The Role of Perivascular Fat in Raising Blood Pressure in Obesity and Diabetes

  • Reza AghamohammadzadehEmail author
  • Anthony M. Heagerty
Part of the Updates in Hypertension and Cardiovascular Protection book series (UHCP)


The obesity epidemic has highlighted the need to reassess and fundamentally rethink the pathophysiology of obesity-related hypertension and the interplay between adipocytes, the vasculature and blood glucose homeostasis. In reality, the components of the metabolic syndrome do not exist in isolation, rather in an intricate balance which is ultimately disturbed in disease states. In this chapter, we review the role of adipocytes and the perivascular adipose tissue in health and disease in relation to obesity, hypertension and diabetes.


Adipocytes Adiponectin Hypertension Inflammation Obesity Diabetes Oxidative stress Perivascular adipose tissue Sympathetic nervous system 



Angiotensin converting enzyme


Adipose-derived relaxing factor


5′ Adenosine monophosphate-activated protein kinase


Body mass index


Blood pressure


Central nervous system


Endothelial nitric oxide synthase


Glucose-6-phosphate dehydrogenase


Monocyte chemotactic protein-1


Metabolic syndrome


Mineralocorticoid receptor


Nicotinamide adenine dinucleotide phosphate


Nitric oxide


Nitric oxide synthase


Obstructive sleep apnoea


Palmitic acid methyl ester


Perivascular adipose tissue


Renin-angiotensin-aldosterone system


Reactive oxygen species


Spontaneously hypertensive rat


Sympathetic nervous system


Waist circumference



Sources of Funding: Dr. Aghamohammadzadeh is an NIHR Academic Clinical Lecturer in Cardiology at the University of Manchester.


