The role of peroxisome proliferator-activated receptors γ (PPARγ) in obesity and insulin resistance;Rola receptorów aktywowanych przez proliferatory peroksysomów γ (PPARγ) w otyłości i insulinooporności

Postepy Higieny i Medycyny Doswiadczalnej

Volumn 67, Issue , 2013, Pages 1283-1299

  Chmielewska Kassassir, Małgorzata ^a   Woźniak, Lucyna A ^a   Ogrodniczek, Paweł ^a   Wójcik, Marzena ^a  

^a MEDICAL UNIVERSITY OF LODZ   (Poland)

Author keywords

Adipogenesis; Diabetes mellitus 2 (T2DM); Insulin resistance; Obesity; Peroxisome proliferator activated receptors gamma (PPAR ); Thiazolidinediones (TZDs)

Indexed keywords

ADIPOCYTOKINE; CELL RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; TRANSCRIPTION FACTOR;

ADIPOSE TISSUE; ARTICLE; HUMAN; HYPERTENSION; INFLAMMATION; INSULIN RESISTANCE; METABOLIC SYNDROME X; METABOLISM; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PHYSIOLOGY;

ADIPOKINES; ADIPOSE TISSUE; DIABETES MELLITUS, TYPE 2; HUMANS; HYPERTENSION; INFLAMMATION; INSULIN RESISTANCE; METABOLIC SYNDROME X; OBESITY; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; PPAR GAMMA; RECEPTORS, CYTOPLASMIC AND NUCLEAR; TRANSCRIPTION FACTORS;

EID: 84892589901     PISSN: 00325449     EISSN: 17322693     Source Type: Journal    
DOI: 10.5604/17322693.1080028     Document Type: Article

References (130)

1. Abella A., Dubus P., Malumbres M., Rane S. G., Kiyokawa H., Sicard A., Vignon F., Langin D., Barbacid M., Fajas L.: Cdk4 promotes adipogenesis through PPARγ activation. Cell Metab., 2005;2:239-249
2. Agostini M., Schoenmakers E., Mitchell C., Szatmari I., Savage D., Smith A., Rajanayagam O., Semple R., Luan J., Bath L., Zalin A., Labib M., Kumar S., Simpson H., Blom D. i wsp.: Non-DNA binding, dominant-negative, human PPARγ mutations cause lipodystrophic insulin resistance. Cell Metab., 2006;4:303-311
3. Altshuler D., Hirschhorn J. N., Klannemark M., Lindgren C. M., Vohl M. C., Nemesh J., Lane C. D., Schaffner S. F., Bolk A., Brewer C., Tuomi T., Gaudet D., Hudson T. J., Daly M., Groop L., Lander E. S.: The common PPARg Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat. Gen., 2000;26:76-80
4. Armoni M., Kritz N., Harel C., Bar-Yoseph F., Chen H., Quon M. J., Karnieli E.: Peroxisome proliferator-activated receptor-gamma represses GLUT4 promoter activity in primary adipocytes, and rosiglitazone alleviates this effect. J. Biol. Chem., 2003;278:30614-30623
5. Balakumar P., Rose M., Ganti S. S., Krishan P., Singh M.: PPAR dual agonists: are they opening Pandora's Box? Pharmacol. Res., 2007;56:91-98
6. Barroso I., Gurnell M., Crowley V. E., Agostini M., Schwabe J. W., Soos M. A., Maslen G. L., Williams T. D., Lewis H., Schafer A. J., Chatterjee V. K., O'Rahilly S.: Dominant negative mutations in human PPAR-gamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature, 1999;402:880-883
7. 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 Netw.: 2006;17:4-12
8. Berger J., Tanen M., Elbrecht A., Hermanowski-Vosatka A., Moller D. E., Wright S. D., Thieringer R.: Peroxisome proliferator-activated receptor-gamma ligands inhibit adipocyte 11β-hydroxysteroid dehydrogenase type 1 expression and activity. J. Biol. Chem., 2001;276:12629-12635
9. Biela U., Pajak A., Kaczmarczyk-Chałas K., Głuszek J., Tendera M., Waśkiewicz A., Kurjata P., Wyrzykowski B.: Incidence of overweight and obesity in women and men between the ages of 20-74. Results of the WOBASZ program. Kardiol. Pol., 2005;63(Suppl. 4):S632-S635
10. Bokarewa M., Nagaev I., Dahlberg L., Smith U., Tarkowski A.: Resistin, an adipokine with potent proinflammatory properties. J. Immunol., 2005;174:5789-5795
