Roles of oxidative stress, adiponectin, and nuclear hormone receptors in obesity-associated insulin resistance and cardiovascular risk

Hormone Molecular Biology and Clinical Investigation

Volumn 19, Issue 2, 2014, Pages 75-88

  Matsuda, Morihiro ^a   Shimomura, Iichiro ^b  

^a NATIONAL HOSPITAL ORGANIZATION   (Japan)

^b OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

adipocytes; adiponectin; nuclear hormone receptors; obesity; oxidative stress

Indexed keywords

ADIPONECTIN; ALDOSTERONE; GLUCOCORTICOID; HORMONE RECEPTOR; INSULIN; LIGAND; LIVER X RECEPTOR; MINERALOCORTICOID RECEPTOR; NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; NUCLEAR HORMONE RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; REACTIVE OXYGEN METABOLITE; UNCLASSIFIED DRUG; CELL RECEPTOR;

ADIPOSE TISSUE; ANTIINFLAMMATORY ACTIVITY; ATHEROGENESIS; ATHEROSCLEROSIS; CARDIOVASCULAR RISK; CHRONIC INFLAMMATION; DIABETES MELLITUS; ENZYME ACTIVITY; GENETIC TRANSCRIPTION; HUMAN; HYPERTENSION; INSULIN RESISTANCE; LIGAND BINDING; MACROPHAGE; MITOCHONDRION; NONHUMAN; OBESITY; OVERNUTRITION; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; CARDIOVASCULAR DISEASES; COMPLICATION; METABOLISM; RISK FACTOR;

ADIPONECTIN; CARDIOVASCULAR DISEASES; HUMANS; INSULIN RESISTANCE; OBESITY; OXIDATIVE STRESS; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RISK FACTORS;

EID: 84928648992     PISSN: 18681883     EISSN: 18681891     Source Type: Journal    
DOI: 10.1515/hmbci-2014-0001     Document Type: Review

References (145)

1. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000;894:i-xii, 1-253.
2. Matsuzawa Y, Nakamura T, Shimomura I, Kotani K. Visceral fat accumulation and cardiovascular disease. Obes Res 1995;3:645S-7S.
3. Matsuzawa Y, Shimomura I, Nakamura T, Keno Y, Kotani K, Tokunaga K. Pathophysiology and pathogenesis of visceral fat obesity. Obes Res 1995;3:187S-94S.
4. Vucenik I, Stains JP. Obesity and cancer risk: evidence, mechanisms, and recommendations. Ann NY Acad Sci 2012;1271:37-43.
5. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen MR, Groop L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001;24:683-9.
6. Matsuzawa Y, Funahashi T, Nakamura T. The concept of metabolic syndrome: contribution of visceral fat accumulation and its molecular mechanism. J Atheroscler Thromb 2011;18:629-39.
7. Matsuzawa Y, Funahashi T, Nakamura T. Molecular mechanism of metabolic syndrome X: contribution of adipocytokines adipocyte-derived bioactive substances. Ann NY Acad Sci 1999;892:146-54.
8. Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem Biophys Res Commun 1996;221:286-9.
9. Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 2002;8:731-7.
10. Matsuda M, Shimomura I, Sata M, Arita Y, Nishida M, Maeda N, Kumada M, Okamoto Y, Nagaretani H, Nishizawa H, Kishida K, Komuro R, Ouchi N, Kihara S, Nagai R, Funahashi T, Matsuzawa Y. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Biol Chem 2002;277:37487-91.
11. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999;257:79-83.
12. Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000;20:1595-9.
13. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003;112:1796-808.
14. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003;112:1821-30.
15. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993;259:87-91.
16. Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab 1998;83:847-50.
17. Sartipy P, Loskutoff DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci USA 2003;100:7265-70.
18. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004;114:1752-61.
19. Matsuoka T, Kajimoto Y, Watada H, Kaneto H, Kishimoto M, Umayahara Y, Fujitani Y, Kamada T, Kawamori R, Yamasaki Y. Glycation-dependent, reactive oxygen species-mediated suppression of the insulin gene promoter activity in HIT cells. J Clin Invest 1997;99:144-50.
20. Kaneto H, Kajimoto Y, Miyagawa J, Matsuoka T, Fujitani Y, Umayahara Y, Hanafusa T, Matsuzawa Y, Yamasaki Y, Hori M. Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity. Diabetes 1999;48:2398-406.
