Proteomic analysis for antiobesity potential of capsaicin on white adipose tissue in rats fed with a high fat diet

Journal of Proteome Research

Volumn 9, Issue 6, 2010, Pages 2977-2987

  Joo, Jeong In ^a   Kim, Dong Hyun ^a   Choi, Jung Won ^a   Yun, Jong Won ^a  

^a Daegu University   (South Korea)

Author keywords

fatty acid oxidation; obesity; proteomics; thermogenesis; white adipose tissue

Indexed keywords

CAPSAICIN; FLAVOPROTEIN; HEAT SHOCK PROTEIN 27; PEROXIREDOXIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE); SODIUM CHLORIDE; VIMENTIN;

ANIMAL TISSUE; ANTIOBESITY ACTIVITY; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; DOWN REGULATION; DRUG ACTIVITY; ELECTROPHORESIS; HOMOGENATE; LIPID DIET; LIPID METABOLISM; MALE; MASS SPECTROMETRY; NONHUMAN; NUCLEOTIDE SEQUENCE; OBESITY; OLFACTORY RECEPTOR; PRIORITY JOURNAL; PROTEIN ANALYSIS; RAT; THERMOGENESIS; UPREGULATION; WHITE ADIPOSE TISSUE;

ADIPOSE TISSUE, WHITE; ANALYSIS OF VARIANCE; ANIMALS; BLOTTING, WESTERN; CAPSAICIN; DIETARY FATS; ELECTROPHORESIS, GEL, TWO-DIMENSIONAL; FATTY ACIDS; GENE EXPRESSION; MALE; OBESITY; POLYMERASE CHAIN REACTION; PROTEOME; PROTEOMICS; RATS; RATS, SPRAGUE-DAWLEY; REPRODUCIBILITY OF RESULTS; RNA, MESSENGER; THERMOGENESIS; WEIGHT GAIN;

RATTUS;

EID: 77954582014     PISSN: 15353893     EISSN: 15353907     Source Type: Journal    
DOI: 10.1021/pr901175w     Document Type: Article

References (90)