  1. 1.
    WHO. Obesity and overweight (Factsheet 311). 2016 [updated 2016; cited 04 July 2017].
  2. 2.
    The NHS Information Centre LS. Statistics on Obesity, Physical Activity and Diet: England, 2011. 24 Feb 2011.Google Scholar
  3. 3.
    CDC. U.S. Obesity Trends. 2011 [updated 2011; cited 2011 18 Aug 2011].
  4. 4.
    Neel JV. Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? Am J Hum Genet. 1962;14:353–62.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Diamond J. The double puzzle of diabetes. Nature. 2003;423(6940):599–602.CrossRefPubMedGoogle Scholar
  6. 6.
    Scott EM, Grant PJ. Neel revisited: the adipocyte, seasonality and type 2 diabetes. Diabetologia. 2006;49(7):1462–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Emerging Risk Factors Collaboration, Wormser D, Kaptoge S, Di Angelantonio E, Wood AM, Pennells L, et al. Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies. Lancet. 2011;377(9771):1085–95.CrossRefGoogle Scholar
  8. 8.
    Cornier MA, Despres JP, Davis N, Grossniklaus DA, Klein S, Lamarche B, et al. Assessing adiposity: a scientific statement from the American Heart Association. Circulation. 2011;124:1996–2019.CrossRefGoogle Scholar
  9. 9.
    CDC. Hypertension. 2011 [updated 2011; cited 2011 18 Aug 2011].
  10. 10.
    WHO. Blood pressure. 2017 [updated 2017; cited 2017 04 July 2017].
  11. 11.
    Henry SL, Barzel B, Wood-Bradley RJ, Burke SL, Head GA, Armitage JA. The developmental origins of obesity-related hypertension. Clin Exp Pharmacol Physiol. 2012;39:799–806.CrossRefPubMedGoogle Scholar
  12. 12.
    Kotchen TA. Obesity-related hypertension: epidemiology, pathophysiology, and clinical management. Am J Hypertens. 2010;23(11):1170–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Gosmanov AR, Smiley DD, Robalino G, Siquiera J, Khan B, Le NA, et al. Effects of oral and intravenous fat load on blood pressure, endothelial function, sympathetic activity, and oxidative stress in obese healthy subjects. Am J Physiol Endocrinol Metab. 2010;299(6):E953–8.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Dobrian AD, Schriver SD, Lynch T, Prewitt RL. Effect of salt on hypertension and oxidative stress in a rat model of diet-induced obesity. Am J Physiol Ren Physiol. 2003;285(4):F619–28.CrossRefGoogle Scholar
  15. 15.
    Aghamohammadzadeh R, Unwin RD, Greenstein AS, Heagerty AM. Effects of obesity on perivascular adipose tissue vasorelaxant function: nitric oxide, inflammation and elevated systemic blood pressure. J Vasc Res. 2015;52(5):299–305.CrossRefPubMedGoogle Scholar
  16. 16.
    Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007;116(1):39–48.CrossRefPubMedGoogle Scholar
  17. 17.
    Gesta S, Tseng YH, Kahn CR. Developmental origin of fat: tracking obesity to its source. Cell. 2007;131(2):242–56.CrossRefPubMedGoogle Scholar
  18. 18.
    Manolopoulos KN, Karpe F, Frayn KN. Gluteofemoral body fat as a determinant of metabolic health. Int J Obes. 2010;34(6):949–59.CrossRefGoogle Scholar
  19. 19.
    Chatterjee TK, Stoll LL, Denning GM, Harrelson A, Blomkalns AL, Idelman G, et al. Proinflammatory phenotype of perivascular adipocytes: influence of high-fat feeding. Circ Res. 2009;104(4):541–9.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Dorresteijn JA, Visseren FL, Spiering W. Mechanisms linking obesity to hypertension. Obes Rev. 2011;13:17–26.CrossRefPubMedGoogle Scholar
  21. 21.
    Lee CM, Huxley RR, Wildman RP, Woodward M. Indices of abdominal obesity are better discriminators of cardiovascular risk factors than BMI: a meta-analysis. J Clin Epidemiol. 2008;61(7):646–53.CrossRefPubMedGoogle Scholar
