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Roles of adiponectin and oxidative stress in obesity-associated metabolic and cardiovascular diseases

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Abstract

The recent increase in populations with obesity is a worldwide social problem, and the enhanced susceptibility of obese people to metabolic and cardiovascular diseases has become a growing health threat. An understanding of the molecular basis for obesity-associated disease development is required to prevent these diseases. Many studies have revealed that the mechanism involves various bioactive molecules that are released from adipose tissues and designated as adipocytokines/adipokines. Adiponectin is an adipocytokine that exerts insulin-sensitizing effects in the liver and skeletal muscle via adenosine monophosphate-activated protein kinase and proliferator-activated receptor α activation. Additionally, adiponectin can suppress atherosclerosis development in vascular walls via various anti-inflammatory effects. In contrast, oxidative stress is a harmful factor that systemically increases during obesity and promotes the development of diabetes, atherosclerosis, and various other diseases. In obese mice, oxidative stress is enhanced in adipose tissue before diabetes development, but not in the liver, skeletal muscle, and aorta, suggesting that in obesity, adipose tissue may be a major source of reactive oxygen species (ROS). ROS suppress adiponectin production in adipocytes. Treatment of obese mice with anti-oxidative agents improves insulin resistance and restores adiponectin production. Recent studies have demonstrated that adiponectin protects against oxidative stress-induced damage in the vascular endothelium and myocardium. Thus, decreased circulating adiponectin levels and increased oxidative stress, which are closely linked to each other, should be deeply involved in obesity-associated metabolic and cardiovascular disease pathogenesis.

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References

  1. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259(5091):87–91.

    CAS  PubMed  Google Scholar 

  2. 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(3):847–50.

    CAS  PubMed  Google Scholar 

  3. Sartipy P, Loskutoff DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci U S A. 2003;100(12):7265–70.

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395(6704):763–70.

    CAS  PubMed  Google Scholar 

  5. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7(8):941–6.

    CAS  PubMed  Google Scholar 

  6. Berg AH, Combs TP, Du X, Brownlee M, Scherer PE. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med. 2001;7(8):947–53.

    CAS  PubMed  Google Scholar 

  7. Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002;8(7):731–7.

    CAS  PubMed  Google Scholar 

  8. Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002;106(22):2767–70.

    CAS  PubMed  Google Scholar 

  9. Matsuda M, Shimomura I, Sata M, Arita Y, Nishida M, Maeda N, et al. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Biol Chem. 2002;277(40):37487–91.

    CAS  PubMed  Google Scholar 

  10. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257(1):79–83.

    CAS  PubMed  Google Scholar 

  11. Matsuzawa Y, Funahashi T, Nakamura T. Molecular mechanism of metabolic syndrome X: contribution of adipocytokines adipocyte-derived bioactive substances. Ann N Y Acad Sci. 1999;892:146–54.

    CAS  PubMed  Google Scholar 

  12. Spiegelman BM, Flier JS. Obesity and the regulation of energy balance. Cell. 2001;104(4):531–43.

    CAS  PubMed  Google Scholar 

  13. Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest. 2000;106(4):473–81.

    CAS  PubMed Central  PubMed  Google Scholar 

  14. 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(2):286–9.

    CAS  PubMed  Google Scholar 

  15. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation. 1999;100(25):2473–6.

    CAS  PubMed  Google Scholar 

  16. Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 2000;20(6):1595–9.

    CAS  PubMed  Google Scholar 

  17. Matsuoka T, Kajimoto Y, Watada H, Kaneto H, Kishimoto M, Umayahara Y, et al. Glycation-dependent, reactive oxygen species-mediated suppression of the insulin gene promoter activity in HIT cells. J Clin Invest. 1997;99(1):144–50.

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Matsuoka TA, Zhao L, Artner I, Jarrett HW, Friedman D, Means A, et al. Members of the large Maf transcription family regulate insulin gene transcription in islet beta cells. Mol Cell Biol. 2003;23(17):6049–62.

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Stocker R, Keaney Jr JF. Role of oxidative modifications in atherosclerosis. Physiol Rev. 2004;84(4):1381–478.

    CAS  PubMed  Google Scholar 

  20. Fiaschi T, Chiarugi P. Oxidative stress, tumor microenvironment, and metabolic reprogramming: a diabolic liaison. Int J Cell Biol, 2012(Article ID 762825). doi: 10.1155/2012/762825.

  21. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    CAS  PubMed  Google Scholar 

  22. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004;114(12):1752–61.

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Stefan N, Vozarova B, Funahashi T, Matsuzawa Y, Weyer C, Lindsay RS, et al. 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(6):1884–8.