11. Brown K. K., Henke B. R., Blanchard S. G., Cobb J. E., Mook R., Kaldor I., Kliewer S. A., Lehmann J. M., Lenhard J. M., Harrington W. W., Novak P. J., Faison W., Binz J. G., Hashim M. A., Oliver W. O. i wsp.: A novel N-aryl tyrosine activator of peroxisome proliferator-activated receptor-gamma reverses the diabetic phenotype of the Zucker diabetic fatty rat. Diabetes, 1999;48:1415-1424
12. Buse J. B., Rubin C. J., Frederich R., Viraswami-Appanna K., Lin K. C., Montoro R., Shockey G., Davidson J. A.: Muraglitazar, a dual (α/γ) PPAR activator: a randomized, double-blind, placebo-controlled, 24-week monotherapy trial in adult patients with type 2 diabetes. Clin. Ther., 2005;27:1181-1195
13. Chawla A., Schwarz E. J., Dimaculangan D. D., Lazar M. A.: Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology, 1994;135:798-800
14. Cheatham W. W.: Peroxisome proliferator-activated receptor translational research and clinical experience. Am. J. Clin. Nutr., 2010;91:S262-S266
15. Chu J. W., Abbasi F., Lamendola C., McLaughlin T., Reaven G. M., Tsao P. S.: Effect of rosiglitazone treatment on circulating vascular and inflammatory markers ininsulin-resistant subjects. Diab. Vasc. Dis. Res., 2005;2:37-41
16. Costa V., Casamassimi A., Esposito K., Villani A., Capone M., Iannella R., Schisano B., Ciotola M., Di Palo C., Corrado F. C., Santangelo F., Giugliano D., Ciccodicola A.: Characterization of a novel polymorphism in PPARG regulatory region associated with type 2 diabetes and diabetic retinopathy in Italy. J. Biomed. Biotechnol., 2009;2009:126917
17. Couillard C., Mauriege P., Imbeault P., Prud'homme D., Nadeau A., Tremblay A., Bouchard C., Despres J. P.: Hyperleptinemia is more closely associated with adipose cell hypertrophy than with adipose tissue hyperplasia. Int. J. Obes., 2000;24:782-788
18. Dalen K. T., Schoonjans K., Ulven S. M., Weedon-Fekjaer M. S., Bentzen T. G., Koutnikova H., Auwerx J., Nebb H. I.: Adipose tissue expression of the lipid droplet-associating proteins S3-12 and perilipinis controlled by peroxisome proliferator-activated receptor-γ. Diabetes, 2004;53:1243-1252
19. De Vos P., Lefebvre A. M., Miller S. G., Guerre-Millo M., Wong K., Saladin R., Hamann L. G., Staels B., Briggs M. R., Auwerx J.: Thiazolidinediones repress ob gene expression in rodents via activation of peroxisome proliferator-activated receptor gamma. J. Clin. Invest., 1996;98:1004-1009
20. Deeb S. S., Fajas L., Nemoto M., Pihlajamäki J., Mykkänen L., Kuusisto J., Laakso M., Fujimoto W., Auwerx J.: A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat. Genet., 1998;20:284-287
21. Doney A. S., Fischer B., Cecil J. E., Boylan K., McGuigan F. E., Ralston S. H., Morris A. D., Palmer C. N.: Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes with susceptibility to Type 2 diabetes. Diabetologia, 2004;47:555-558
22. Ek J., Andersen G., Urhammer S. A., Hansen L., Carstensen B., Borch-Johnsen K., Drivsholm T., Berglund L., Hansen T., Lithell H., Pedersen O.: Studies of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-g2 (PPAR-g2) gene in relation to insulin sensitivity among glucose tolerant Caucasians. Diabetologia, 2001;44:1170-1176
23. Fajas L., Auboeuf D., Raspé E., Schoonjans K., Lefebvre A. M., Saladin R., Najib J., Laville M., Fruchart J. C., Deeb S., Vidal-Puig A., Flier J., Briggs M. R., Staels B., Vidal H., Auwerx J.: The organization, promoter analysis, and expression of the human PPAR-gamma gene. J. Biol. Chem., 1997;272:18779-18789
24. Fasshauer M., Kralisch S., Klier M., Lossner U., Bluher M., Klein J, Paschke R.: Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem. Biophys. Res. Commun., 2003;301:1045-1050
25. Feige J. N., Gelman L., Michalik L., Desvergne B., Wahli W.: From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. Prog. Lipid Res., 2006;45:120-159