  22. 22.
    Iacobellis G, Assael F, Ribaudo MC, Zappaterreno A, Alessi G, Di Mario U, et al. Epicardial fat from echocardiography: a new method for visceral adipose tissue prediction. Obes Res. 2003;11(2):304–10.CrossRefPubMedGoogle Scholar
  23. 23.
    Iacobellis G, Ribaudo MC, Assael F, Vecci E, Tiberti C, Zappaterreno A, et al. Echocardiographic epicardial adipose tissue is related to anthropometric and clinical parameters of metabolic syndrome: a new indicator of cardiovascular risk. J Clin Endocrinol Metab. 2003;88(11):5163–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Iacobellis G, Willens HJ, Barbaro G, Sharma AM. Threshold values of high-risk echocardiographic epicardial fat thickness. Obesity (Silver Spring). 2008;16(4):887–92.CrossRefGoogle Scholar
  25. 25.
    Simons PJ, van den Pangaart PS, Aerts JM, Boon L. Pro-inflammatory delipidizing cytokines reduce adiponectin secretion from human adipocytes without affecting adiponectin oligomerization. J Endocrinol. 2007;192(2):289–99.CrossRefPubMedGoogle Scholar
  26. 26.
    Baker AR, Silva NF, Quinn DW, Harte AL, Pagano D, Bonser RS, et al. Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease. Cardiovasc Diabetol. 2006;5:1.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Eiras S, Teijeira-Fernandez E, Shamagian LG, Fernandez AL, Vazquez-Boquete A, Gonzalez-Juanatey JR. Extension of coronary artery disease is associated with increased IL-6 and decreased adiponectin gene expression in epicardial adipose tissue. Cytokine. 2008;43(2):174–80.CrossRefPubMedGoogle Scholar
  28. 28.
    Iacobellis G, Pistilli D, Gucciardo M, Leonetti F, Miraldi F, Brancaccio G, et al. Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease. Cytokine. 2005;29(6):251–5.PubMedGoogle Scholar
  29. 29.
    Iacobellis G, di Gioia CR, Cotesta D, Petramala L, Travaglini C, De Santis V, et al. Epicardial adipose tissue adiponectin expression is related to intracoronary adiponectin levels. Horm Metab Res. 2009;41(3):227–31.CrossRefPubMedGoogle Scholar
  30. 30.
    Teijeira-Fernandez E, Eiras S, Grigorian-Shamagian L, Fernandez A, Adrio B, Gonzalez-Juanatey JR. Epicardial adipose tissue expression of adiponectin is lower in patients with hypertension. J Hum Hypertens. 2008;22(12):856–63.CrossRefPubMedGoogle Scholar
  31. 31.
    Ohashi K, Kihara S, Ouchi N, Kumada M, Fujita K, Hiuge A, et al. Adiponectin replenishment ameliorates obesity-related hypertension. Hypertension. 2006;47(6):1108–16.CrossRefPubMedGoogle Scholar
  32. 32.
    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.CrossRefPubMedGoogle Scholar
  33. 33.
    Yudkin JS, Eringa E, Stehouwer CD. “Vasocrine” signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease. Lancet. 2005;365(9473):1817–20.CrossRefPubMedGoogle Scholar
  34. 34.
    Soltis EE, Cassis LA. Influence of perivascular adipose tissue on rat aortic smooth muscle responsiveness. Clin Exp Hypertens A. 1991;13(2):277–96.PubMedGoogle Scholar
  35. 35.
    Gao YJ, Lu C, Su LY, Sharma AM, Lee RM. Modulation of vascular function by perivascular adipose tissue: the role of endothelium and hydrogen peroxide. Br J Pharmacol. 2007;151(3):323–31.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Galvez-Prieto B, Bolbrinker J, Stucchi P, de Las Heras AI, Merino B, Arribas S, et al. Comparative expression analysis of the renin-angiotensin system components between white and brown perivascular adipose tissue. J Endocrinol. 2008;197(1):55–64.CrossRefPubMedGoogle Scholar
  37. 37.
    Lu C, Su LY, Lee RM, Gao YJ. Alterations in perivascular adipose tissue structure and function in hypertension. Eur J Pharmacol. 2011;656(1-3):68–73.CrossRefPubMedGoogle Scholar