21. Rajagopalan S, Kurz S, Munzel T, Tarpey M, Freeman BA, Griendling KK, Harrison DG. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 1996;97:1916-23.
22. Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 2001;104:2673-8.
23. Zhang X, Dong F, Ren J, Driscoll MJ, Culver B. High dietary fat induces NADPH oxidase-associated oxidative stress and inflammation in rat cerebral cortex. Exp Neurol 2005;191: 318-25.
24. Nagae A, Fujita M, Kawarazaki H, Matsui H, Ando K, Fujita T. Sympathoexcitation by oxidative stress in the brain mediates arterial pressure elevation in obesity-induced hypertension. Circulation 2009;119:978-86.
25. Bookout AL, Jeong Y, Downes M, Yu RT, Evans RM, Mangelsdorf DJ. Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell 2006;126:789-99.
26. Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 1990;347:645-50.
27. Iwaki M, Matsuda M, Maeda N, Funahashi T, Matsuzawa Y, Makishima M, Shimomura I. Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes 2003;52:1655-63.
28. Okuno Y, Matsuda M, Kobayashi H, Morita K, Suzuki E, Fukuhara A, Komuro R, Shimabukuro M, Shimomura I. Adipose expression of catalase is regulated via a novel remote PPARgamma-responsive region. Biochem Biophys Res Commun 2008;366:698-704.
29. Okuno Y, Matsuda M, Miyata Y, Fukuhara A, Komuro R, Shimabukuro M, Shimomura I. Human catalase gene is regulated by peroxisome proliferator activated receptor-gamma through a response element distinct from that of mouse. Endocr J 2010;57:303-9.
30. Heo KS, Kim DU, Ryoo S, Nam M, Baek ST, Kim L, Park SK, Myung CS, Hoe KL. PPARgamma activation abolishes LDL-induced proliferation of human aortic smooth muscle cells via SOD-mediated down-regulation of superoxide. Biochem Biophys Res Commun 2007;359:1017-23.
31. Lee YS, Kim AY, Choi JW, Kim M, Yasue S, Son HJ, Masuzaki H, Park KS, Kim JB. Dysregulation of adipose glutathione peroxidase 3 in obesity contributes to local and systemic oxidative stress. Mol Endocrinol 2008;22:2176-89.
32. Guo C, Ricchiuti V, Lian BQ, Yao TM, Coutinho P, Romero JR, Li J, Williams GH, Adler GK. Mineralocorticoid receptor blockade reverses obesity-related changes in expression of adiponectin, peroxisome proliferator-activated receptor-gamma, and proinflammatory adipokines. Circulation 2008;117:2253-61.
33. Hirata A, Maeda N, Hiuge A, Hibuse T, Fujita K, Okada T, Kihara S, Funahashi T, Shimomura I. Blockade of mineralocorticoid receptor reverses adipocyte dysfunction and insulin resistance in obese mice. Cardiovasc Res 2009;84:164-72.
34. Hirata A, Maeda N, Nakatsuji H, Hiuge-Shimizu A, Okada T, Funahashi T, Shimomura I. Contribution of glucocorticoid-mineralocorticoid receptor pathway on the obesity-related adipocyte dysfunction. Biochem Biophys Res Commun 2012;419:182-7.
35. Keaney JF Jr., Larson MG, Vasan RS, Wilson PW, Lipinska I, Corey D, Massaro JM, Sutherland P, Vita JA, Benjamin EJ. Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler Thromb Vasc Biol 2003;23:434-9.
36. Fujita K, Nishizawa H, Funahashi T, Shimomura I, Shimabukuro M. Systemic oxidative stress is associated with visceral fat accumulation and the metabolic syndrome. Circ J 2006;70:1437-42.
37. Kobayashi H, Matsuda M, Fukuhara A, Komuro R, Shimomura I. Dysregulated glutathione metabolism links to impaired insulin action in adipocytes. Am J Physiol Endocrinol Metab 2009;296:E1326-34.
38. Curzio M, Esterbauer H, Poli G, Biasi F, Cecchini G, Di Mauro C, Cappello N, Dianzani MU. Possible role of aldehydic lipid peroxidation products as chemoattractants. Int J Tissue React 1987;9:295-306.
39. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005;54:1615-25.
40. Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, Sano H, Utsumi H, Nawata H. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 2000;49:1939-45.
41. Houstis N, Rosen ED, Lander ES. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 2006;440:944-8.
42. Rudich A, Tirosh A, Potashnik R, Hemi R, Kanety H, Bashan N. Prolonged oxidative stress impairs insulin-induced GLUT4 translocation in 3T3-L1 adipocytes. Diabetes 1998;47:1562-9.
43. Tirosh A, Potashnik R, Bashan N, Rudich A. Oxidative stress disrupts insulin-induced cellular redistribution of insulin receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3-L1 adipocytes. A putative cellular mechanism for impaired protein kinase B activation and GLUT4 translocation. J Biol Chem 1999;274:10595-602.
44. Krieger-Brauer HI, Kather H. Human fat cells possess a plasma membrane-bound H2O2-generating system that is activated by insulin via a mechanism bypassing the receptor kinase. J Clin Invest 1992;89:1006-13.
45. Maddux BA, See W, Lawrence JC Jr., Goldfine AL, Goldfine ID, Evans JL. Protection against oxidative stress-induced insulin resistance in rat L6 muscle cells by mircomolar concentrations of alpha-lipoic acid. Diabetes 2001;50:404-10.
46. Matsuoka TA, Zhao L, Artner I, Jarrett HW, Friedman D, Means A, Stein R. Members of the large Maf transcription family regulate insulin gene transcription in islet beta cells. Mol Cell Biol 2003;23:6049-62.
47. Stocker R, Keaney JF Jr. Role of oxidative modifications in atherosclerosis. Physiol Rev 2004;84:1381-478.
48. Azumi H, Inoue N, Ohashi Y, Terashima M, Mori T, Fujita H, Awano K, Kobayashi K, Maeda K, Hata K, Shinke T, Kobayashi S, Hirata K, Kawashima S, Itabe H, Hayashi Y, Imajoh-Ohmi S, Itoh H, Yokoyama M. Superoxide generation in directional coronary atherectomy specimens of patients with angina pectoris: important role of NAD(P)H oxidase. Arterioscler Thromb Vasc Biol 2002;22:1838-44.
49. Guzik TJ, Sadowski J, Kapelak B, Jopek A, Rudzinski P, Pillai R, Korbut R, Channon KM. Systemic regulation of vascular NAD(P) H oxidase activity and nox isoform expression in human arteries and veins. Arterioscler Thromb Vasc Biol 2004;24:1614-20.
50. Spiekermann S, Landmesser U, Dikalov S, Bredt M, Gamez G, Tatge H, Reepschlager N, Hornig B, Drexler H, Harrison DG. Electron spin resonance characterization of vascular xanthine and NAD(P)H oxidase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. Circulation 2003;107:1383-9.
51. Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 2000;86: 494-501.
52. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001;414:813-20.
53. Jay D, Hitomi H, Griendling KK. Oxidative stress and diabetic cardiovascular complications. Free Radic Biol Med 2006;40:183-92.
54. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000;404:787-90.
55. Sasaki S, Inoguchi T. The role of oxidative stress in the pathogenesis of diabetic vascular complications. Diabetes Metab J 2012;36:255-61.
56. Basta G, Schmidt AM, De Caterina R. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovasc Res 2004;63:582-92.
57. Ceriello A, Taboga C, Tonutti L, Quagliaro L, Piconi L, Bais B, Da Ros R, Motz E. Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short-and long-term simvastatin treatment. Circulation 2002;106:1211-8.
58. Anderson RA, Evans ML, Ellis GR, Graham J, Morris K, Jackson SK, Lewis MJ, Rees A, Frenneaux MP. The relationships between post-prandial lipaemia, endothelial function and oxidative stress in healthy individuals and patients with type 2 diabetes. Atherosclerosis 2001;154:475-83.
59. Matsuda M, Tamura R, Kanno K, Segawa T, Kinoshita H, Nishimoto O, Nishiyama H, Kawamoto T. Impact of dyslipidemic components of metabolic syndrome, adiponectin levels, and anti-diabetes medications on malondialdehyde-modified low-density lipoprotein levels in statin-treated diabetes patients with coronary artery disease. Diabetol Metab Syndr 2013;5:77.
