Human obesity and endothelium-dependent responsiveness

British Journal of Pharmacology

Volumn 165, Issue 3, 2012, Pages 561-573

  Campia, Umberto ^a   Tesauro, Manfredi ^b   Cardillo, Carmine ^c  

^a NORTHWESTERN UNIVERSITY   (United States)

^b UNIVERSITY OF ROME TOR VERGATA   (Italy)

^c CATHOLIC UNIVERSITY   (Italy)

Author keywords

endothelium; metabolic syndrome; Obesity; oxidative stress; vasodilation

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ADIPOCYTOKINE; ANGIOTENSIN RECEPTOR ANTAGONIST; ENDOTHELIAL NITRIC OXIDE SYNTHASE; ENDOTHELIN 1; FATTY ACID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INSULIN; IRBESARTAN; METFORMIN; NITRIC OXIDE; PHOSPHATIDYLINOSITOL 3 KINASE; PIOGLITAZONE; PLACEBO; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; RESVERATROL; ROSIGLITAZONE; TETRAHYDROLIPSTATIN; THIOCTIC ACID; TUMOR NECROSIS FACTOR ALPHA; XANTHINE OXIDASE;

ADIPOSE TISSUE; ATHEROSCLEROTIC PLAQUE; BLOOD VESSEL TONE; CALORIC RESTRICTION; CARDIOVASCULAR DISEASE; CHRONIC INFLAMMATION; CYTOKINE RELEASE; DIARRHEA; DYSLIPIDEMIA; EDEMA; ENDOTHELIAL DYSFUNCTION; EXERCISE; GASTROINTESTINAL SYMPTOM; GLUCOSE TRANSPORT; HUMAN; HYPERINSULINEMIA; INSULIN RESISTANCE; LIPID STORAGE; METABOLIC SYNDROME X; NAUSEA AND VOMITING; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; OXIDATIVE STRESS; PRIORITY JOURNAL; REVIEW; VASCULAR DISEASE; VASCULAR ENDOTHELIUM; VASCULAR SMOOTH MUSCLE; VASODILATATION; WEIGHT REDUCTION;

ADIPOSE TISSUE; ANIMALS; ENDOTHELIN-1; ENDOTHELIUM, VASCULAR; HUMANS; INSULIN; OBESITY; VASODILATION;

EID: 84855682698     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2011.01661.x     Document Type: Review

References (131)