  38. 38.
    Dubrovska G, Verlohren S, Luft FC, Gollasch M. Mechanisms of ADRF release from rat aortic adventitial adipose tissue. Am J Physiol Heart Circ Physiol. 2004;286(3):H1107–13.CrossRefPubMedGoogle Scholar
  39. 39.
    Deng G, Long Y, Yu YR, Li MR. Adiponectin directly improves endothelial dysfunction in obese rats through the AMPK-eNOS Pathway. Int J Obes. 2010;34(1):165–71.CrossRefGoogle Scholar
  40. 40.
    Yilmaz MI, Sonmez A, Caglar K, Celik T, Yenicesu M, Eyileten T, et al. Effect of antihypertensive agents on plasma adiponectin levels in hypertensive patients with metabolic syndrome. Nephrology (Carlton). 2007;12(2):147–53.CrossRefGoogle Scholar
  41. 41.
    Fesus G, Dubrovska G, Gorzelniak K, Kluge R, Huang Y, Luft FC, et al. Adiponectin is a novel humoral vasodilator. Cardiovasc Res. 2007;75(4):719–27.CrossRefPubMedGoogle Scholar
  42. 42.
    Greenstein AS, Khavandi K, Withers SB, Sonoyama K, Clancy O, Jeziorska M, et al. Local inflammation and hypoxia abolish the protective anticontractile properties of perivascular fat in obese patients. Circulation. 2009;119(12):1661–70.CrossRefPubMedGoogle Scholar
  43. 43.
    Aghamohammadzadeh R, Withers SB, Lynch FM, Greenstein AS, Malik R, Heagerty AM. Perivascular adipose tissue from human systemic and coronary vessels: the emergence of a new pharmacotherapeutic target. Br J Pharmacol. 2012;165:670–82.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Chen H, Montagnani M, Funahashi T, Shimomura I, Quon MJ. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem. 2003;278(45):45021–6.CrossRefPubMedGoogle Scholar
  45. 45.
    Aghamohammadzadeh R, Greenstein AS, Yadav R, Jeziorska M, Hama S, Soltani F, et al. The effects of bariatric surgery on human small artery function: evidence for reduction in perivascular adipocyte inflammation, and the restoration of normal anticontractile activity despite persistent obesity. J Am Coll Cardiol. 2013;62:128–35.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Kang YE, Kim JM, Joung KH, Lee JH, You BR, Choi MJ, et al. The roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in obesity-associated insulin resistance in modest obesity and early metabolic dysfunction. PLoS One. 2016;11(4):e0154003.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Qiao YC, Shen J, He L, Hong XZ, Tian F, Pan YH, et al. Changes of regulatory T cells and of proinflammatory and immunosuppressive cytokines in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. J Diabetes Res. 2016;2016:3694957.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Kim KY, Kim JK, Jeon JH, Yoon SR, Choi I, Yang Y. c-Jun N-terminal kinase is involved in the suppression of adiponectin expression by TNF-alpha in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2005;327(2):460–7.CrossRefPubMedGoogle Scholar
  49. 49.
    Lee JM, Kim SR, Yoo SJ, Hong OK, Son HS, Chang SA. The relationship between adipokines, metabolic parameters and insulin resistance in patients with metabolic syndrome and type 2 diabetes. J Int Med Res. 2009;37(6):1803–12.CrossRefPubMedGoogle Scholar
  50. 50.
    Lee S, Zhang H, Chen J, Dellsperger KC, Hill MA, Zhang C. Adiponectin abates diabetes-induced endothelial dysfunction by suppressing oxidative stress, adhesion molecules, and inflammation in type 2 diabetic mice. Am J Physiol Heart Circ Physiol. 2012;303(1):H106–15.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Nacci C, Leo V, De Benedictis L, Potenza MA, Sgarra L, De Salvia MA, et al. Infliximab therapy restores adiponectin expression in perivascular adipose tissue and improves endothelial nitric oxide-mediated vasodilation in mice with type 1 diabetes. Vasc Pharmacol. 2016;87:83–91.CrossRefGoogle Scholar