    CAS  PubMed  Google Scholar 

  24. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001;86(5):1930–5.

    CAS  PubMed  Google Scholar 

  25. Lindsay RS, Funahashi T, Hanson RL, Matsuzawa Y, Tanaka S, Tataranni PA, et al. Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet. 2002;360(9326):57–8.

    CAS  PubMed  Google Scholar 

  26. Iwashima Y, Katsuya T, Ishikawa K, Ouchi N, Ohishi M, Sugimoto K, et al. Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension. 2004;43(6):1318–23.

    CAS  PubMed  Google Scholar 

  27. Ryo M, Nakamura T, Kihara S, Kumada M, Shibazaki S, Takahashi M, et al. Adiponectin as a biomarker of the metabolic syndrome. Circ J. 2004;68(11):975–81.

    CAS  PubMed  Google Scholar 

  28. Kondo H, Shimomura I, Matsukawa Y, Kumada M, Takahashi M, Matsuda M, et al. Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. Diabetes. 2002;51(7):2325–8.

    CAS  PubMed  Google Scholar 

  29. Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N, et al. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol. 2003;23(1):85–9.

    CAS  PubMed  Google Scholar 

  30. Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA. 2004;291(14):1730–7.

    CAS  PubMed  Google Scholar 

  31. 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(5):989–94.

    CAS  PubMed  Google Scholar 

  32. Matsuda M, Tamura R, Kishida N, Segawa T, Kanno K, Nishimoto O, et al. Predictive value of adiponectin in patients with multivessel coronary atherosclerosis detected on computed tomography angiography. J Atheroscler Thromb. 2013;(in press).

  33. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003;423(6941):762–9.

    CAS  PubMed  Google Scholar 

  34. Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M, et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med. 2007;13(3):332–9.

    CAS  PubMed  Google Scholar 

  35. Yamauchi T, Kamon J, Waki H, Imai Y, Shimozawa N, Hioki K, et al. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem. 2003;278(4):2461–8.

    CAS  PubMed  Google Scholar 

  36. Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation. 2000;102(11):1296–301.

    CAS  PubMed  Google Scholar 

  37. Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, et al. 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(5):1723–32.

    CAS  PubMed  Google Scholar 

  38. Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y, et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation. 2001;103(8):1057–63.

    CAS  PubMed  Google Scholar 

  39. Arita Y, Kihara S, Ouchi N, Maeda K, Kuriyama H, Okamoto Y, et al. 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(24):2893–8.

    CAS  PubMed  Google Scholar 

  40. Kumada M, Kihara S, Ouchi N, Kobayashi H, Okamoto Y, Ohashi K, et al. Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation. 2004;109(17):2046–9.

    CAS  PubMed  Google Scholar 

  41. Shibata R, Ouchi N, Ito M, Kihara S, Shiojima I, Pimentel DR, et al. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med. 2004;10(12):1384–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, et al. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med. 2005;11(10):1096–103.

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Fujita K, Maeda N, Sonoda M, Ohashi K, Hibuse T, Nishizawa H, et al. Adiponectin protects against angiotensin II-induced cardiac fibrosis through activation of PPAR-alpha. Arterioscler Thromb Vasc Biol. 2008;28(5):863–70.

    CAS  PubMed  Google Scholar 

  44. Keaney Jr JF, Larson MG, Vasan RS, Wilson PW, Lipinska I, Corey D, et al. Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler Thromb Vasc Biol. 2003;23(3):434–9.

    CAS  PubMed  Google Scholar 

  45. 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(11):1437–42.

    CAS  PubMed  Google Scholar 

  46. Okuno Y, Matsuda M, Kobayashi H, Morita K, Suzuki E, Fukuhara A, et al. Adipose expression of catalase is regulated via a novel remote PPARgamma-responsive region. Biochem Biophys Res Commun. 2008;366(3):698–704.

    CAS  PubMed  Google Scholar 

  47. Okuno Y, Matsuda M, Miyata Y, Fukuhara A, Komuro R, Shimabukuro M, et al. Human catalase gene is regulated by peroxisome proliferator activated receptor-gamma through a response element distinct from that of mouse. Endocr J. 2010;57(4):303–9.

    CAS  PubMed  Google Scholar 

  48. 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(6):E1326–34.

    CAS  PubMed  Google Scholar 

  49. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante Jr AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796–808.

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112(12):1821–30.