60. Shin HK, Kim YK, Kim KY, Lee JH, Hong KW. Remnant lipoprotein particles induce apoptosis in endothelial cells by NAD(P)H oxidase-mediated production of superoxide and cytokines via lectin-like oxidized low-density lipoprotein receptor-1 activation: prevention by cilostazol. Circulation 2004;109:1022-8.
61. Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman AM, Navab M. Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 1995;96:2882-91.
62. Stefan N, Vozarova B, Funahashi T, Matsuzawa Y, Weyer C, Lindsay RS, Youngren JF, Havel PJ, Pratley RE, Bogardus C, Tataranni PA. Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. Diabetes 2002;51:1884-8.
63. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001;86:1930-5.
64. Lindsay RS, Funahashi T, Hanson RL, Matsuzawa Y, Tanaka S, Tataranni PA, Knowler WC, Krakoff J. Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 2002;360:57-8.
65. Iwashima Y, Katsuya T, Ishikawa K, Ouchi N, Ohishi M, Sugimoto K, Fu Y, Motone M, Yamamoto K, Matsuo A, Ohashi K, Kihara S, Funahashi T, Rakugi H, Matsuzawa Y, Ogihara T. Hypoadi-ponectinemia is an independent risk factor for hypertension. Hypertension 2004;43:1318-23.
66. Ryo M, Nakamura T, Kihara S, Kumada M, Shibazaki S, Takahashi M, Nagai M, Matsuzawa Y, Funahashi T. Adiponectin as a biomarker of the metabolic syndrome. Circ J 2004;68:975-81.
67. Kondo H, Shimomura I, Matsukawa Y, Kumada M, Takahashi M, Matsuda M, Ouchi N, Kihara S, Kawamoto T, Sumitsuji S, Funahashi T, Matsuzawa Y. Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. Diabetes 2002;51:2325-8.
68. Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N, Arita Y, Okamoto Y, Shimomura I, Hiraoka H, Nakamura T, Funahashi T, Matsuzawa Y. Association of hypoadi-ponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 2003;23:85-9.
69. Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. J Am Med Assoc 2004;291:1730-7.
70. Marso SP, Mehta SK, Frutkin A, House JA, McCrary JR, Kulkarni KR. Low adiponectin levels are associated with atherogenic dyslipidemia and lipid-rich plaque in nondiabetic coronary arteries. Diabetes Care 2008;31:989-94.
71. Matsuda M, Tamura R, Kishida N, Segawa T, Kanno K, Nishimoto O, Nakamoto K, Nishiyama H, Kawamoto T. Predictive value of adiponectin in patients with multivessel coronary athero sclerosis detected on computed tomography angiography. J Atheroscler Thromb 2013;20:767-76.
72. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001;7:941-6.
73. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003;423:762-9.
74. Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M, Okada-Iwabu M, Kawamoto S, Kubota N, Kubota T, Ito Y, Kamon J, Tsuchida A, Kumagai K, Kozono H, Hada Y, Ogata H, Tokuyama K, Tsunoda M, Ide T, Murakami K, Awazawa M, Takamoto I, Froguel P, Hara K, Tobe K, Nagai R, Ueki K, Kadowaki T. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med 2007;13:332-9.
75. Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, Ohashi K, Sakai N, Shimomura I, Kobayashi H, Terasaka N, Inaba T, Funahashi T, Matsuzawa Y. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 2002;106:2767-70.
76. Yamauchi T, Kamon J, Waki H, Imai Y, Shimozawa N, Hioki K, Uchida S, Ito Y, Takakuwa K, Matsui J, Takata M, Eto K, Terauchi Y, Komeda K, Tsunoda M, Murakami K, Ohnishi Y, Naitoh T, Yamamura K, Ueyama Y, Froguel P, Kimura S, Nagai R, Kadowaki T. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem 2003;278:2461-8.
77. Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, Nishida M, Takahashi M, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation 2000;102:1296-301.
78. Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 2000;96:1723-32.
79. Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y, Ishigami M, Kuriyama H, Kishida K, Nishizawa H, Hotta K, Muraguchi M, Ohmoto Y, Yamashita S, Funahashi T, Matsuzawa Y. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 2001;103:1057-63.
80. Arita Y, Kihara S, Ouchi N, Maeda K, Kuriyama H, Okamoto Y, Kumada M, Hotta K, Nishida M, Takahashi M, Nakamura T, Shimomura I, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell. Circulation 2002;105:2893-8.