  52. 52.
    Lu C, Zhao AX, Gao YJ, Lee RM. Modulation of vein function by perivascular adipose tissue. Eur J Pharmacol. 2011;657(1-3):111–6.CrossRefPubMedGoogle Scholar
  53. 53.
    Lee RM, Bader M, Alenina N, Santos RA, Gao YJ, Lu C. Mas receptors in modulating relaxation induced by perivascular adipose tissue. Life Sci. 2011;89:467–72.CrossRefPubMedGoogle Scholar
  54. 54.
    Byku M, Macarthur H, Westfall TC. Inhibitory effects of angiotensin (1-7) on the nerve stimulation-induced release of norepinephrine and neuropeptide y from the mesenteric arterial bed. Am J Physiol Heart Circ Physiol. 2009;289:H457–65.Google Scholar
  55. 55.
    Marques FD, Ferreira AJ, Sinisterra RD, Jacoby BA, Sousa FB, Caliari MV, et al. An oral formulation of angiotensin-(1-7) produces cardioprotective effects in infarcted and isoproterenol-treated rats. Hypertension. 2011;57(3):477–83.CrossRefPubMedGoogle Scholar
  56. 56.
    Ribiere C, Jaubert AM, Gaudiot N, Sabourault D, Marcus ML, Boucher JL, et al. White adipose tissue nitric oxide synthase: a potential source for NO production. Biochem Biophys Res Commun. 1996;222(3):706–12.CrossRefPubMedGoogle Scholar
  57. 57.
    Gil-Ortega M, Stucchi P, Guzman-Ruiz R, Cano V, Arribas S, Gonzalez MC, et al. Adaptative nitric oxide overproduction in perivascular adipose tissue during early diet-induced obesity. Endocrinology. 2010;151:3299–306.CrossRefPubMedGoogle Scholar
  58. 58.
    Ribiere C, Jaubert AM, Sabourault D, Lacasa D, Giudicelli Y. Insulin stimulates nitric oxide production in rat adipocytes. Biochem Biophys Res Commun. 2002;291(2):394–9.CrossRefPubMedGoogle Scholar
  59. 59.
    Mehebik N, Jaubert AM, Sabourault D, Giudicelli Y, Ribiere C. Leptin-induced nitric oxide production in white adipocytes is mediated through PKA and MAP kinase activation. Am J Phys Cell Physiol. 2005;289(2):C379–87.CrossRefGoogle Scholar
  60. 60.
    Rahmouni K, Correia ML, Haynes WG, Mark AL. Obesity-associated hypertension: new insights into mechanisms. Hypertension. 2005;45(1):9–14.CrossRefPubMedGoogle Scholar
  61. 61.
    Mark AL, Shaffer RA, Correia ML, Morgan DA, Sigmund CD, Haynes WG. Contrasting blood pressure effects of obesity in leptin-deficient ob/ob mice and agouti yellow obese mice. J Hypertens. 1999;17(12 Pt 2):1949–53.CrossRefPubMedGoogle Scholar
  62. 62.
    da Silva AA, do Carmo J, Dubinion J, Hall JE. The role of the sympathetic nervous system in obesity-related hypertension. Curr Hypertens Rep. 2009;11(3):206–11.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Schleifenbaum J, Kohn C, Voblova N, Dubrovska G, Zavarirskaya O, Gloe T, et al. Systemic peripheral artery relaxation by KCNQ channel openers and hydrogen sulfide. J Hypertens. 2010;28(9):1875–82.CrossRefPubMedGoogle Scholar
  64. 64.
    Lee YC, Chang HH, Chiang CL, Liu CH, Yeh JI, Chen MF, et al. Role of perivascular adipose tissue-derived methyl palmitate in vascular tone regulation and pathogenesis of hypertension. Circulation. 2011;124:1160–71.CrossRefPubMedGoogle Scholar
  65. 65.
    Withers BS, Agabiti-Rosei C, Linvingstone DM, Little MC, Aslam R, Malik RA, et al. Macrophage activation is responsible for loss of anticontractile function in inflamed perivascular fat. Arterioscler Thromb Vasc Biol. 2011;31:908–13.CrossRefPubMedGoogle Scholar
  66. 66.
    Withers SB, Forman R, Meza-Perez S, Sorobetea D, Sitnik K, Hopwood T, et al. Eosinophils are key regulators of perivascular adipose tissue and vascular functionality. Sci Rep. 2017 Mar 17;7:44571.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Fitzgibbons TP, Kogan S, Aouadi M, Hendricks GM, Straubhaar J, Czech MP. Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation. Am J Physiol Heart Circ Physiol. 2011;301(4):H1425–37.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest. 2006;116(6):1494–505.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Kim CS, Park HS, Kawada T, Kim JH, Lim D, Hubbard NE, et al. Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes. 2006;30(9):1347–55.CrossRefGoogle Scholar
  70. 70.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Shah R, Hinkle CC, Ferguson JF, Mehta NN, Li M, Qu L, et al. Fractalkine is a novel human adipochemokine associated with type 2 diabetes. Diabetes. 2011;60(5):1512–8.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Sirois-Gagnon D, Chamberland A, Perron S, Brisson D, Gaudet D, Laprise C. Association of common polymorphisms in the fractalkine receptor (CX3CR1) with obesity. Obesity (Silver Spring). 2010;19(1):222–7.CrossRefGoogle Scholar
  73. 73.
    Timofeeva AV, Goryunova LE, Khaspekov GL, Kovalevskii DA, Scamrov AV, Bulkina OS, et al. Altered gene expression pattern in peripheral blood leukocytes from patients with arterial hypertension. Ann N Y Acad Sci. 2006;1091:319–35.CrossRefPubMedGoogle Scholar
  74. 74.
    Sell H, Laurencikiene J, Taube A, Eckardt K, Cramer A, Horrighs A, et al. Chemerin is a novel adipocyte-derived factor inducing insulin resistance in primary human skeletal muscle cells. Diabetes. 2009;58(12):2731–40.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Ouwens DM, Bekaert M, Lapauw B, Van Nieuwenhove Y, Lehr S, Hartwig S, et al. Chemerin as biomarker for insulin sensitivity in males without typical characteristics of metabolic syndrome. Arch Physiol Biochem. 2012;118(3):135–8.CrossRefPubMedGoogle Scholar
  76. 76.
    Schipper HS, Nuboer R, Prop S, van den Ham HJ, de Boer FK, Kesmir C, et al. Systemic inflammation in childhood obesity: circulating inflammatory mediators and activated CD14++ monocytes. Diabetologia. 2012;55(10):2800–10.CrossRefPubMedGoogle Scholar
  77. 77.
    Verrijn Stuart AA, Schipper HS, Tasdelen I, Egan DA, Prakken BJ, Kalkhoven E, et al. Altered plasma adipokine levels and in vitro adipocyte differentiation in pediatric type 1 diabetes. J Clin Endocrinol Metab. 2011;97(2):463–72.CrossRefPubMedGoogle Scholar
  78. 78.
    Kunimoto H, Kazama K, Takai M, Oda M, Okada M, Yamawaki H. Chemerin promotes the proliferation and migration of vascular smooth muscle and increases mouse blood pressure. Am J Physiol Heart Circ Physiol. 2015;309(5):H1017–28.PubMedGoogle Scholar
  79. 79.
    Ferland DJ, Darios ES, Neubig RR, Sjogren B, Truong N, Torres R, et al. Chemerin-induced arterial contraction is Gi- and calcium-dependent. Vasc Pharmacol. 2017;88:30–41.CrossRefGoogle Scholar
  80. 80.
    Shin H-Y, Lee DC, Chu SH, Jeon JY, Lee MK, Im JA, et al. Chemerin levels are positively correlated with abdominal visceral fat accumulation. Clin Endocrinol. 2012;77(1):47–50.CrossRefGoogle Scholar
  81. 81.
    Chakaroun R, Raschpichler M, Kloting N, Oberbach A, Flehmig G, Kern M, et al. Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity. Metabolism. 2011;61(5):706–14.CrossRefPubMedGoogle Scholar
  82. 82.
    Sell H, Divoux A, Poitou C, Basdevant A, Bouillot JL, Bedossa P, et al. Chemerin correlates with markers for fatty liver in morbidly obese patients and strongly decreases after weight loss induced by bariatric surgery. J Clin Endocrinol Metab. 2010;95(6):2892–6.CrossRefPubMedGoogle Scholar