    CAS  PubMed Central  PubMed  Google Scholar 

  51. Curzio M, Esterbauer H, Poli G, Biasi F, Cecchini G, Di Mauro C, et al. Possible role of aldehydic lipid peroxidation products as chemoattractants. Int J Tissue React. 1987;9(4):295–306.

    CAS  PubMed  Google Scholar 

  52. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005;54(6):1615–25.

    CAS  PubMed  Google Scholar 

  53. Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, et al. 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(11):1939–45.

    CAS  PubMed  Google Scholar 

  54. Weindruch R, Sohal RS. Seminars in medicine of the Beth Israel Deaconess Medical Center. Caloric intake and aging. N Engl J Med. 1997;337(14):986–94.

    CAS  PubMed Central  PubMed  Google Scholar 

  55. Rebrin I, Kamzalov S, Sohal RS. Effects of age and caloric restriction on glutathione redox state in mice. Free Radic Biol Med. 2003;35(6):626–35.

    CAS  PubMed Central  PubMed  Google Scholar 

  56. Grattagliano I, Portincasa P, Cocco T, Moschetta A, Di Paola M, Palmieri VO, et al. Effect of dietary restriction and N-acetylcysteine supplementation on intestinal mucosa and liver mitochondrial redox status and function in aged rats. Exp Gerontol. 2004;39(9):1323–32.

    CAS  PubMed  Google Scholar 

  57. Cocco T, Sgobbo P, Clemente M, Lopriore B, Grattagliano I, Di Paola M, et al. Tissue-specific changes of mitochondrial functions in aged rats: effect of a long-term dietary treatment with N-acetylcysteine. Free Radic Biol Med. 2005;38(6):796–805.

    CAS  PubMed  Google Scholar 

  58. Houstis N, Rosen ED, Lander ES. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature. 2006;440(7086):944–8.

    CAS  PubMed  Google Scholar 

  59. 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(10):1562–9.

    CAS  PubMed  Google Scholar 

  60. 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(15):10595–602.

    CAS  PubMed  Google Scholar 

  61. 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(3):1006–13.

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Maddux BA, See W, Lawrence Jr JC, 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(2):404–10.

    CAS  PubMed  Google Scholar 

  63. Kaneto H, Kajimoto Y, Miyagawa J, Matsuoka T, Fujitani Y, Umayahara Y, et al. Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity. Diabetes. 1999;48(12):2398–406.

    CAS  PubMed  Google Scholar 

  64. 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(22):2673–8.

    CAS  PubMed  Google Scholar 

  65. Azumi H, Inoue N, Ohashi Y, Terashima M, Mori T, Fujita H, et al. 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(11):1838–44.

    CAS  PubMed  Google Scholar 

  66. Guzik TJ, Sadowski J, Kapelak B, Jopek A, Rudzinski P, Pillai R, et al. Systemic regulation of vascular NAD(P)H oxidase activity and nox isoform expression in human arteries and veins. Arterioscler Thromb Vasc Biol. 2004;24(9):1614–20.

    CAS  PubMed  Google Scholar 

  67. Spiekermann S, Landmesser U, Dikalov S, Bredt M, Gamez G, Tatge H, et al. 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(10):1383–9.

    CAS  PubMed  Google Scholar 

  68. Rajagopalan S, Kurz S, Munzel T, Tarpey M, Freeman BA, Griendling KK, et al. 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(8):1916–23.

    CAS  PubMed Central  PubMed  Google Scholar 

  69. Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res. 2000;86(5):494–501.

    CAS  PubMed  Google Scholar 

  70. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414(6865):813–20.

    CAS  PubMed  Google Scholar 

  71. Jay D, Hitomi H, Griendling KK. Oxidative stress and diabetic cardiovascular complications. Free Radic Biol Med. 2006;40(2):183–92.

    CAS  PubMed  Google Scholar 

  72. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature. 2000;404(6779):787–90.

    CAS  PubMed  Google Scholar 

  73. Sasaki S, Inoguchi T. The role of oxidative stress in the pathogenesis of diabetic vascular complications. Diabetes Metab J. 2012;36(4):255–61.

    PubMed Central  PubMed  Google Scholar 

  74. Basta G, Schmidt AM, De Caterina R. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovasc Res. 2004;63(4):582–92.

    CAS  PubMed  Google Scholar 

  75. Tao L, Gao E, Jiao X, Yuan Y, Li S, Christopher TA, et al. Adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress. Circulation. 2007;115(11):1408–16.

    CAS  PubMed  Google Scholar 

  76. Wang Y, Gao E, Tao L, Lau WB, Yuan Y, Goldstein BJ, et al. AMP-activated protein kinase deficiency enhances myocardial ischemia/reperfusion injury but has minimal effect on the antioxidant/antinitrative protection of adiponectin. Circulation. 2009;119(6):835–44.