26. Festa A., D'Agostino R. Jr., Tracy R. P., Haffner S. M.: Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes, 2002;51:1131-1137
27. Fiévet C., Fruchart J. C., Staels B.: PPARα and PPARγ dual agonists for the treatment of type 2 diabetes and the metabolic syndrome. Curr. Opin. Pharmacol., 2006;6:606-614
28. Frohnert B. I., Hui T. Y., Bernlohr D. A.: Identification of a functional peroxisome proliferator-responsive element in the murine fatty acid transport protein gene. J. Biol. Chem., 1999;274:3970-3977
29. Furuta M., Yano Y., Gabazza E. C., Araki-Sasaki R., Tanaka T., Katsuki A., Hori Y., Nakatani K., Sumida Y., Adachi Y.: Troglitazone improves GLUT4 expression in adipose tissue in an animal model of obese type 2 diabetes mellitus. Diabetes Res. Clin. Pract., 2002;56:159-171
30. Gathercole L. L., Morgan S. A., Bujalska I. J., Hauton D., Stewart P. M., Tomlinson J. W.: Regulation of lipogenesis by glucocorticoids and insulin in human adipose tissue. PLoS One, 2011;6:e26223
31. Ge K., Guermah M., Yuan C. X., Ito M., Wallberg A. E., Spiegelman B. M., Roeder R. G.: Transcription coactivator TRAP220 is required for PPAR gamma 2-stimulated adipogenesis. Nature, 2002;417:563-567
32. Gogga P., Karbowska J., Meissner W., Kochan Z.: Role of leptin in the regulation of lipid and carbohydrate metabolism. Postȩpy Hig. Med. Dośw., 2011;65:255-262
33. Gonzalez I. C., Lamar J., Iradier F., Xu Y., Winneroski L. L., York J., Yumibe N., Zink R., Montrose-Rafizadeh C., Etgen G. J., Broderick C. L., Oldham B. A., Mantlo N.: Design and synthesis of a novel class of dual PPARgamma/delta agonists. Bioorg. Med. Chem. Lett., 2007;17:1052-1055
34. Gottschling-Zeller H., Röhrig K., Hauner H.: Troglitazone reduces plasminogen activator inhibitor-1 expression and secretion in cultured human adipocytes. Diabetologia, 2000;43:377-383
35. Gouda H. N., Sagoo G. S., Harding A. H., Yates J., Sandhu M. S., Higgins J. P.: The association between the peroxisome proliferator-activated receptor-γ2 (PPARG2) Pro12Ala gene variant and type 2 diabetes mellitus: a HuGE review and meta-analysis. Am. J. Epidemiol., 2010;171:645-655
36. Guan H. P., Ishizuka T., Chui P. C., Lehrke M., Lazar M. A.: Corepressors selectively control the transcriptional activity of PPARγ in adipocytes. Genes Dev., 2005;19:453-461
37. Guan H. P., Li Y., Jensen M. V., Newgard C. B., Steppan C. M., Lazar M. A.: A futile metabolic cycle activated in adipocytes by antidiabetic agents. Nat. Med., 2002;8:1122-1128
38. Haffner S. M., Greenberg A. S., Weston W. M., Chen H., Williams K., Freed M. I.: Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation, 2002;106:679-684
39. Harte A. L., McTernan P. G., McTernan C. L., Smith S. A., Barnett A. H., Kumar S.: Rosiglitazone inhibits the insulin-mediated increase in PAI-1 secretion in human abdominal subcutaneous adipocytes. Diabetes Obes. Metab., 2003;5:302-310
40. Haseeb A., Iliyas M., Chakrabarti S., Farooqui A. A., Naik S. R., Ghosh S., Suragani M., Ehtesham N. Z.: Single-nucleotide polymorphisms in peroxisome proliferator-activated receptor γ and their association with plasma levels of resistin and the metabolic syndrome in a South Indian population. J. Biosci., 2009;34:405-414
41. He Y., Chen H., Quon M. J., Reitman M.: The mouse obese gene. Genomic organization, promoter activity, and activation by CCAAT/enhancer-binding protein α. J. Biol. Chem., 1995;270:28887-28891
42. Heinlein C. A., Ting H. J., Yeh S., Chang C.: Identification of ARA70 as a ligand-enhanced coactivator for the peroxisome proliferator-activated receptor γ. J. Biol. Chem., 1999;274:16147-16152
43. Higgins L. S., Depaoli A. M.: Selective peroxisome proliferator-activated receptor γ (PPARγ) modulation as a strategy for safer therapeutic PPARγ activation. Am. J. Clin. Nutr., 2010;91:S267-S272