  83. 83.
    Landgraf K, Friebe D, Ullrich T, Kratzsch J, Dittrich K, Herberth G, et al. Chemerin as a mediator between obesity and vascular inflammation in children. J Clin Endocrinol Metab. 2012;97(4):E556–64.CrossRefPubMedGoogle Scholar
  84. 84.
    Van Harmelen V, Ariapart P, Hoffstedt J, Lundkvist I, Bringman S, Arner P. Increased adipose angiotensinogen gene expression in human obesity. Obesity. 2000;8(4):337–41.CrossRefGoogle Scholar
  85. 85.
    Engeli S, Negrel R, Sharma AM. Physiology and pathophysiology of the adipose tissue renin-angiotensin system. Hypertension. 2000;35(6):1270–7.CrossRefPubMedGoogle Scholar
  86. 86.
    Goodfriend TL, Calhoun DA. Resistant hypertension, obesity, sleep apnea, and aldosterone: theory and therapy. Hypertension. 2004;43(3):518–24.CrossRefPubMedGoogle Scholar
  87. 87.
    Goodfriend TL, Egan BM, Kelley DE. Aldosterone in obesity. Endocr Res. 1998;24(3-4):789–96.CrossRefPubMedGoogle Scholar
  88. 88.
    Goodfriend TL, Kelley DE, Goodpaster BH, Winters SJ. Visceral obesity and insulin resistance are associated with plasma aldosterone levels in women. Obes Res. 1999;7(4):355–62.CrossRefPubMedGoogle Scholar
  89. 89.
    Maron BA, Zhang YY, Handy DE, Beuve A, Tang SS, Loscalzo J, et al. Aldosterone increases oxidant stress to impair guanylyl cyclase activity by cysteinyl thiol oxidation in vascular smooth muscle cells. J Biol Chem. 2009;284(12):7665–72.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Wang H, Shimosawa T, Matsui H, Kaneko T, Ogura S, Uetake Y, et al. Paradoxical mineralocorticoid receptor activation and left ventricular diastolic dysfunction under high oxidative stress conditions. J Hypertens. 2008;26(7):1453–62.CrossRefPubMedGoogle Scholar
  91. 91.
    Leopold JA, Dam A, Maron BA, Scribner AW, Liao R, Handy DE, et al. Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity. Nat Med. 2007;13(2):189–97.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Maron BA, Leopold JA. Aldosterone receptor antagonists: effective but often forgotten. Circulation. 2010;121(7):934–9.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Guo C, Ricchiuti V, Lian BQ, Yao TM, Coutinho P, Romero JR, et al. Mineralocorticoid receptor blockade reverses obesity-related changes in expression of adiponectin, peroxisome proliferator-activated receptor-gamma, and proinflammatory adipokines. Circulation. 2008;117(17):2253–61.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    de Paula RB, da Silva AA, Hall JE. Aldosterone antagonism attenuates obesity-induced hypertension and glomerular hyperfiltration. Hypertension. 2004;43(1):41–7.CrossRefPubMedGoogle Scholar
  95. 95.
    Rahmouni K, Barthelmebs M, Grima M, Imbs JL, De Jong W. Involvement of brain mineralocorticoid receptor in salt-enhanced hypertension in spontaneously hypertensive rats. Hypertension. 2001;38(4):902–6.CrossRefPubMedGoogle Scholar
  96. 96.
    Vaziri ND, Ni Z, Oveisi F, Trnavsky-Hobbs DL. Effect of antioxidant therapy on blood pressure and NO synthase expression in hypertensive rats. Hypertension. 2000;36(6):957–64.CrossRefPubMedGoogle Scholar
  97. 97.
    Drummond GR, Selemidis S, Griendling KK, Sobey CG. Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Nat Rev Drug Discov. 2011;10(6):453–71.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Safar ME, Czernichow S, Blacher J. Obesity, arterial stiffness, and cardiovascular risk. J Am Soc Nephrol. 2006;17(4 Suppl 2):S109–11.CrossRefPubMedGoogle Scholar
  99. 99.
    Singhal A, Farooqi IS, Cole TJ, O’Rahilly S, Fewtrell M, Kattenhorn M, et al. Influence of leptin on arterial distensibility: a novel link between obesity and cardiovascular disease? Circulation. 2002;106(15):1919–24.CrossRefPubMedGoogle Scholar