1. Aguilera, C. M.; Gil-Campos, M.; Canete, R.; Gil, A. Alterations in plasma and tissue lipids associated with obesity and metabolic syndrome. Clin. Sci. (London) 2008, 114 (3), 183-193
2. Hotamisligil, G. S. Molecular mechanisms of insulin resistance and the role of the adipocyte. Int. J. Obes. Relat. Metab. Disord. 2000, 24, 23-27
3. Barcelo-Batllori, S.; Corominola, H.; Claret, M.; Canals, I.; Guinovart, J.; Gomis, R. Target identification of the novel antiobesity agent tungstate in adipose tissue from obese rats. Proteomics 2005, 5 (18), 4927-4935
4. Bastard, J. P.; Maachi, M.; Lagathu, C.; Kim, M. J.; Caron, M.; Vidal, H.; Capeau, J.; Feve, B. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur. Cytokine. Network 2006, 17 (1), 4-12.
5. Palomo, I.; Alarcon, M.; Moore-Carrasco, R.; Argiles, J. M. Hemostasis alterations in metabolic syndrome (review). Int. J. Mol. Med. 2006, 18 (5), 969-974
6. Mercader, J.; Ribot, J.; Murano, I.; Felipe, F.; Cinti, S.; Bonet, M. L.; Palou, A. Remodeling of white adipose tissue after retinoic acid administration in mice. Endocrinology 2006, 147 (11), 5325-5332
7. Maeda, H.; Hosokawa, M.; Sashima, T.; Miyashita, K. Dietary combination of fucoxanthin and fish oil attenuates the weight gain of white adipose tissue and decreases blood glucose in obese/diabetic KK-Ay mice. J. Agric. Food Chem. 2007, 55 (19), 7701-7706
8. Walker, C. G.; Zariwala, M. G.; Holness, M. J.; Sugden, M. C. Diet, obesity and diabetes: a current update. Clin. Sci. (London) 2007, 112 (2), 93-111.
9. Backonja, M.; Wallace, M. S.; Blonsky, E. R.; Cutler, B. J.; Malan, P., Jr.; Rauck, R.; Tobias, J. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet Neurol. 2008, 7 (12), 1106-1112
10. Mori, A.; Lehmann, S.; O'Kelly, J.; Kumagai, T.; Desmond, J. C.; Pervan, M.; McBride, W. H.; Kizaki, M.; Koeffler, H. P. Capsaicin, a component of red peppers, inhibits the growth of androgenindependent, p53 mutant prostate cancer cells. Cancer Res. 2006, 66 (6), 3222-3229
11. Chou, C. C.; Wu, Y. C.; Wang, Y. F.; Chou, M. J.; Kuo, S. J.; Chen, D. R. Capsaicin-induced apoptosis in human breast cancer MCF-7 cells through caspase-independent pathway. Oncol. Rep. 2009, 21 (3), 665-671
12. Baek, Y. M.; Hwang, H. J.; Kim, S. W.; Hwang, H. S.; Lee, S. H.; Kim, J. A.; Yun, J. W. A comparative proteomic analysis for capsaicin-induced apoptosis between human hepatocarcinoma (HepG2) and human neuroblastoma (SK-N-SH) cells. Proteomics 2008, 8 (22), 4748-4767
13. Surh, Y. J. Anti-tumor promoting potential of selected spice ingredients with antioxidative and anti-inflammatory activities: a short review. Food Chem. Toxicol. 2002, 40 (8), 1091-1097
14. Reinbach, H. C.; Smeets, A.; Martinussen, T.; Moller, P.; Westerterp-Plantenga, M. S. Effects of capsaicin, green tea and CH-19 sweet pepper on appetite and energy intake in humans in negative and positive energy balance. Clin. Nutr. 2009, 28 (3), 260-265
15. Kawada, T.; Hagihara, K.; Iwai, K. Effects of capsaicin on lipid metabolism in rats fed a high fat diet. J. Nutr. 1986, 116 (7), 1272-1278
16. Caterina, M. J.; Schumacher, M. A.; Tominaga, M.; Rosen, T. A.; Levine, J. D.; Julius, D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997, 389 (6653), 816-824