1. de Aguiar LG, Bahia LR, Villela N, Laflor C, Sicuro F, Wiernsperger N, et al,. (2006). Metformin improves endothelial vascular reactivity in first-degree relatives of type 2 diabetic patients with metabolic syndrome and normal glucose tolerance. Diabetes Care 29: 1083-1089. (Pubitemid 44115248)
2. Ahima RS, Flier JS, (2000). Leptin. Annu Rev Physiol 62: 413-437. (Pubitemid 30618269)
3. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al,. (2009). Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120: 1640-1645.
4. Arslanian S, (2002). Type 2 diabetes in children: clinical aspects and risk factors. Horm Res 57 (Suppl. 1): 19-28. (Pubitemid 34458077)
5. Ayyad C, Andersen T, (2000). Long-term efficacy of dietary treatment of obesity: a systematic review of studies published between 1931 and 1999. Obes Rev 1: 113-119.
6. Baron AD, Clark MG, (1997). Role of blood flow in the regulation of muscle glucose uptake. Annu Rev Nutr 17: 487-499. (Pubitemid 27328810)
7. Baron AD, Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, (1995). Insulin-mediated skeletal muscle vasodilation contributes to both insulin sensitivity and responsiveness in lean humans. J Clin Invest 96: 786-792.
8. Baur JA, Sinclair DA, (2006). Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5: 493-506. (Pubitemid 44136961)
9. Bendall JK, Alp NJ, Warrick N, Cai S, Adlam D, Rockett K, et al,. (2005). Stoichiometric relationships between endothelial tetrahydrobiopterin, endothelial NO synthase (eNOS) activity, and eNOS coupling in vivo: insights from transgenic mice with endothelial-targeted GTP cyclohydrolase 1 and eNOS overexpression. Circ Res 97: 864-871. (Pubitemid 41552671)
10. Berenson GS, Srinivasan SR, Bao W, Newman WP 3rd, Tracy RE, Wattigney WA, (1998). Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med 338: 1650-1656. (Pubitemid 28267909)
11. Bevilacqua S, Bonadonna R, Buzzigoli G, Boni C, Ciociaro D, Maccari F, et al,. (1987). Acute elevation of free fatty acid levels leads to hepatic insulin resistance in obese subjects. Metabolism 36: 502-506. (Pubitemid 17072120)
12. Bigornia SJ, Mott MM, Hess DT, Apovian CM, McDonnell ME, Duess MA, et al,. (2010). Long-term successful weight loss improves vascular endothelial function in severely obese individuals. Obesity (Silver Spring) 18: 754-759.
13. Bjorntorp P, (1990). 'Portal' adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10: 493-496. (Pubitemid 20220571)
14. Bjorntorp P, (1991). Metabolic implications of body fat distribution. Diabetes Care 14: 1132-1143.
15. Bornstein SR, Ehrhart-Bornstein M, Wong ML, Licinio J, (2008). Is the worldwide epidemic of obesity a communicable feature of globalization? Exp Clin Endocrinol Diabetes 116 (Suppl. 1): S30-S32.
16. Bouchard C, Despres JP, Mauriege P, (1993). Genetic and nongenetic determinants of regional fat distribution. Endocr Rev 14: 72-93. (Pubitemid 23066533)
17. Bradley EA, Eringa EC, Stehouwer CD, Korstjens I, Amerongen GP, Musters R, et al,. (2010). Activation of AMP-activated protein kinase by 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside in the muscle microcirculation increases nitric oxide synthesis and microvascular perfusion. Arterioscler Thromb Vasc Biol 30: 1137-1142.
18. Brook RD, Bard RL, Glazewski L, Kehrer C, Bodary PF, Eitzman DL, et al,. (2004). Effect of short-term weight loss on the metabolic syndrome and conduit vascular endothelial function in overweight adults. Am J Cardiol 93: 1012-1016. (Pubitemid 38479456)
19. Brooks CL, Gu W, (2009). How does SIRT1 affect metabolism, senescence and cancer? Nat Rev Cancer 9: 123-128.
20. Cai H, Harrison DG, (2000). Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 87: 840-844.
21. Campia U, Matuskey LA, Panza JA, (2006). Peroxisome proliferator- activated receptor-gamma activation with pioglitazone improves endothelium-dependent dilation in nondiabetic patients with major cardiovascular risk factors. Circulation 113: 867-875.