  100. 100.
    Kotsis V, Stabouli S, Papakatsika S, Rizos Z, Parati G. Mechanisms of obesity-induced hypertension. Hypertens Res. 2010;33(5):386–93.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Jin RC, Loscalzo J. Vascular nitric oxide: formation and function. J Blood Med. 2010;2010(1):147–62.PubMedGoogle Scholar
  102. 102.
    Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342(19):1378–84.CrossRefGoogle Scholar
  103. 103.
    Wolk R, Shamsuzzaman AS, Somers VK. Obesity, sleep apnea, and hypertension. Hypertension. 2003;42(6):1067–74.CrossRefPubMedGoogle Scholar
  104. 104.
    Yang R, Sikka G, Larson J, Watts VL, Niu X, Ellis CL, et al. Restoring leptin signaling reduces hyperlipidemia and improves vascular stiffness induced by chronic intermittent hypoxia. Am J Physiol Heart Circ Physiol. 2011;300(4):H1467–76.CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Rumantir MS, Vaz M, Jennings GL, Collier G, Kaye DM, Seals DR, et al. Neural mechanisms in human obesity-related hypertension. J Hypertens. 1999;17(8):1125–33.CrossRefPubMedGoogle Scholar
  106. 106.
    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(7):978–86.CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Gao YJ, Takemori K, Su LY, An WS, Lu C, Sharma AM, et al. Perivascular adipose tissue promotes vasoconstriction: the role of superoxide anion. Cardiovasc Res. 2006;71(2):363–73.CrossRefPubMedGoogle Scholar
  108. 108.
    Lu C, Su LY, Lee RM, Gao YJ. Mechanisms for perivascular adipose tissue-mediated potentiation of vascular contraction to perivascular neuronal stimulation: the role of adipocyte-derived angiotensin II. Eur J Pharmacol. 2011;634(1-3):107–12.CrossRefGoogle Scholar
  109. 109.
    Butner KL, Nickols-Richardson SM, Clark SF, Ramp WK, Herbert WG. A review of weight loss following Roux-en-Y gastric bypass vs restrictive bariatric surgery: impact on adiponectin and insulin. Obes Surg. 2010;20(5):559–68.CrossRefPubMedGoogle Scholar
  110. 110.
    Compher C, Badellino KO. Obesity and inflammation: lessons from bariatric surgery. JPEN J Parenter Enteral Nutr. 2008;32(6):645–7.CrossRefPubMedGoogle Scholar
  111. 111.
    Ibrahim MM. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev. 2009;11(1):11–8.CrossRefPubMedGoogle Scholar
  112. 112.
    Forsythe LK, Wallace JM, Livingstone MB. Obesity and inflammation: the effects of weight loss. Nutr Res Rev. 2008;21(2):117–33.CrossRefPubMedGoogle Scholar
  113. 113.
    Moschen AR, Molnar C, Geiger S, Graziadei I, Ebenbichler CF, Weiss H, et al. Anti-inflammatory effects of excessive weight loss: potent suppression of adipose interleukin 6 and tumour necrosis factor {alpha} expression. Gut. 2010;59:1259–64.CrossRefPubMedGoogle Scholar
  114. 114.
    Blackburn GL, Wollner SB, Jones DB. Bariatric surgery as treatment for type 2 diabetes. Curr Diab Rep. 2010;10(4):261–3.CrossRefPubMedGoogle Scholar
  115. 115.
    Wong KE, Szeto FL, Zhang W, Ye H, Kong J, Zhang Z, et al. Involvement of the vitamin D receptor in energy metabolism: regulation of uncoupling proteins. Am J Physiol Endocrinol Metab. 2009;296(4):E820–8.CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Wong KE, Kong J, Zhang W, Szeto FL, Ye H, Deb DK, et al. Targeted expression of human vitamin D receptor in adipocytes decreases energy expenditure and induces obesity in mice. J Biol Chem. 2011;286:33804–10.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Cardiovascular SciencesThe University of ManchesterManchesterUK

Personalised recommendations