17. Zhang, L. L.; Yan Liu, D.; Ma, L. Q.; Luo, Z. D.; Cao, T. B.; Zhong, J.; Yan, Z. C.; Wang, L. J.; Zhao, Z. G.; Zhu, S. J.; Schrader, M.; Thilo, F.; Zhu, Z. M.; Tepel, M. Activation of transient receptor potential vanilloid type-1 channel prevents adipogenesis and obesity. Circ. Res. 2007, 100 (7), 1063-1070
18. Kozak, L. P.; Anunciado-Koza, R. UCP1: its involvement and utility in obesity. Int. J. Obes. (Lond). 2008, 32, S32-8.
19. Kontani, Y.; Wang, Y.; Kimura, K.; Inokuma, K. I.; Saito, M.; Suzuki-Miura, T.; Wang, Z.; Sato, Y.; Mori, N.; Yamashita, H. UCP1 deficiency increases susceptibility to diet-induced obesity with age. Aging Cell 2005, 4 (3), 147-155
20. Enerback, S.; Jacobsson, A.; Simpson, E. M.; Guerra, C.; Yamashita, H.; Harper, M. E.; Kozak, L. P. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 1997, 387 (6628), 90-94
21. Liu, X.; Rossmeisl, M.; McClaine, J.; Riachi, M.; Harper, M. E.; Kozak, L. P. Paradoxical resistance to diet-induced obesity in UCP1-deficient mice. J. Clin. Invest. 2003, 111 (3), 399-407.
22. Echtay, K. S.; Roussel, D.; St-Pierre, J.; Jekabsons, M. B.; Cadenas, S.; Stuart, J. A.; Harper, J. A.; Roebuck, S. J.; Morrison, A.; Pickering, S.; Clapham, J. C.; Brand, M. D. Superoxide activates mitochondrial uncoupling proteins. Nature 2002, 415 (6867), 96-99
23. Krauss, S.; Zhang, C. Y.; Lowell, B. B. The mitochondrial uncouplingprotein homologues. Nat. Rev. Mol. Cell Biol. 2005, 6 (3), 248-261
24. Argyropoulos, G.; Harper, M. E. Uncoupling proteins and thermoregulation. J. Appl. Physiol. 2002, 92 (5), 2187-2198
25. Cinti, S. Adipocyte differentiation and transdifferentiation: plasticity of the adipose organ. J. Endocrinol. Invest. 2002, 25 (10), 823-835
26. Oberkofler, H.; Dallinger, G.; Liu, Y. M.; Hell, E.; Krempler, F.; Patsch, W. Uncoupling protein gene: quantification of expression levels in adipose tissues of obese and non-obese humans. J. Lipid Res. 1997, 38 (10), 2125-2133
27. Cabrero, A.; Alegret, M.; Sanchez, R. M.; Adzet, T.; Laguna, J. C.; Vazquez, M. Bezafibrate reduces mRNA levels of adipocyte markers and increases fatty acid oxidation in primary culture of adipocytes. Diabetes 2001, 50 (8), 1883-1890
28. Orci, L.; Cook, W. S.; Ravazzola, M.; Wang, M. Y.; Park, B. H.; Montesano, R.; Unger, R. H. Rapid transformation of white adipocytes into fat-oxidizing machines. Proc. Natl. Acad. Sci. USA 2004, 101 (7), 2058-2063
29. Flachs, P.; Horakova, O.; Brauner, P.; Rossmeisl, M.; Pecina, P.; Franssen-van Hal, N.; Ruzickova, J.; Sponarova, J.; Drahota, Z.; Vlcek, C.; Keijer, J.; Houstek, J.; Kopecky, J. Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce beta-oxidation in white fat. Diabetologia 2005, 48 (11), 2365-2375
30. Kawada, T.; Watanabe, T.; Takaishi, T.; Tanaka, T.; Iwai, K. Capsaicin-induced beta-adrenergic action on energy metabolism in rats: influence of capsaicin on oxygen consumption, the respiratory quotient, and substrate utilization. Proc. Soc. Exp. Biol. Med. 1986, 183 (2), 250-256
31. Watanabe, T.; Kawada, T.; Yamamoto, M.; Iwai, K. Capsaicin, a pungent principle of hot red pepper, evokes catecholamine secretion from the adrenal medulla of anesthetized rats. Biochem. Biophys. Res. Commun. 1987, 142 (1), 259-264