22. Caprio S, (2002). Insulin resistance in childhood obesity. J Pediatr Endocrinol Metab 15 (Suppl. 1): 487-492. (Pubitemid 34704756)
23. Cardillo C, Kilcoyne CM, Nambi SS, Cannon RO 3rd, Quon MJ, Panza JA, (1998). Vasodilator response to systemic but not to local hyperinsulinemia in the human forearm. Hypertension 32: 740-745. (Pubitemid 28480554)
24. Cardillo C, Nambi SS, Kilcoyne CM, Choucair WK, Katz A, Quon MJ, et al,. (1999). Insulin stimulates both endothelin and nitric oxide activity in the human forearm. Circulation 100: 820-825. (Pubitemid 29398879)
25. Cardillo C, Campia U, Iantorno M, Panza JA, (2004). Enhanced vascular activity of endogenous endothelin-1 in obese hypertensive patients. Hypertension 43: 36-40. (Pubitemid 38031908)
26. Carey VJ, Walters EE, Colditz GA, Solomon CG, Willett WC, Rosner BA, et al,. (1997). Body fat distribution and risk of non-insulin-dependent diabetes mellitus in women. The Nurses' Health Study. Am J Epidemiol 145: 614-619. (Pubitemid 27154864)
27. Cassano PA, Segal MR, Vokonas PS, Weiss ST, (1990). Body fat distribution, blood pressure, and hypertension. A prospective cohort study of men in the normative aging study. Ann Epidemiol 1: 33-48.
28. Chan JM, Rimm EB, Colditz GA, Stampfer MJ, Willett WC, (1994). Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care 17: 961-969. (Pubitemid 24268605)
29. Chen H, Montagnani M, Funahashi T, Shimomura I, Quon MJ, (2003). Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem 278: 45021-45026. (Pubitemid 37377262)
30. Chiarugi P, Fiaschi T, (2010). Adiponectin in health and diseases: from metabolic syndrome to tissue regeneration. Expert Opin Ther Targets 14: 193-206.
31. Clark MG, Wallis MG, Barrett EJ, Vincent MA, Richards SM, Clerk LH, et al,. (2003). Blood flow and muscle metabolism: a focus on insulin action. Am J Physiol Endocrinol Metab 284: E241-E258. (Pubitemid 36120096)
32. Cusi K, Maezono K, Osman A, Pendergrass M, Patti ME, Pratipanawatr T, et al,. (2000). Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. J Clin Invest 105: 311-320. (Pubitemid 30094451)
33. Dandona P, Dhindsa S, Ghanim H, Chaudhuri A, (2007). Angiotensin II and inflammation: the effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade. J Hum Hypertens 21: 20-27. (Pubitemid 44921816)
34. Davis BJ, Xie Z, Viollet B, Zou MH, (2006). Activation of the AMP-activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase. Diabetes 55: 496-505. (Pubitemid 43343281)
35. De Keulenaer GW, Alexander RW, Ushio-Fukai M, Ishizaka N, Griendling KK, (1998). Tumour necrosis factor alpha activates a p22phox-based NADH oxidase in vascular smooth muscle. Biochem J 329: 653-657.
36. Djaberi R, Schuijf JD, van Werkhoven JM, Nucifora G, Jukema JW, Bax JJ, (2008). Relation of epicardial adipose tissue to coronary atherosclerosis. Am J Cardiol 102: 1602-1607.
37. Eid HM, Lyberg T, Arnesen H, Seljeflot I, (2007). Insulin and adiponectin inhibit the TNFalpha-induced ADMA accumulation in human endothelial cells: the role of DDAH. Atherosclerosis 194: e1-e8. (Pubitemid 47513102)
38. Fehmann HC, Heyn J, (2002). Plasma resistin levels in patients with type 1 and type 2 diabetes mellitus and in healthy controls. Horm Metab Res 34: 671-673. (Pubitemid 36398705)
39. Ferrannini E, Barrett EJ, Bevilacqua S, DeFronzo RA, (1983). Effect of fatty acids on glucose production and utilization in man. J Clin Invest 72: 1737-1747. (Pubitemid 14229053)
40. Ferri C, Desideri G, Valenti M, Bellini C, Pasin M, Santucci A, et al,. (1999). Early upregulation of endothelial adhesion molecules in obese hypertensive men. Hypertension 34: 568-573. (Pubitemid 29496435)
41. Galic S, Oakhill JS, Steinberg GR, (2010). Adipose tissue as an endocrine organ. Mol Cell Endocrinol 316: 129-139.