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Li R, Wang WQ, Zhang H, Yang X, Fan Q, Christopher TA, et al. 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(6):E1703–8.

    CAS  PubMed  Google Scholar 

  78. Essick EE, Ouchi N, Wilson RM, Ohashi K, Ghobrial J, Shibata R, et al. Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte remodeling. Am J Physiol Heart Circ Physiol. 2011;301(3):H984–93.

    CAS  PubMed  Google Scholar 

  79. Yi W, Sun Y, Gao E, Wei X, Lau WB, Zheng Q, et al. Reduced cardioprotective action of adiponectin in high-fat diet-induced type II diabetic mice and its underlying mechanisms. Antioxid Redox Signal. 2011;15(7):1779–88.

    CAS  PubMed  Google Scholar 

  80. Tsuchida A, Yamauchi T, Ito Y, Hada Y, Maki T, Takekawa S, et al. Insulin/Foxo1 pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity. J Biol Chem. 2004;279(29):30817–22.

    CAS  PubMed  Google Scholar 

  81. Kamada Y, Matsumoto H, Tamura S, Fukushima J, Kiso S, Fukui K, et al. Hypoadiponectinemia accelerates hepatic tumor formation in a nonalcoholic steatohepatitis mouse model. J Hepatol. 2007;47(4):556–64.

    CAS  PubMed  Google Scholar 

  82. Ohashi K, Iwatani H, Kihara S, Nakagawa Y, Komura N, Fujita K, et al. Exacerbation of albuminuria and renal fibrosis in subtotal renal ablation model of adiponectin-knockout mice. Arterioscler Thromb Vasc Biol. 2007;27(9):1910–7.

    CAS  PubMed  Google Scholar 

  83. Koh EH, Park JY, Park HS, Jeon MJ, Ryu JW, Kim M, et al. Essential role of mitochondrial function in adiponectin synthesis in adipocytes. Diabetes. 2007;56(12):2973–81.

    CAS  PubMed  Google Scholar 

  84. Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature. 1990;347(6294):645–50.

    CAS  PubMed  Google Scholar 

  85. Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, et al. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes. 2001;50(9):2094–9.

    CAS  PubMed  Google Scholar 

  86. Iwaki M, Matsuda M, Maeda N, Funahashi T, Matsuzawa Y, Makishima M, et al. Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes. 2003;52(7):1655–63.

    CAS  PubMed  Google Scholar 

  87. Kubota N, Terauchi Y, Kubota T, Kumagai H, Itoh S, Satoh H, et al. Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin-dependent and -independent pathways. J Biol Chem. 2006;281(13):8748–55.

    CAS  PubMed  Google Scholar 

  88. Heo KS, Kim DU, Ryoo S, Nam M, Baek ST, Kim L, et al. 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(4):1017–23.

    CAS  PubMed  Google Scholar 

  89. Lee YS, Kim AY, Choi JW, Kim M, Yasue S, Son HJ, et al. Dysregulation of adipose glutathione peroxidase 3 in obesity contributes to local and systemic oxidative stress. Mol Endocrinol. 2008;22(9):2176–89.

    CAS  PubMed  Google Scholar 

  90. Clasen R, Schupp M, Foryst-Ludwig A, Sprang C, Clemenz M, Krikov M, et al. PPARgamma-activating angiotensin type-1 receptor blockers induce adiponectin. Hypertension. 2005;46(1):137–43.

    CAS  PubMed  Google Scholar 

  91. Hiuge A, Tenenbaum A, Maeda N, Benderly M, Kumada M, Fisman EZ, et al. Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level. Arterioscler Thromb Vasc Biol. 2007;27(3):635–41.

    CAS  PubMed  Google Scholar 

  92. Frederich Jr RC, Kahn BB, Peach MJ, Flier JS. Tissue-specific nutritional regulation of angiotensinogen in adipose tissue. Hypertension. 1992;19(4):339–44.

    CAS  PubMed  Google Scholar 

  93. Goossens GH, Blaak EE, van Baak MA. Possible involvement of the adipose tissue renin-angiotensin system in the pathophysiology of obesity and obesity-related disorders. Obes Rev. 2003;4(1):43–55.

    CAS  PubMed  Google Scholar 

  94. Prasad A, Quyyumi AA. Renin-angiotensin system and angiotensin receptor blockers in the metabolic syndrome. Circulation. 2004;110(11):1507–12.

    PubMed  Google Scholar 

  95. Kurata A, Nishizawa H, Kihara S, Maeda N, Sonoda M, Okada T, et al. Blockade of Angiotensin II type-1 receptor reduces oxidative stress in adipose tissue and ameliorates adipocytokine dysregulation. Kidney Int. 2006;70(10):1717–24.

    CAS  PubMed  Google Scholar 

  96. Tsubouchi H, Inoguchi T, Sonta T, Sato N, Sekiguchi N, Kobayashi K, et al. Statin attenuates high glucose-induced and diabetes-induced oxidative stress in vitro and in vivo evaluated by electron spin resonance measurement. Free Radic Biol Med. 2005;39(4):444–52.

    CAS  PubMed  Google Scholar 

  97. Takagi T, Matsuda M, Abe M, Kobayashi H, Fukuhara A, Komuro R, et al. Effect of pravastatin on the development of diabetes and adiponectin production. Atherosclerosis. 2008;196(1):114–21.

    CAS  PubMed  Google Scholar 

  98. Sugiyama S, Fukushima H, Kugiyama K, Maruyoshi H, Kojima S, Funahashi T, et al. Pravastatin improved glucose metabolism associated with increasing plasma adiponectin in patients with impaired glucose tolerance and coronary artery disease. Atherosclerosis. 2007;194(2):e43–51.

    CAS  PubMed  Google Scholar 

  99. Abe M, Matsuda M, Kobayashi H, Miyata Y, Nakayama Y, Komuro R, et al. Effects of statins on adipose tissue inflammation: their inhibitory effect on MyD88-independent IRF3/IFN-beta pathway in macrophages. Arterioscler Thromb Vasc Biol. 2008;28(5):871–7.

    CAS  PubMed  Google Scholar 

  100. Gervois P, Fruchart JC, Staels B. Drug Insight: mechanisms of action and therapeutic applications for agonists of peroxisome proliferator-activated receptors. Nat Clin Pract Endocrinol Metab. 2007;3(2):145–56.

    CAS  PubMed  Google Scholar 

  101. Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsuzawa Y, Chao CL, et al. Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab. 2001;86(8):3815–9.

    CAS  PubMed  Google Scholar 

  102. Kopp HP, Krzyzanowska K, Mohlig M, Spranger J, Pfeiffer AF, Schernthaner G. Effects of marked weight loss on plasma levels of adiponectin, markers of chronic subclinical inflammation and insulin resistance in morbidly obese women. Int J Obes (Lond). 2005;29(7):766–71.

    CAS  Google Scholar 

  103. Itoh M, Suganami T, Satoh N, Tanimoto-Koyama K, Yuan X, Tanaka M, et al. Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects. Arterioscler Thromb Vasc Biol. 2007;27(9):1918–25.

    CAS  PubMed  Google Scholar 

  104. Neschen S, Morino K, Rossbacher JC, Pongratz RL, Cline GW, Sono S, et al. Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice. Diabetes. 2006;55(4):924–8.

    CAS  PubMed  Google Scholar 

  105. Kusunoki C, Yang L, Yoshizaki T, Nakagawa F, Ishikado A, Kondo M, et al. Omega-3 polyunsaturated fatty acid has an anti-oxidant effect via the Nrf-2/HO-1 pathway in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2013;430(1):225–30.

    CAS  PubMed  Google Scholar 

  106. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369(9567):1090–8.

    CAS  PubMed  Google Scholar 

  107. Yoshida H, Ishikawa T, Suto M, Kurosawa H, Hirowatari Y, Ito K, et al. Effects of supervised aerobic exercise training on serum adiponectin and parameters of lipid and glucose metabolism in subjects with moderate dyslipidemia. J Atheroscler Thromb. 2010;17(11):1160–6.

    CAS  PubMed  Google Scholar 

  108. Ando D, Hosaka Y, Suzuki K, Yamagata Z. Effects of exercise training on circulating high molecular weight adiponectin and adiponectin oligomer composition: a randomized controlled trial. J Atheroscler Thromb. 2009;16(6):733–9.

    CAS  PubMed  Google Scholar 

  109. Simpson KA, Singh MA. Effects of exercise on adiponectin: a systematic review. Obesity (Silver Spring). 2008;16(2):241–56.

    CAS  Google Scholar 

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Correspondence to Morihiro Matsuda.

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Matsuda, M., Shimomura, I. Roles of adiponectin and oxidative stress in obesity-associated metabolic and cardiovascular diseases. Rev Endocr Metab Disord 15, 1–10 (2014). https://doi.org/10.1007/s11154-013-9271-7

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