32. Jimenez, M.; Leger, B.; Canola, K.; Lehr, L.; Arboit, P.; Seydoux, J.; Russell, A. P.; Giacobino, J. P.; Muzzin, P.; Preitner, F.-1/-2/-3-adrenoceptor knockout mice are obese and cold-sensitive but have normal lipolytic responses to fasting. FEBS Lett. 2002, 530 (1-3), 37-40.
33. Diepvens, K.; Westerterp, K. R.; Westerterp-Plantenga, M. S. Obesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin, and green tea. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007, 292 (1), R77-85.
34. Bottcher, H.; Furst, P. Decreased white fat cell thermogenesis in obese individuals. Int. J. Obes. Relat. Metab. Disord. 1997, 21 (6), 439-444
35. Semple, R. K.; Crowley, V. C.; Sewter, C. P.; Laudes, M.; Christodoulides, C.; Considine, R. V.; Vidal-Puig, A.; O'Rahilly, S. Expression of the thermogenic nuclear hormone receptor coactivator PGC-1alpha is reduced in the adipose tissue of morbidly obese subjects. Int. J. Obes. Relat. Metab. Disord. 2004, 28 (1), 176-179
36. Yang, X.; Enerback, S.; Smith, U. Reduced expression of FOXC2 and brown adipogenic genes in human subjects with insulin resistance. Obes. Res. 2003, 11 (10), 1182-1191
37. Kumar, S. G.; Rahman, M. A.; Lee, S. H.; Hwang, H. S.; Kim, H. A.; Yun, J. W. Plasma proteome analysis for anti-obesity and antidiabetic potentials of chitosan oligosaccharides in ob/ob mice. Proteomics 2009, 9 (8), 2149-2162
38. Byun, H. O.; Han, N. K.; Lee, H. J.; Kim, K. B.; Ko, Y. G.; Yoon, G.; Lee, Y. S.; Hong, S. I.; Lee, J. S. Cathepsin D and eukaryotic translation elongation factor 1 as promising markers of cellular senescence. Cancer Res. 2009, 69 (11), 4638-4647
39. Schaub, N. P.; Jones, K. J.; Nyalwidhe, J. O.; Cazares, L. H.; Karbassi, I. D.; Semmes, O. J.; Feliberti, E. C.; Perry, R. R.; Drake, R. R. Serum proteomic biomarker discovery reflective of stage and obesity in breast cancer patients. J. Am. Coll. Surg. 2009, 208 (5), 970-978
40. Sharma, A.; Chavali, S.; Mahajan, A.; Tabassum, R.; Banerjee, V.; Tandon, N.; Bharadwaj, D. Genetic association, post-translational modification, and protein-protein interactions in Type 2 diabetes mellitus. Mol. Cell. Proteomics 2005, 4 (8), 1029-1037
41. Park, J. Y.; Seong, J. K.; Paik, Y. K. Proteomic analysis of dietinduced hypercholesterolemic mice. Proteomics 2004, 4 (2), 514-523
42. Veenstra, T. D.; Conrads, T. P.; Hood, B. L.; Avellino, A. M.; Ellenbogen, R. G.; Morrison, R. S. Biomarkers: mining the biofluid proteome. Mol. Cell. Proteomics 2005, 4 (4), 409-418
43. Hanash, S. Disease proteomics. Nature 2003, 422 (6928), 226-232
44. Shevchenko, A.; Tomas, H.; Havlis, J.; Olsen, J. V.; Mann, M. Ingel digestion for mass spectrometric characterization of proteins and proteomes. Nat. Protoc. 2006, 1 (6), 2856-2860
45. Kim, S. W.; Hwang, H. J.; Cho, E. J.; Oh, J. Y.; Baek, Y. M.; Choi, J. W.; Yun, J. W. Time-dependent plasma protein changes in streptozotocin-induced diabetic rats before and after fungal polysaccharide treatments. J. Proteome Res. 2006, 5 (11), 2966-2976
46. Yang, Y.; Shang, W.; Zhou, L.; Jiang, B.; Jin, H.; Chen, M. Emodin with PPARgamma ligand-binding activity promotes adipocyte differentiation and increases glucose uptake in 3T3-Ll cells. Biochem. Biophys. Res. Commun. 2007, 353 (2), 225-230
47. DeLany, J. P.; Floyd, Z. E.; Zvonic, S.; Smith, A.; Gravois, A.; Reiners, E.; Wu, X.; Kilroy, G.; Lefevre, M.; Gimble, J. M. Proteomic analysis of primary cultures of human adipose-derived stem cells: modulation by Adipogenesis. Mol. Cell. Proteomics 2005, 4 (6), 731-740
48. Kaplan, M. L.; Leveille, G. A. Development of lipogenesis and insulin sensitivity in tissues of the ob/ob mouse. Am. J. Physiol. 1981, 240 (2), 101-107
49. Gaikwad, A.; Long, D. J., 2nd; Stringer, J. L.; Jaiswal, A. K. In vivo role of NAD(P)H:quinone oxidoreductase 1 (NQO1) in the regulation of intracellular redox state and accumulation of abdominal adipose tissue. J. Biol. Chem. 2001, 276 (25), 22559-22564
50. Martin, L. F.; Patrick, S. D.; Wallin, R. DT-diaphorase in morbidly obese patients. Cancer Lett. 1987, 36 (3), 341-347
51. Siegel, D.; Franklin, W. A.; Ross, D. Immunohistochemical detection of NAD(P)H:quinone oxidoreductase in human lung and lung tumors. Clin. Cancer Res. 1998, 4 (9), 2065-2070
52. Lieber, J. G.; Evans, R. M. Disruption of the vimentin intermediate filament system during adipose conversion of 3T3-L1 cells inhibits lipid droplet accumulation. J. Cell Sci. 1996, 109 (13), 3047-3058
53. Franke, W. W.; Hergt, M.; Grund, C. Rearrangement of the vimentin cytoskeleton during adipose conversion: formation of an intermediate filament cage around lipid globules. Cell 1987, 49 (1), 131-141
54. Young, J. C.; Agashe, V. R.; Siegers, K.; Hartl, F. U. Pathways of chaperone-mediated protein folding in the cytosol. Nat. Rev. Mol. Cell Biol. 2004, 5 (10), 781-791
55. Cherian, M.; Abraham, E. C. Diabetes affects alpha-Crystallin chaperone function. Biochem. Biophys. Res. Commun. 1995, 212 (1), 184-189
56. Kumar, M. S.; Reddy, P. Y.; Kumar, P A.; Surolia, I.; Reddy, G. B. Effect of dicarbonyl-induced browning on alpha-Crystallin chaperone-like activity: physiological significance and caveats of in vitro aggregation assays. Biochem. J. 2004, 379 (2), 273-282
57. Kurucz, I.; Morva, A.; Vaag, A.; Eriksson, K. F.; Huang, X.; Groop, L.; Koranyi, L. Decreased expression of heat shock protein 72 in skeletal muscle of patients with type 2 diabetes correlates with insulin resistance. Diabetes 2002, 51 (4), 1102-1109
58. Yeh, W. C.; Li, T. K.; Bierer, B. E.; McKnight, S. L. Identification and characterization of an immunophilin expressed during the clonal expansion phase of adipocyte differentiation. Proc. Natl. Acad. Sci. USA 1995, 92 (24), 11081-11085
59. Bohren, K. M.; Bullock, B.; Wermuth, B.; Gabbay, K. H. The aldoketo reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases. J. Biol. Chem. 1989, 264 (16), 9547-9551
60. Donaghue, K. C.; Margan, S. H.; Chan, A. K.; Holloway, B.; Silink, M.; Rangel, T.; Bennetts, B. The association of aldose reductase gene (AKR1B1) polymorphisms with diabetic neuropathy in adolescents. Diabet. Med. 2005, 22 (10), 1315-1320
61. Tirard, J.; Gout, J.; Lefrancois-Martinez, A. M.; Martinez, A.; Begeot, M.; Naville, D. A novel inhibitory protein in adipose tissue, the aldo-keto reductase AKR1B7: its role in adipogenesis. Endocrinology 2007, 148 (5), 1996-2005.
62. Kang, S. W.; Chae, H. Z.; Seo, M. S.; Kim, K.; Baines, I. C.; Rhee, S. G. Mammalian peroxiredoxin isoforms can reduce hydrogen peroxide generated in response to growth factors and tumor necrosis factor-alpha. J. Biol. Chem. 1998, 273 (11), 6297-6302
63. Cha, M. K.; Suh, K. H.; Kim, I. H. Overexpression of peroxiredoxin I and thioredoxin1 in human breast carcinoma. J. Exp. Clin. Cancer Res. 2009, 28, 93.
64. Chae, H. Z.; Robison, K.; Poole, L. B.; Church, G.; Storz, G.; Rhee, S. G. Cloning and sequencing of thiol-specific antioxidant from mammalian brain: alkyl hydroperoxide reductase and thiol-specific antioxidant define a large family of antioxidant enzymes. Proc. Natl. Acad. Sci. USA 1994, 91 (15), 7017-7021
65. Matejkova, O.; Mustard, K. J.; Sponarova, J.; Flachs, P.; Rossmeisl, M.; Miksik, I.; Thomason-Hughes, M.; Grahame Hardie, D.; Kopecky, J. Possible involvement of AMP-activated protein kinase in obesity resistance induced by respiratory uncoupling in white fat. FEBS Lett. 2004, 569 (1-3), 245-248
66. Daval, M.; Foufelle, F.; Ferre, P. Functions of AMP-activated protein kinase in adipose tissue. J. Physiol. 2006, 574 (1), 55-62.
67. Rossmeisl, M.; Barbatelli, G.; Flachs, P.; Brauner, P.; Zingaretti, M. C.; Marelli, M.; Janovska, P.; Horakova, M.; Syrovy, I.; Cinti, S.; Kopecky, J. Expression of the uncoupling protein 1 from the aP2 gene promoter stimulates mitochondrial biogenesis in unilocular adipocytes in vivo. Eur. J. Biochem. 2002, 269 (1), 19-28.
68. Prpic, V.; Watson, P. M.; Frampton, I. C.; Sabol, M. A.; Jezek, G. E.; Gettys, T. W. Adaptive changes in adipocyte gene expression differ in AKR/J and SWR/J mice during diet-induced obesity. J. Nutr. 2002, 132 (11), 3325-3332
69. Surwit, R. S.; Wang, S.; Petro, A. E.; Sanchis, D.; Raimbault, S.; Ricquier, D.; Collins, S. Diet-induced changes in uncoupling proteins in obesity-prone and obesity-resistant strains of mice. Proc. Natl. Acad. Sci. USA 1998, 95 (7), 4061-4065
70. Watson, P. M.; Commins, S. P.; Beiler, R. J.; Hatcher, H. C.; Gettys, T. W. Differential regulation of leptin expression and function in A/J vs. Am. J. Physiol. Endocrinol. Metab. 2000, 279 (2), E356-65.
71. Tiraby, C.; Tavernier, G.; Lefort, C.; Larrouy, D.; Bouillaud, F.; Ricquier, D.; Langin, D. Acquirement of brown fat cell features by human white adipocytes. J. Biol. Chem. 2003, 278 (35), 33370-33376
72. Spiegelman, B. M.; Puigserver, P.; Wu, Z. Regulation of adipogenesis and energy balance by PPARgamma and PGC-1. Int. J. Obes. Relat. Metab. Disord. 2000, 24, S8-10.
73. Puigserver, P.; Picó, C.; Stock, M. J.; Palou, A. Effect of selective beta-adrenoceptor stimulation on UCP synthesis in primary cultures of brown adipocytes. Mol. Cell. Endocrinol. 1996, 117 (1), 7-16.
74. Kobayashi, A.; Osaka, T.; Namba, Y.; Inoue, S.; Lee, T. H.; Kimura, S. Capsaicin activates heat loss and heat production simultaneously and independently in rats. Am. J. Physiol. 1998, 275 (1-2), 92-98
75. Masuda, Y.; Haramizu, S.; Oki, K.; Ohnuki, K.; Watanabe, T.; Yazawa, S.; Kawada, T.; Hashizume, S.; Fushiki, T. Upregulation of uncoupling proteins by oral administration of capsiate, a nonpungent capsaicin analog. J. Appl. Physiol. 2003, 95 (6), 2408-2415
76. Osaka, T.; Kobayashi, A.; Namba, Y.; Ezaki, O.; Inoue, S.; Kimura, S.; Lee, T. H. Temperature-and capsaicin-sensitive nerve fibers in brown adipose tissue attenuate thermogenesis in the rat. Pflugers Arch. 1998, 437 (1), 36-42.
77. Giordano, A.; Morroni, M.; Carle, F.; Gesuita, R.; Marchesi, G. F.; Cinti, S. Sensory nerves affect the recruitment and differentiation of rat periovarian brown adipocytes during cold acclimation. J. Cell Sci. 1998, 111 (17), 2587-2594
78. Fleury, C.; Neverova, M.; Collins, S.; Raimbault, S.; Champigny, O.; Levi-Meyrueis, C.; Bouillaud, F.; Seldin, M. F.; Surwit, R. S.; Ricquier, D.; Warden, C. H. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat. Genet. 1997, 15 (3), 269-272
79. Arsenijevic, D.; Onuma, H.; Pecqueur, C.; Raimbault, S.; Manning, B. S.; Miroux, B.; Couplan, E.; Alves-Guerra, M. C.; Goubern, M.; Surwit, R.; Bouillaud, F.; Richard, D.; Collins, S.; Ricquier, D. Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat. Genet. 2000, 26 (4), 435-439
80. Negre-Salvayre, A.; Hirtz, C.; Carrera, G.; Cazenave, R.; Troly, M.; Salvayre, R.; Penicaud, L.; Casteilla, L. A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation. FASEB J. 1997, 11 (10), 809-815
81. Blanc, J.; Alves-Guerra, M. C.; Esposito, B.; Rousset, S.; Gourdy, P.; Ricquier, D.; Tedgui, A.; Miroux, B.; Mallat, Z. Protective role of uncoupling protein 2 in atherosclerosis. Circulation 2003, 107 (3), 388-390
82. Duval, C.; Negre-Salvayre, A.; Dogilo, A.; Salvayre, R.; Penicaud, L.; Casteilla, L. Increased reactive oxygen species production with antisense oligonucleotides directed against uncoupling protein 2 in murine endothelial cells. Biochem. Cell Biol. 2002, 80 (6), 757-764 (Pubitemid 37330242)
83. Mattiasson, G.; Shamloo, M.; Gido, G.; Mathi, K.; Tomasevic, G.; Yi, S.; Warden, C. H.; Castilho, R. F.; Melcher, T.; Gonzalez-Zulueta, M.; Nikolich, K.; Wieloch, T. Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma. Nat. Med. 2003, 9 (8), 1062-1068
84. Farmer, S. R. Transcriptional control of adipocyte formation. Cell Metab. 2006, 4 (4), 263-273
85. Zhang, Y.; Proenca, R.; Maffei, M.; Barone, M.; Leopold, L.; Friedman, J. M. Positional cloning of the mouse obese gene and its human homologue. Nature 1994, 372 (6505), 425-432
86. Margetic, S.; Gazzola, C.; Pegg, G. G.; Hill, R. A. Leptin: a review of its peripheral actions and interactions. Int. J. Obes. Relat. Metab. Disord. 2002, 26 (11), 1407-1433
87. Seufert, J. Leptin effects on pancreatic beta-cell gene expression and function. Diabetes 2004, 53, 152-158
88. Cawthorn, W. P.; Sethi, J. K. TNF-alpha and adipocyte biology. FEBS. Lett. 2008, 582 (1), 117-131
89. Hotamisligil, G. S.; Shargill, N. S.; Spiegelman, B. M. Adipose expression of tumor necrosis factor-alpha: direct role in obesitylinked insulin resistance. Science 1993, 259 (5091), 87-91.
90. Hotamisligil, G. S.; Arner, P.; Caro, J. F.; Atkinson, R. L.; Spiegelman, B. M. Increased adipose tissue expression of tumor necrosis factoralpha in human obesity and insulin resistance. J. Clin. Invest. 1995, 95 (5), 2409-2415