44. Hollenberg A. N., Susulic V. S., Madura J. P., Zhang B., Moller D. E., Tontonoz P., Sarraf P., Spiegelman B. M., Lowell B. B.: Functional antagonism between CCAAT/Enhancer binding protein-α and peroxisome proliferator-activated receptor-γ on the leptin promoter. J. Biol. Chem., 1997;272:5283-5290
45. Hotamisligil G. S., Arner P., Caro J. F., Atkinson R. L., Spiegelman B. M.: Increased adipose tissue expression of tumor necrosis factor-α in human obesity and insulin resistance. J. Clin. Invest., 1995;95:2409-2415
46. Hotamisligil G. S., Murray D. L., Choy L. N., Spiegelman B. M.: Tumor necrosis factor α inhibits signaling from the insulin receptor. Proc. Natl. Acad. Sci. USA, 1994:91, 4854-4858
47. Iwaki M., Matsuda M., Maeda N., Funahashi T., Matsuzawa Y., Makishima M., Shimomura I.: Induction of adiponectin, a fat-derivedantidiabetic and antiatherogenicfactor, by nuclear receptors. Diabetes, 2003;52:1655-1663
48. James W. P.: The epidemiology of obesity: the size of the problem. J. Intern. Med., 2008;263:336-352
49. Jiang G., Dallas-Yang Q., Li Z., Szalkowski D., Liu F., Shen X., Wu M., Zhou G., Doebber T., Berger J., Moller D. E., Zhang B. B.: Potentiation of insulin signaling in tissues of Zucker obese rats after acute and long-term treatment with PPARgamma agonists. Diabetes, 2002;51:2412-2419
50. Kahn B. B., Flier J. S.: Obesity and insulin resistance. J. Clin. Invest., 2000;106:473-481
51. Kallen C. B., Lazar M. A.: Antidiabetic thiazolidinediones inhibit leptin (ob) gene expression in 3T3-L1 adipocytes. Proc. Natl. Acad. Sci. USA, 1996;93:5793-5796
52. Kaser S., Kaser A., Sandhofer A., Ebenbichler C. F., Tilg H., Patsch J. R.: Resistin messenger-RNA expression is increased by proinflammatory cytokines in vitro. Biochem. Biophys. Res. Commun., 2003;309:286-290
53. Katsuki A., Sumida Y., Murata K., Furuta M., Araki-Sasaki R., Tsuchihashi K., Hori Y., Yano Y., Gabazza E. C., Adachi Y.: Troglitazone reduces plasma levels of tumour necrosis factor-alpha in obese patients with type 2 diabetes. Diabetes Obes. Metab., 2000;2:189-191
54. Kendall D. M., Rubin C. J., Mohideen P., Ledeine J. M., Belder R., Gross J., Norwood P., O'Mahony M., Sall K., Sloan G., Roberts A., Fiedorek F. T., DeFronzo R. A.: Improvement of glycemic control, triglycerides, and HDL cholesterol levels with muraglitazar, a dual (alpha/gamma) peroxisome proliferator-activated receptor activator, in patients with type 2 diabetes inadequately controlled with metformin monotherapy: A double-blind, randomized, pioglitazone-comparative study. Diabetes Care, 2006;29:1016-1023
55. Kern P. A., Di Gregorio G. B., Lu T., Rassouli N., Ranganathan G.: Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-α expression. Diabetes, 2003;52:1779-1785
56. Kern P. A., Ranganathan S., Li C., Wood L., Ranganathan G.: Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am. J. Physiol. Endocrinol. Metab., 2001;280:E745-E751
57. Kern P. A., Saghizadeh M., Ong J. M., Bosch R. J., Deem R., Simsolo R. B.: The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J. Clin. Invest., 1995;95:2111-2119
58. Kliewer S. A., Lenhard J. M., Willson T. M., Patel I., Morris D. C., Lehmann J. M.: A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation. Cell, 1995;83:813-819
59. Klimcakova E., Kovacikova M., Stich V., Langin D.: Adipokines and dietary interventions in human obesity. Obes. Rev., 2010;11:446-456
60. Kralisch S., Klein J., Lossner U., Blüher M., Paschke R., Stumvoll M., Fasshauer M.: Plasminogen activator inhibitor-1 expression and secretion are stimulated by growth hormone and interleukin-6 in 3T3-L1 adipocytes. Mol. Cell Endocrinol., 2006;253:56-62