42. Gao YJ, Zeng ZH, Teoh K, Sharma AM, Abouzahr L, Cybulsky I, et al,. (2005). Perivascular adipose tissue modulates vascular function in the human internal thoracic artery. J Thorac Cardiovasc Surg 130: 1130-1136. (Pubitemid 41427351)
43. Gao YJ, Lu C, Su LY, Sharma AM, Lee RM, (2007). Modulation of vascular function by perivascular adipose tissue: the role of endothelium and hydrogen peroxide. Br J Pharmacol 151: 323-331. (Pubitemid 46842669)
44. Goran MI, Gower BA, (1998). Abdominal obesity and cardiovascular risk in children. Coron Artery Dis 9: 483-487. (Pubitemid 28517591)
45. Greenstein AS, Khavandi K, Withers SB, Sonoyama K, Clancy O, Jeziorska M, et al,. (2009). Local inflammation and hypoxia abolish the protective anticontractile properties of perivascular fat in obese patients. Circulation 119: 1661-1670.
46. Gronbaek M, (2002). Alcohol, type of alcohol, and all-cause and coronary heart disease mortality. Ann N Y Acad Sci 957: 16-20. (Pubitemid 34721650)
47. Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C, (2004). Definition of metabolic syndrome: report of the national heart, lung, and blood institute/American heart association conference on scientific issues related to definition. Circulation 109: 433-438. (Pubitemid 38133916)
48. de Haan CH, van Dielen FM, Houben AJ, de Leeuw PW, Huvers FC, De Mey JG, et al,. (1997). Peripheral blood flow and noradrenaline responsiveness: the effect of physiological hyperinsulinemia. Cardiovasc Res 34: 192-198. (Pubitemid 27261929)
49. Haslam DW, James WP, (2005). Obesity. Lancet 366: 1197-1209. (Pubitemid 41393598)
50. Home PD, Pocock SJ, Beck-Nielsen H, Curtis PS, Gomis R, Hanefeld M, et al,. (2009). Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 373: 2125-2135.
51. Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM, (1996). IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271: 665-668. (Pubitemid 26052915)
52. Hundal RS, Inzucchi SE, (2003). Metformin: new understandings, new uses. Drugs 63: 1879-1894. (Pubitemid 37108399)
53. Iantorno M, Chen H, Kim JA, Tesauro M, Lauro D, Cardillo C, et al,. (2007). Ghrelin has novel vascular actions that mimic PI 3-kinase-dependent actions of insulin to stimulate production of NO from endothelial cells. Am J Physiol Endocrinol Metab 292: E756-E764. (Pubitemid 46411053)
54. Jia SJ, Jiang DJ, Hu CP, Zhang XH, Deng HW, Li YJ, (2006). Lysophosphatidylcholine-induced elevation of asymmetric dimethylarginine level by the NADPH oxidase pathway in endothelial cells. Vascul Pharmacol 44: 143-148.
55. de Jongh RT, Serne EH, Ijzerman RG, de Vries G, Stehouwer CD, (2004). Free fatty acid levels modulate microvascular function: relevance for obesity-associated insulin resistance, hypertension, and microangiopathy. Diabetes 53: 2873-2882. (Pubitemid 39425913)
56. Kahn BB, Flier JS, (2000). Obesity and insulin resistance. J Clin Invest 106: 473-481. (Pubitemid 30666380)
57. Kim JA, Montagnani M, Koh KK, Quon MJ, (2006). Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation 113: 1888-1904. (Pubitemid 43739401)
58. Kissebah AH, Freedman DS, Peiris AN, (1989). Health risks of obesity. Med Clin North Am 73: 111-138. (Pubitemid 19032518)
59. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K, (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402: 656-660. (Pubitemid 129516334)
60. Korda M, Kubant R, Patton S, Malinski T, (2008). Leptin-induced endothelial dysfunction in obesity. Am J Physiol Heart Circ Physiol 295: H1514-H1521.
61. Laakso M, Edelman SV, Brechtel G, Baron AD, (1990). Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance. J Clin Invest 85: 1844-1852. (Pubitemid 20192958)
62. Lara-Castro C, Luo N, Wallace P, Klein RL, Garvey WT, (2006). Adiponectin multimeric complexes and the metabolic syndrome trait cluster. Diabetes 55: 249-259. (Pubitemid 43343322)
63. Lazar MA, (2007). Resistin- and Obesity-associated metabolic diseases. Horm Metab Res 39: 710-716. (Pubitemid 350099817)