81. Kumada M, Kihara S, Ouchi N, Kobayashi H, Okamoto Y, Ohashi K, Maeda K, Nagaretani H, Kishida K, Maeda N, Nagasawa A, Funahashi T, Matsuzawa Y. Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation 2004;109:2046-9.
82. Komura N, Maeda N, Mori T, Kihara S, Nakatsuji H, Hirata A, Tochino Y, Funahashi T, Shimomura I. Adiponectin protein exists in aortic endothelial cells. PLoS One 2013;8:e71271.
83. Matsuura F, Oku H, Koseki M, Sandoval JC, Yuasa-Kawase M, Tsubakio-Yamamoto K, Masuda D, Maeda N, Tsujii K, Ishigami M, Nishida M, Hirano K, Kihara S, Hori M, Shimomura I, Yamashita S. Adiponectin accelerates reverse cholesterol transport by increasing high density lipoprotein assembly in the liver. Biochem Biophys Res Commun 2007;358:1091-5.
84. Oku H, Matsuura F, Koseki M, Sandoval JC, Yuasa-Kawase M, Tsubakio-Yamamoto K, Masuda D, Maeda N, Ohama T, Ishigami M, Nishida M, Hirano K, Kihara S, Hori M, Shimomura I, Yamashita S. Adiponectin deficiency suppresses ABCA1 expression and ApoA-I synthesis in the liver. FEBS Lett 2007;581:5029-33.
85. Shibata R, Ouchi N, Ito M, Kihara S, Shiojima I, Pimentel DR, Kumada M, Sato K, Schiekofer S, Ohashi K, Funahashi T, Colucci WS, Walsh K. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med 2004;10:1384-9.
86. Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, Funahashi T, Ouchi N, Walsh K. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK-and COX-2-dependent mechanisms. Nat Med 2005;11:1096-103.
87. Fujita K, Maeda N, Sonoda M, Ohashi K, Hibuse T, Nishizawa H, Nishida M, Hiuge A, Kurata A, Kihara S, Shimomura I, Funahashi T. Adiponectin protects against angiotensin II-induced cardiac fibrosis through activation of PPAR-alpha. Arterioscler Thromb Vasc Biol 2008;28:863-70.
88. Tao L, Gao E, Jiao X, Yuan Y, Li S, Christopher TA, Lopez BL, Koch W, Chan L, Goldstein BJ, Ma XL. Adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress. Circulation 2007;115:1408-16.
89. Wang Y, Gao E, Tao L, Lau WB, Yuan Y, Goldstein BJ, Lopez BL, Christopher TA, Tian R, Koch W, Ma XL. AMP-activated protein kinase deficiency enhances myocardial ischemia/reperfusion injury but has minimal effect on the antioxidant/antinitrative protection of adiponectin. Circulation 2009;119:835-44.
90. Li R, Wang WQ, Zhang H, Yang X, Fan Q, Christopher TA, Lopez BL, Tao L, Goldstein BJ, Gao F, Ma XL. Adiponectin improves endothelial function in hyperlipidemic rats by reducing oxidative/nitrative stress and differential regulation of eNOS/iNOS activity. Am J Physiol Endocrinol Metab 2007;293:E1703-8.
91. Essick EE, Ouchi N, Wilson RM, Ohashi K, Ghobrial J, Shibata R, Pimentel DR, Sam F. Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte remodeling. Am J Physiol Heart Circ Physiol 2011;301:H984-93.
92. Yi W, Sun Y, Gao E, Wei X, Lau WB, Zheng Q, Wang Y, Yuan Y, Wang X, Tao L, Li R, Koch W, Ma XL. Reduced cardioprotective action of adiponectin in high-fat diet-induced type II diabetic mice and its underlying mechanisms. Antioxid Redox Signal 2011;15:1779-88.
93. Tsuchida A, Yamauchi T, Ito Y, Hada Y, Maki T, Takekawa S, Kamon J, Kobayashi M, Suzuki R, Hara K, Kubota N, Terauchi Y, Froguel P, Nakae J, Kasuga M, Accili D, Tobe K, Ueki K, Nagai R, Kadowaki T. Insulin/Foxo1 pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity. J Biol Chem 2004;279:30817-22.
94. 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. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 2001;50:2094-9.
95. 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;281:8748-55.
96. Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, Skene AM, Tan MH, Lefebvre PJ, Murray GD, Standl E, Wilcox RG, Wilhelmsen L, Betteridge J, Birkeland K, Golay A, Heine RJ, Koranyi L, Laakso M, Mokan M, Norkus A, Pirags V, Podar T, Scheen A, Scherbaum W, Schernthaner G, Schmitz O, Skrha J, Smith U, Taton J. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005;366:1279-89.
97. Duval C, Muller M, Kersten S. PPARalpha and dyslipidemia. Biochim Biophys Acta 2007;1771:961-71.
98. Hiuge A, Tenenbaum A, Maeda N, Benderly M, Kumada M, Fisman EZ, Tanne D, Matas Z, Hibuse T, Fujita K, Nishizawa H, Adler Y, Motro M, Kihara S, Shimomura I, Behar S, Funahashi T. Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level. Arterioscler Thromb Vasc Biol 2007;27:635-41.
99. The Bezafibrate Infarction Prevention (BIP) Study Group. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. Circulation 2000;102:21-7.
100. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, Forder P, Pillai A, Davis T, Glasziou P, Drury P, Kesaniemi YA, Sullivan D, Hunt D, Colman P, d'Emden M, Whiting M, Ehnholm C, Laakso M. Efects of long-term fenofbrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005;366:1849-61.
101. Dressel U, Allen TL, Pippal JB, Rohde PR, Lau P, Muscat GE. The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells. Mol Endocrinol 2003;17:2477-93.
102. Luquet S, Lopez-Soriano J, Holst D, Fredenrich A, Melki J, Ras-soulzadegan M, Grimaldi PA. Peroxisome proliferator-activated receptor delta controls muscle development and oxidative capability. FASEB J 2003;17:2299-301.
103. Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Kang H, Evans RM. Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. Cell 2003;113:159-70.
104. Viengchareun S, Le Menuet D, Martinerie L, Munier M, Pascual-Le Tallec L, Lombes M. The mineralocorticoid receptor: insights into its molecular and (patho)physiological biology. Nucl Recept Signal 2007;5:e012.
105. Callera GE, Touyz RM, Tostes RC, Yogi A, He Y, Malkinson S, Schifrin EL. Aldosterone activates vascular p38MAP kinase and NADPH oxidase via c-Src. Hypertension 2005;45:773-9.
106. Funder JW. Mineralocorticoid receptors: distribution and activation. Heart Fail Rev 2005;10:15-22.
107. Caprio M, Feve B, Claes A, Viengchareun S, Lombes M, Zennaro MC. Pivotal role of the mineralocorticoid receptor in corticos-teroid-induced adipogenesis. FASEB J 2007;21:2185-94.
108. Caprio M, Antelmi A, Chetrite G, Muscat A, Mammi C, Marzolla V, Fabbri A, Zennaro MC, Feve B. Antiadipogenic efects of the mineralocorticoid receptor antagonist drospirenone: potential implications for the treatment of metabolic syndrome. Endocrinology 2011;152:113-25.
109. Bujalska IJ, Kumar S, Stewart PM. Does central obesity reflect "Cushing's disease of the omentum"? Lancet 1997;349:1210-3.
110. Engeli S, Bohnke J, Feldpausch M, Gorzelniak K, Heintze U, Janke J, Luf FC, Sharma AM. Regulation of 11beta-HSD genes in human adipose tissue: influence of central obesity and weight loss. Obes Res 2004;12:9-17.
111. Wake DJ, Rask E, Livingstone DE, Soderberg S, Olsson T, Walker BR. Local and systemic impact of transcriptional up-regulation of 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue in human obesity. J Clin Endocrinol Metab 2003;88:3983-8.
112. Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, Flier JS. A transgenic model of visceral obesity and the metabolic syndrome. Science 2001;294:2166-70.
113. Berger J, Tanen M, Elbrecht A, Hermanowski-Vosatka A, Moller DE, Wright SD, Thieringer R. Peroxisome proliferator-activated receptor-gamma ligands inhibit adipocyte 11beta-hydroxyster-oid dehydrogenase type 1 expression and activity. J Biol Chem 2001;276:12629-35.
114. Zennaro MC, Caprio M, Feve B. Mineralocorticoid receptors in the metabolic syndrome. Trends Endocrinol Metab 2009;20:444-51.
115. Hoppmann J, Perwitz N, Meier B, Fasshauer M, Hadaschik D, Lehnert H, Klein J. The balance between gluco-and mineralo-corticoid action critically determines inflammatory adipocyte responses. J Endocrinol 2010;204:153-64.
116. Oakley RH, Ren R, Cruz-Topete D, Bird GS, Myers PH, Boyle MC, Schneider MD, Willis MS, Cidlowski JA. Essential role of stress hormone signaling in cardiomyocytes for the prevention of heart disease. Proc Natl Acad Sci USA 2013;110:17035-40.
117. Repa JJ, Mangelsdorf DJ. The role of orphan nuclear receptors in the regulation of cholesterol homeostasis. Annu Rev Cell Dev Biol 2000;16:459-81.
118. Venkateswaran A, Laftte BA, Joseph SB, Mak PA, Wilpitz DC, Edwards PA, Tontonoz P. Control of cellular cholesterol eflux by the nuclear oxysterol receptor LXR alpha. Proc Natl Acad Sci USA 2000;97:12097-102.
119. Repa JJ, Turley SD, Lobaccaro JA, Medina J, Li L, Lustig K, Shan B, Heyman RA, Dietschy JM, Mangelsdorf DJ. Regulation of absorption and ABC1-mediated eflux of cholesterol by RXR heterodimers. Science 2000;289:1524-9.
120. Joseph SB, McKilligin E, Pei L, Watson MA, Collins AR, Laftte BA, Chen M, Noh G, Goodman J, Hagger GN, Tran J, Tippin TK, Wang X, Lusis AJ, Hsueh WA, Law RE, Collins JL, Willson TM, Tontonoz P. Synthetic LXR ligand inhibits the development of atherosclerosis in mice. Proc Natl Acad Sci USA 2002;99:7604-9.
121. Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, Shan B, Brown MS, Goldstein JL, Mangelsdorf DJ. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev 2000;14:2819-30.
122. Inaba T, Matsuda M, Shimamura M, Takei N, Terasaka N, Ando Y, Yasumo H, Koishi R, Makishima M, Shimomura I. Angiopoie-tin-like protein 3 mediates hypertriglyceridemia induced by the liver X receptor. J Biol Chem 2003;278:21344-51.
123. Hummasti S, Laftte BA, Watson MA, Galardi C, Chao LC, Rama-murthy L, Moore JT, Tontonoz P. Liver X receptors are regulators of adipocyte gene expression but not diferentiation: identif-cation of apoD as a direct target. J Lipid Res 2004;45:616-25.
124. Gerin I, Dolinsky VW, Shackman JG, Kennedy RT, Chiang SH, Burant CF, Stefensen KR, Gustafsson JA, MacDougald OA. LXR-beta is required for adipocyte growth, glucose homeostasis, and beta cell function. J Biol Chem 2005;280:23024-31.
125. Dalen KT, Ulven SM, Bamberg K, Gustafsson JA, Nebb HI. Expression of the insulin-responsive glucose transporter GLUT4 in adipocytes is dependent on liver X receptor alpha. J Biol Chem 2003;278:48283-91.
126. Laftte BA, Chao LC, Li J, Walczak R, Hummasti S, Joseph SB, Castrillo A, Wilpitz DC, Mangelsdorf DJ, Collins JL, Saez E, Tontonoz P. Activation of liver X receptor improves glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue. Proc Natl Acad Sci USA 2003;100:5419-24.
127. Stenson BM, Ryden M, Stefensen KR, Wahlen K, Pettersson AT, Jocken JW, Arner P, Laurencikiene J. Activation of liver X receptor regulates substrate oxidation in white adipocytes. Endocrinology 2009;150:4104-13.
128. Kalaany NY, Gauthier KC, Zavacki AM, Mammen PP, Kitazume T, Peterson JA, Horton JD, Garry DJ, Bianco AC, Mangelsdorf DJ. LXRs regulate the balance between fat storage and oxidation. Cell Metab 2005;1:231-44.
129. Korach-Andre M, Archer A, Barros RP, Parini P, Gustafsson JA. Both liver-X receptor (LXR) isoforms control energy expenditure by regulating brown adipose tissue activity. Proc Natl Acad Sci USA 2011;108:403-8.
130. Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, Hull MV, Lustig KD, Mangelsdorf DJ, Shan B. Identifcation of a nuclear receptor for bile acids. Science 1999;284:1362-5.
131. Goodwin B, Jones SA, Price RR, Watson MA, McKee DD, Moore LB, Galardi C, Wilson JG, Lewis MC, Roth ME, Maloney PR, Willson TM, Kliewer SA. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell 2000;6:517-26.
132. Lu TT, Makishima M, Repa JJ, Schoonjans K, Kerr TA, Auwerx J, Mangelsdorf DJ. Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol Cell 2000;6:507-15.
133. Prawitt J, Abdelkarim M, Stroeve JH, Popescu I, Duez H, Velagapudi VR, Dumont J, Bouchaert E, van Dijk TH, Lucas A, Dorchies E, Daoudi M, Lestavel S, Gonzalez FJ, Oresic M, Cariou B, Kuipers F, Caron S, Staels B. Farnesoid X receptor defciency improves glucose homeostasis in mouse models of obesity. Diabetes 2011;60:1861-71.
134. Hartman HB, Gardell SJ, Petucci CJ, Wang S, Krueger JA, Evans MJ. Activation of farnesoid X receptor prevents atherosclerotic lesion formation in LDLR-/-and apoE-/-mice. J Lipid Res 2009;50:1090-100.
135. Lee JM, Lee YK, Mamrosh JL, Busby SA, Grifn PR, Pathak MC, Ortlund EA, Moore DD. A nuclear-receptor-dependent phos-phatidylcholine pathway with antidiabetic efects. Nature 2011;474:506-10.
136. Nishigori H, Tomura H, Tonooka N, Kanamori M, Yamada S, Sho K, Inoue I, Kikuchi N, Onigata K, Kojima I, Kohama T, Yamagata K, Yang Q, Matsuzawa Y, Miki T, Seino S, Kim MY, Choi HS, Lee YK, Moore DD, Takeda J. Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects. Proc Natl Acad Sci USA 2001;98:575-80.
137. Park YJ, Kim SC, Kim J, Anakk S, Lee JM, Tseng HT, Yechoor V, Park J, Choi JS, Jang HC, Lee KU, Novak CM, Moore DD, Lee YK. Dissociation of diabetes and obesity in mice lacking orphan nuclear receptor small heterodimer partner. J Lipid Res 2011;52:2234-44.
138. Wang L, Liu J, Saha P, Huang J, Chan L, Spiegelman B, Moore DD. The orphan nuclear receptor SHP regulates PGC-1alpha expression and energy production in brown adipocytes. Cell Metab 2005;2:227-38.
139. Nishizawa H, Yamagata K, Shimomura I, Takahashi M, Kuriyama H, Kishida K, Hotta K, Nagaretani H, Maeda N, Matsuda M, Kihara S, Nakamura T, Nishigori H, Tomura H, Moore DD, Takeda J, Funahashi T, Matsuzawa Y. Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation. J Biol Chem 2002;277:1586-92.
140. Li L, Xie X, Qin J, Jeha GS, Saha PK, Yan J, Haueter CM, Chan L, Tsai SY, Tsai MJ. The nuclear orphan receptor COUP-TFII plays an essential role in adipogenesis, glucose homeostasis, and energy metabolism. Cell Metab 2009;9:77-87.
141. Xu Z, Yu S, Hsu CH, Eguchi J, Rosen ED. The orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II is a critical regulator of adipogenesis. Proc Natl Acad Sci USA 2008;105:2421-6.
142. Duez H, Duhem C, Laitinen S, Patole PS, Abdelkarim M, Bois-Joyeux B, Danan JL, Staels B. Inhibition of adipocyte diferen-tiation by RORalpha. FEBS Lett 2009;583:2031-6.
143. Luo J, Sladek R, Carrier J, Bader JA, Richard D, Giguere V. Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor alpha. Mol Cell Biol 2003;23:7947-56.
144. Kubo M, Ijichi N, Ikeda K, Horie-Inoue K, Takeda S, Inoue S. Modulation of adipogenesis-related gene expression by estrogen-related receptor gamma during adipocytic diferen-tiation. Biochim Biophys Acta 2009;1789:71-7.
145. Kumar N, Solt LA, Wang Y, Rogers PM, Bhattacharyya G, Kamenecka TM, Stayrook KR, Crumbley C, Floyd ZE, Gimble JM, Grifn PR, Burris TP. Regulation of adipogenesis by natural and synthetic REV-ERB ligands. Endocrinology 2010;151:3015-25.