61. Kubota N., Terauchi Y., Kubota T., Kumagai H., Itoh S., Satoh H., Yano W., Ogata H., Tokuyama K., Takamoto I., Mineyama T., Ishikawa M., Moroi M., Sugi K., Yamauchi T., Ueki K., Tobe K., Noda T., Nagai R., Kadowaki T.: Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin-dependent and - independent pathways. J. Biol. Chem., 2006;281:8748-8755
62. Lagathu C., Bastard J. P., Auclair M., Maachi M., Capeau J., Caron M.: Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte: prevention by rosiglitazone. Biochem. Biophys. Res. Commun., 2003;311:372-379
63. Lefebvre P., Chinetti G., Fruchart J. C., Staels B.: Sorting out the roles of PPARα in energy metabolism and vascular homeostasis. J. Clin. Invest., 2006;116:571-580
64. Lehrke M., Lazar M. A.: The many faces of PPARγ. Cell, 2005;123:993-999
65. Li A. C., Brown K. K., Silvestre M. J., Willson T. M., Palinski W., Glass C. K.: Peroxisome proliferator-activated receptor gamma ligands inhibits development of atherosclerosis in LDL receptor-deficient mice. J. Clin. Invest., 2000;106:523-531
66. Li F. P., He J., Li Z. Z., Luo Z. F., Yan L., Li Y.: Effects of resistin expression on glucose metabolism and hepatic insulin resistance. Endocrine, 2009;35:243-251
67. Liu J., DeYoung S. M., Hwang J. B., O'Leary E. E., Saltiel A. R.: The roles of Cbl-b and c-Cbl in insulin-stimulated glucose transport. J. Biol. Chem., 2003;278:36754-36762
68. Luan J., Browne P. O., Harding A. H., Halsall D. J., O'Rahilly S., Chatterjee V. K., Wareham N. J.: Evidence for gene-nutrient interaction at the PPARgamma locus. Diabetes, 2001;50:686-689
69. Lundgren M., Burén J., Ruge T., Myrnäs T., Eriksson J. W.: Glucocorticoids down-regulateglucose uptake capacity and insulin-signaling proteins in omental but not subcutaneous human adipocytes. J. Clin. Endocrinol. Metab., 2004;89:2989-2997
70. Maeda N., Takahashi M., Funahashi T., Kihara S., Nishizawa H., Kishida K., Nagaretani H., Matsuda M., Komuro R., Ouchi N., Kuriyama H., Hotta K., Nakamura T., Shimomura I., Matsuzawa Y.: PPAR-gamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes, 2001;50:2094-2099
71. Martin G., Schoonjans K., Lefebvre A. M., Staels B., Auwerx J.: Coordinate regulation of the expression of the fatty acid transport protein and acyl-CoA synthetase genes by PPARalpha and PPARgamma activators. J. Biol. Chem., 1997;272:28210-28217
72. Masud S., Ye S.: Effect of the peroxisome proliferator activated receptor-gamma gene Pro12Ala variant on body mass index: a meta-analysis. J. Med. Genet., 2003;40:773-780
73. Mukherjee R., Davies P. J., Crombie D. L., Bischoff E. D., Cesario R. M., Jow L., Hamann L. G., Boehm M. F., Mondon C. E., Nadzan A. M., Paterniti J. R. Jr, Heyman R. A.: Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists. Nature, 1997;386:407-410
74. Müller G., Ertl J., Gerl M., Preibisch G.: Leptin impairs metabolic actions of insulin in isolated rat adipocytes. J. Biol. Chem., 1997;272:10585-10593
75. Murakami K., Tobe K., Ide T., Mochizuki T., Ohashi M., Akanuma Y., Yazaki Y., Kadowaki T.: A novel insulin sensitizer acts as a coligand for peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and PPAR-gamma: effect of PPAR-alpha activation on abnormal lipid metabolism in liver of Zucker fatty rats. Diabetes, 1998;47:1841-1847
76. Nissen S. E., Wolski K., Topol E. J.: Effect of muraglitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus. JAMA, 2005;294:2581-2586
77. Okuno A., Tamemoto H., Tobe K., Ueki K., Mori Y., Iwamoto K., Umesono K., Akanuma Y., Fujiwara T., Horikoshi H., Yazaki Y., Kadowaki T.: Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J. Clin. Invest., 1998;101:1354-1361
78. Patel L., Buckels A. C., Kinghorn I. J., Murdock P. R., Holbrook J. D., Plumpton C., Macphee C. H., Smith S. A.: Resistin is expressed in human macrophages and directly regulated by PPARγ activators. Biochem. Biophys. Res. Commun., 2003;300:472-476
79. Peraldi P., Xu M., Spiegelman B. M.: Thiazolidinediones block tumor necrosis factor-α-induced inhibition of insulin signaling. J. Clin. Invest., 1997;100:1863-1869
80. Renaud J. P., Moras D.: Structural studies on nuclear receptors. Cell Mol. Life Sci., 2000;57:1748-1769
81. Report of a WHO Consultation on Obesity. Preventing and Managing the Global Epidemic. Division of noncomunicable Diseases. World Health Organization. Geneva 3-5 June 1997. WHO/NUT/NCD 1998
82. Rhee E. J., Oh K. W., Lee W. Y., Kim S. Y., Oh E. S., Baek K. H., Kang M. I., Kim S. W.: Effects of two common polymorphisms of peroxisome proliferator-activated receptor-γ gene on metabolic syndrome. Arch. Med. Res., 2006;37:86-94
83. Ristow M., Müller-Wieland D., Pfeiffer A., Krone W., Kahn C. R.: Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. N. Engl. J. Med., 1998;339:953-959
84. Rosen E. D., Sarraf P., Troy A. E., Bradwin G., Moore K., Milstone D. S., Spiegelman B. M., Mortensen R. M.: PPARγ is required for the differentiation of adipose tissue in vivo and in vitro. Mol. Cell, 1999;4:611-617
85. Rosen E. D., Walkey C. J., Puigserver P., Spiegelman B. M.: Transcriptional regulation of adipogenesis. Genes Dev., 2000;14:1293-1307
86. Rotter V., Nagaev I., Smith U.: Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-α, overexpressed in human fat cells from insulin-resistant subjects. J. Biol. Chem., 2003;278:45777-45784
87. Ruan H., Hacohen N., Golub T. R., Van Parijs L., Lodish H. F.: Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-κB activation by TNF-α is obligatory. Diabetes, 2002;51:1319-1336
88. Ruan H., Pownall H. J., Lodish H. F.: Troglitazone antagonizes tumor necrosis factor-α-induced reprogramming of adipocyte gene expression by inhibiting the transcriptional regulatory functions of NF-κB. J. Biol. Chem., 2003;278:28181-28192
89. Saad M. F., Greco S., Osei K., Lewin A. J., Edwards C., Nunez M., Reinhardt R. R.: Ragaglitazar Dose-Ranging Study Group. Ragaglitazar improves glycemic control and lipid profile in type 2 diabetic subjects: a 12-week, double-blind, placebo-controlled dose-ranging study with an open pioglitazone arm. Diabetes Care, 2004;27:1324-1329
90. Salvadó L., Serrano-Marco L., Barroso E., Palomer X., Vázquez-Carrera M.: Targeting PPARβ/δ for the treatment of type 2 diabetes mellitus. Expert. Opin. Ther. Targets, 2012;16:209-223
91. Sanghera D. K., Demirci F. Y., Been L., Ortega L., Ralhan S., Wander G. S., Mehra N. K., Singh J., Aston C. E., Mulvihill J. J., Kamboh I. M.: PPARG and ADIPOQ gene polymorphisms increase type 2 diabetes mellitus risk in Asian Indian Sikhs: Pro12Ala still remains as the strongest predictor. Metabolism, 2010;59:492-501
92. Schoonjans K., Peinado-Onsurbe J., Lefebvre A. M., Heyman R. A., Briggs M., Deeb S., Staels B., Auwerx J.: PPARα and PPARγ activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J., 1996;15:5336-5348
93. Shao D., Rangwala S. M., Bailey S. T., Krakow S. L., Reginato M. J., Lazar M. A.: Interdomain communication regulating ligand binding by PPAR-γ. Nature, 1998;396:377-380
94. Shehzad A., Iqbal W., Shehzad O., Lee Y. S.: Adiponectin: regulation of its production and its role in human diseases. Hormones, 2012;11:8-20
95. Shi H., Yu X., Li Q., Ye X., Gao Y., Ma J., Cheng J., Lu Y., Du W., Du J., Ye Q., Zhao X., Zhou L.: Association between PPAR-γ and RXR-α gene polymorphism and metabolic syndrome risk: a case-control study of a Chinese Han population. Arch. Med. Res., 2012;43:233-242
96. Shibata T., Takeuchi S., Yokota S., Kakimoto K., Yonemori F., Wakitani K.: Effects of peroxisome proliferator-activated receptor-α and - γ agonist, JTT-501, on diabetic complications in Zucker diabetic fatty rats. Br. J. Pharmacol., 2000;130:495-504
97. Shulman G. I.: Cellular mechanisms of insulin resistance. J. Clin. Invest., 2000;106:171-176
98. Simón I., Vendrell J., Gutiérrez C., Fernández-Real J. M., Vendrell I., Gallart L., Fontova R., Richart C.: Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma is associated with increased leptin levels in women with type-2 diabetes mellitus. Horm. Res., 2002;58:143-149
99. Singh Ahuja H., Liu S., Crombie D. L., Boehm M., Leibowitz M. D., Heyman R. A., Depre C., Nagy L., Tontonoz P., Davies P. J.: Differential effects of rexinoids and thiazolidinediones on metabolic gene expression in diabetic rodents. Mol. Pharmacol., 2001;59:765-773
100. Smith U., Gogg S., Johansson A., Olausson T., Rotter V., Svalstedt B.: Thiazolidinediones (PPARγ agonists) but not PPARα agonists increase IRS-2 gene expression in 3T3-L1 and human adipocytes. FASEB J., 2001;15:215-220
101. Stephens J. M., Pekala P. H.: Transcriptional repression of the C/EBP-α and GLUT4 genes in 3T3-L1 adipocytes by tumor necrosis factor-α. Regulations is coordinate and independent of protein synthesis. J. Biol. Chem., 1992;267:13580-13584
102. Steppan C. M., Bailey S. T., Bhat S., Brown E. J., Banerjee R. R., Wright C. M., Patel H. R., Ahima R. S., Lazar M. A.: The hormone resistin links obesity to diabetes. Nature, 2001;409:307-312
103. Tack C. J., Smits P.: Thiazolidinedione derivatives in type 2 diabetes mellitus. Neth. J. Med., 2006;64:166-174
104. Tai E. S., Corella D., Deurenberg-Yap M., Adiconis X., Chew S. K., Tan C. E., Ordovas J. M.: Differential effects of the C1431T and Pro12Ala PPARγ gene variants on plasma lipids and diabetes risk in an Asian population. J. Lipid Res., 2004;45:674-685
105. Takata N., Awata T., Inukai K., Watanabe M., Ohkubo T., Kurihara S., Inaba M., Katayama S.: Pro12Ala substitution in peroxisome proliferator- activated receptor γ2 is associated with low adiponectin concentrations in young Japanese men. Metabolism, 2004;53:1548-1551
106. Teboul L., Febbraio M., Gaillard D., Amri E. Z., Silverstein R., Grimaldi P. A.: Structural and functional characterization of the mouse fatty acid translocase promoter: activation during adipose differentiation. Biochem. J., 2001;360:305-312
107. Tomlinson J. W., Walker E. A., Bujalska I. J., Draper N., Lavery G. G., Cooper M. S., Hewison M., Stewart P. M.: 11β-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocr. Rev., 2004;25:831-866
108. Tontonoz P., Hu E., Spiegelman B. M.: Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor. Cell, 1994;79:1147-1156
109. Tontonoz P., Nagy L., Alvarez J. G., Thomazy V. A., Evans R. M.: PPARγ promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell, 1998;93:241-252
110. Tordjman J., Chauvet G., Quette J., Beale E. G., Forest C., Antoine B.: Thiazolidinediones block fatty acid release by inducing glyceroneogenesis in fat cells. J. Biol. Chem., 2003;278:18785-18790
111. Toyoshima Y., Gavrilova O., Yakar S., Jou W., Pack S., Asghar Z., Wheeler M. B., LeRoith D.: Leptin improves insulin resistance and hyperglycemia in a mouse model of type 2 diabetes. Endocrinology, 2005;146:4024-4035
112. Ueki K., Kondo T., Kahn C. R.: Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms. Mol. Cell. Biol., 2004;24:5434-5446
113. Valve R., Sivenius K., Miettinen R., Pihlajamäki J., Rissanen A., Deeb S. S., Auwerx J., Uusitupa M., Laakso M.: Two polymorphisms in the peroxisome proliferator-activated receptor-γ gene are associated with severe overweight among obese women. J. Clin. Endocrinol. Metab., 1999;84:3708-3712
114. van Wijk J. P., de Koning E. J., Martens E. P., Rabelink T. J.: Thiazolidinediones and blood lipids in type 2 diabetes. Arterioscler. Thromb. Vasc. Biol., 2003;23:1744-1749
115. Vidal-Puig A. J., Considine R. V., Jimenez-Liñan M., Werman A., Pories W. J., Caro J. F., Flier J. S.: Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J. Clin. Invest., 1997;99:2416-2422
116. Vigouroux C., Fajas L., Khallouf E., Meier M., Gyapay G., Lascols O., Auwerx J., Weissenbach J., Capeau J., Magre J.: Human peroxisome proliferator-activated receptor-γ2: genetic mapping, identification of a variant in the coding sequence, and exclusion as the gene responsible for lipoatrophic diabetes. Diabetes, 1998;47:490-492
117. Wahli W.: Peroxisome proliferator-activated receptors (PPARs): from metabolic control to epidermal wound healing. Swiss. Med. Wkly., 2002;132:83-91
118. Wake D. J., Stimson R. H., Tan G. D., Homer N. Z., Andrew R., Karpe F., Walker B. R.: Effects of peroxisome proliferator-activated receptor-α and - γ agonists on 11β-hydroxysteroid dehydrogenase type 1 in subcutaneous adipose tissue in men. J. Clin. Endocrinol. Metab., 2007;92:1848-1856
119. Way J. M., Görgün C. Z., Tong Q., Uysal K. T., Brown K. K., Harrington W. W., Oliver W. R. Jr, Willson T. M., Kliewer S. A., Hotamisligil G. S.: Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor γ agonists. J. Biol. Chem., 2001;276:25651-25653
120. Wellen K. E., Hotamisligil G. S.: Inflammation, stress, and diabetes. J. Clin. Invest., 2005;115:1111-1119
121. Wu Z., Xie Y., Morrison R. F., Bucher N. L., Farmer S. R.: PPARγ induces the insulin-dependent glucose transporter GLUT4 in the absence of C/EBPα during the conversion of 3T3 fibroblasts into adipocytes. J. Clin. Invest., 1998;101:22-32
122. Xu H. E., Lambert M. H., Montana V. G., Plunket K. D., Moore L. B., Collins J. L., Oplinger J. A., Kliewer S. A., Gampe R. T. Jr, McKee D. D., Moore J. T., Willson T. M.: Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors. Proc. Natl. Acad. Sci. USA, 2001;98:13919-13924
123. Yang W. S., Lee W. J., Funahashi T., Tanaka S., Matsuzawa Y., Chao C. L., Chen C. L., Tai T. Y., Chuang L. M.: Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J. Clin. Endocrinol. Metab., 2001;86:3815-3819
124. Yao-Borengasser A., Rassouli N., Varma V., Bodles A. M., Rasouli N., Unal R., Phanavanh B., Ranganathan G., McGehee R. E. Jr, Kern P. A.: Stearoyl-coenzyme A desaturase1 gene expression increases after pioglitazone treatment and is associated with peroxisomal proliferator-activated receptor-γ responsiveness. J. Clin. Endocrinol. Metab., 2008;93:4431-4439
125. Yaspelkis B. B., Ansari L., Ramey E. L., Holland G. J., Loy S. F.: Chronic leptin administration increases insulin-stimulated skeletal muscle glucose uptake and transport. Metabolism, 1999;48:671-676
126. Yen C. J., Beamer B. A., Negri C., Silver K., Brown K. A., Yarnall D. P., Burns D. K., Roth J., Shuldiner A. R.: Molecular scanning of the human peroxisome proliferator activated receptor γ (hPPARγ) gene in diabetic Caucasians: identification of a Pro12Ala PPARγ 2 missense mutation. Biochem. Biophys. Res. Commun., 1997;241:270-274
127. Yessoufou A., Wahli W.: Multifaceted roles of peroxisome proliferator-activated receptors (PPARs) at the cellular and whole organism levels. Swiss. Med. Wkly., 2010;140:w13071
128. Zhang F., Lavan B. E., Gregoire F. M.: Selective modulators of PPAR-γ activity: molecular aspects related to obesity and side-effects. PPAR Res., 2007;2007:32696
129. Zhu Y., Qi C., Jain S., Rao M. S., Reddy J. K.: Isolation and characterization of PBP, a protein that interacts with peroxisome proliferator-activated receptor. J. Biol. Chem., 1997;272:25500-25506
130. Zieleniak A., Wójcik M., Woźniak L. A.: Structure and physiological functions of the human peroxisome proliferator-activated receptor gamma. Arch. Immunol. Ther. Exp., 2008;56:331-345