64. Lee DE, Kehlenbrink S, Lee H, Hawkins M, Yudkin JS, (2009). Getting the message across: mechanisms of physiological cross talk by adipose tissue. Am J Physiol Endocrinol Metab 296: E1210-E1229.
65. van der Lely AJ, Tschop M, Heiman ML, Ghigo E, (2004). Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev 25: 426-457. (Pubitemid 38780667)
66. Levin ER, (1995). Endothelins. N Engl J Med 333: 356-363.
67. Lind L, Lithell H, (1993). Decreased peripheral blood flow in the pathogenesis of the metabolic syndrome comprising hypertension, hyperlipidemia, and hyperinsulinemia. Am Heart J 125: 1494-1497. (Pubitemid 23138405)
68. Martin SS, Qasim A, Reilly MP, (2008). Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J Am Coll Cardiol 52: 1201-1210.
69. Mather KJ, Mirzamohammadi B, Lteif A, Steinberg HO, Baron AD, (2002). Endothelin contributes to basal vascular tone and endothelial dysfunction in human obesity and type 2 diabetes. Diabetes 51: 3517-3523. (Pubitemid 35403459)
70. Mather KJ, Lteif A, Steinberg HO, Baron AD, (2004). Interactions between endothelin and nitric oxide in the regulation of vascular tone in obesity and diabetes. Diabetes 53: 2060-2066. (Pubitemid 38970755)
71. Matsubara M, Maruoka S, Katayose S, (2002). Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. Eur J Endocrinol 147: 173-180.
72. Mattagajasingh I, Kim CS, Naqvi A, Yamamori T, Hoffman TA, Jung SB, et al,. (2007). SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proc Natl Acad Sci U S A 104: 14855-14860. (Pubitemid 350003232)
73. Mavri A, Poredos P, Suran D, Gaborit B, Juhan-Vague I, Poredos P, (2011). Effect of diet-induced weight loss on endothelial dysfunction: early improvement after the first week of dieting. Heart Vessels 26: 31-38.
74. Mohamed F, Monge JC, Gordon A, Cernacek P, Blais D, Stewart DJ, (1995). Lack of role for nitric oxide (NO) in the selective destabilization of endothelial NO synthase mRNA by tumor necrosis factor-alpha. Arterioscler Thromb Vasc Biol 15: 52-57.
75. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, et al,. (2003). Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 289: 76-79. (Pubitemid 36026281)
76. Morrow VA, Foufelle F, Connell JM, Petrie JR, Gould GW, Salt IP, (2003). Direct activation of AMP-activated protein kinase stimulates nitric-oxide synthesis in human aortic endothelial cells. J Biol Chem 278: 31629-31639. (Pubitemid 37048341)
77. Motoshima H, Wu X, Mahadev K, Goldstein BJ, (2004). Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL. Biochem Biophys Res Commun 315: 264-271. (Pubitemid 38183103)
78. Muniyappa R, Iantorno M, Quon MJ, (2008). An integrated view of insulin resistance and endothelial dysfunction. Endocrinol Metab Clin North Am 37: 685-711. ix-x.
79. Nissen SE, Wolski K, (2007). Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 356: 2457-2471. (Pubitemid 46919772)
80. Nissen SE, Wolski K, (2010). Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med 170: 1911-1201.
81. Otani H, (2010). Oxidative stress as pathogenesis of cardiovascular risk associated with metabolic syndrome. Antioxid Redox Signal 15: 1911-1926.
82. Pasarica M, Sereda OR, Redman LM, Albarado DC, Hymel DT, Roan LE, et al,. (2009). Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes 58: 718-725.
83. Perticone F, Ceravolo R, Candigliota M, Ventura G, Iacopino S, Sinopoli F, et al,. (2001). Obesity and body fat distribution induce endothelial dysfunction by oxidative stress: protective effect of vitamin C. Diabetes 50: 159-165. (Pubitemid 32047995)
84. Piatti PM, Monti LD, Conti M, Baruffaldi L, Galli L, Phan CV, et al,. (1996). Hypertriglyceridemia and hyperinsulinemia are potent inducers of endothelin-1 release in humans. Diabetes 45: 316-321. (Pubitemid 26069045)
85. Pierce GL, Beske SD, Lawson BR, Southall KL, Benay FJ, Donato AJ, et al,. (2008). Weight loss alone improves conduit and resistance artery endothelial function in young and older overweight/obese adults. Hypertension 52: 72-79.
86. Pistrosch F, Passauer J, Fischer S, Fuecker K, Hanefeld M, Gross P, (2004). In type 2 diabetes, rosiglitazone therapy for insulin resistance ameliorates endothelial dysfunction independent of glucose control. Diabetes Care 27: 484-490. (Pubitemid 38174076)
87. Pittas AG, Joseph NA, Greenberg AS, (2004). Adipocytokines and insulin resistance. J Clin Endocrinol Metab 89: 447-452. (Pubitemid 38269842)
88. Rask-Madsen C, Dominguez H, Ihlemann N, Hermann T, Kober L, Torp-Pedersen C, (2003). Tumor necrosis factor-alpha inhibits insulin's stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans. Circulation 108: 1815-1821. (Pubitemid 37296090)
89. Reaven GM, Hoffman BB, (1987). A role for insulin in the aetiology and course of hypertension? Lancet 2: 435-437.
90. Rebuffe-Scrive M, Andersson B, Olbe L, Bjorntorp P, (1989). Metabolism of adipose tissue in intraabdominal depots of nonobese men and women. Metabolism 38: 453-458. (Pubitemid 19125880)
91. Rebuffe-Scrive M, Anderson B, Olbe L, Bjorntorp P, (1990). Metabolism of adipose tissue in intraabdominal depots in severely obese men and women. Metabolism 39: 1021-1025. (Pubitemid 20351258)
92. Ren J, (2004). Leptin and hyperleptinemia-from friend to foe for cardiovascular function. J Endocrinol 181: 1-10. (Pubitemid 38584659)
93. Saltiel AR, Kahn CR, (2001). Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414: 799-806. (Pubitemid 34000783)
94. Schinzari F, Tesauro M, Rovella V, Galli A, Mores N, Porzio O, et al,. (2010). Generalized impairment of vasodilator reactivity during hyperinsulinemia in patients with obesity-related metabolic syndrome. Am J Physiol Endocrinol Metab 299: E947-E952.
95. Schoonjans K, Auwerx J, (2000). Thiazolidinediones: an update. Lancet 355: 1008-1010. (Pubitemid 30148273)
96. Sekuri C, Tavli T, Avsar A, Sozcuer H, Uyanik BS, Ari Z, (2003). The acute effect of orlistat on endothelial function in young obese women. Int J Clin Pharmacol Res 23: 111-117. (Pubitemid 38821761)
97. Siekmeier R, Grammer T, Marz W, (2008). Roles of oxidants, nitric oxide, and asymmetric dimethylarginine in endothelial function. J Cardiovasc Pharmacol Ther 13: 279-297.
98. Sniderman AD, Cianflone K, (1995). Metabolic disruptions in the adipocyte-hepatocyte fatty acid axis as causes of HyperapoB. Int J Obes Relat Metab Disord 19 (Suppl. 1): S27-S33.
99. Soderberg S, Ahren B, Jansson JH, Johnson O, Hallmans G, Asplund K, et al,. (1999). Leptin is associated with increased risk of myocardial infarction. J Intern Med 246: 409-418. (Pubitemid 29479923)
100. Sola S, Mir MQ, Cheema FA, Khan-Merchant N, Menon RG, Parthasarathy S, et al,. (2005). Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study. Circulation 111: 343-348. (Pubitemid 40165342)
101. Soltis EE, Cassis LA, (1991). Influence of perivascular adipose tissue on rat aortic smooth muscle responsiveness. Clin Exp Hypertens A 13: 277-296.
102. Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD, (1996). Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest 97: 2601-2610.
103. Steinberg HO, Tarshoby M, Monestel R, Hook G, Cronin J, Johnson A, et al,. (1997). Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J Clin Invest 100: 1230-1239. (Pubitemid 27386309)
104. Sweeney G, (2010). Cardiovascular effects of leptin. Nat Rev Cardiol 7: 22-29.
105. Tack CJ, Lutterman JA, Vervoort G, Thien T, Smits P, (1996). Activation of the sodium-potassium pump contributes to insulin-induced vasodilation in humans. Hypertension 28: 426-432. (Pubitemid 26296046)
106. Tesauro M, Schinzari F, Iantorno M, Rizza S, Melina D, Lauro D, et al,. (2005). Ghrelin improves endothelial function in patients with metabolic syndrome. Circulation 112: 2986-2992. (Pubitemid 41612302)
107. Tesauro M, Schinzari F, Rovella V, Melina D, Mores N, Barini A, et al,. (2008). Tumor necrosis factor-alpha antagonism improves vasodilation during hyperinsulinemia in metabolic syndrome. Diabetes Care 31: 1439-1441.
108. Tesauro M, Schinzari F, Rovella V, Di Daniele N, Lauro D, Mores N, et al,. (2009). Ghrelin restores the endothelin 1/nitric oxide balance in patients with obesity-related metabolic syndrome. Hypertension 54: 995-1000.
109. Tesauro M, Schinzari F, Caramanti M, Lauro R, Cardillo C, (2010). Cardiovascular and metabolic effects of ghrelin. Curr Diab Rev 6: 228-235.
110. Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML, (2001). Circulating ghrelin levels are decreased in human obesity. Diabetes 50: 707-709. (Pubitemid 32242624)
111. UK Prospective Diabetes Study (UKPDS) Group (1998). Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352: 854-865.
112. Vague J, (1956). The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout, and uric calculous disease. Am J Clin Nutr 4: 20-34.
113. Van Guilder GP, Hoetzer GL, Dengel DR, Stauffer BL, DeSouza CA, (2006). Impaired endothelium-dependent vasodilation in normotensive and normoglycemic obese adult humans. J Cardiovasc Pharmacol 47: 310-313. (Pubitemid 44384071)
114. Vicent D, Ilany J, Kondo T, Naruse K, Fisher SJ, Kisanuki YY, et al,. (2003). The role of endothelial insulin signaling in the regulation of vascular tone and insulin resistance. J Clin Invest 111: 1373-1380. (Pubitemid 36554708)
115. Vitale C, Mercuro G, Cornoldi A, Fini M, Volterrani M, Rosano GM, (2005). Metformin improves endothelial function in patients with metabolic syndrome. J Intern Med 258: 250-256. (Pubitemid 41243057)
116. Wang CP, Hsu HL, Hung WC, Yu TH, Chen YH, Chiu CA, et al,. (2009a). Increased epicardial adipose tissue (EAT) volume in type 2 diabetes mellitus and association with metabolic syndrome and severity of coronary atherosclerosis. Clin Endocrinol (Oxf) 70: 876-882.
117. Wang S, Xu J, Song P, Viollet B, Zou MH, (2009b). In vivo activation of AMP-activated protein kinase attenuates diabetes-enhanced degradation of GTP cyclohydrolase I. Diabetes 58: 1893-1901.
118. Watanabe S, Tagawa T, Yamakawa K, Shimabukuro M, Ueda S, (2005). Inhibition of the renin-angiotensin system prevents free fatty acid-induced acute endothelial dysfunction in humans. Arterioscler Thromb Vasc Biol 25: 2376-2380. (Pubitemid 41552657)
119. Wellen KE, Hotamisligil GS, (2003). Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 112: 1785-1788. (Pubitemid 38063699)
120. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al,. (2001). Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86: 1930-1935. (Pubitemid 32472900)
121. Wong RH, Howe PR, Buckley JD, Coates AM, Kunz I, Berry NM, (2011). Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutr Metab Cardiovasc Dis (in press).
122. Woo KS, Chook P, Yu CW, Sung RY, Qiao M, Leung SS, et al,. (2004a). Effects of diet and exercise on obesity-related vascular dysfunction in children. Circulation 109: 1981-1986. (Pubitemid 38544488)
123. Woo KS, Chook P, Yu CW, Sung RY, Qiao M, Leung SS, et al,. (2004b). Overweight in children is associated with arterial endothelial dysfunction and intima-media thickening. Int J Obes Relat Metab Disord 28: 852-857. (Pubitemid 39005685)
124. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, et al,. (2002). Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8: 1288-1295. (Pubitemid 35373562)
125. Yki-Jarvinen H, (2004). Thiazolidinediones. N Engl J Med 351: 1106-1118.
126. Yki-Jarvinen H, Utriainen T, (1998). Insulin-induced vasodilatation: physiology or pharmacology? Diabetologia 41: 369-379. (Pubitemid 28157407)
127. Yoshizumi M, Perrella MA, Burnett JC Jr, Lee ME, (1993). Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half-life. Circ Res 73: 205-209. (Pubitemid 23173071)
128. Yudkin JS, Eringa E, Stehouwer CD, (2005). 'Vasocrine' signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease. Lancet 365: 1817-1820. (Pubitemid 40744663)
129. Zeng G, