prostaglandins Leukot. Essent. Fatty Acids, 68, 113-121.
171. Biddinger, S. B.; Almind, K.; Miyazaki, M.; Kokkotou, E.; Ntambi, J. M. and Kahn, C. R. (2005) Effects of diet and genetic background on sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase 1, and the development of the metabolic syndrome. Diabetes, 54, 1314-1323.
172. Wright, H. M.; Clish, C. B.; Mikami, T.; Hauser, S.; Yanagi, K.; Hiramatsu, R.; Serhan, C. N. and Spiegelman, B. M. (2000) A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation. J. Biol. Chem., 275, 1873-1877.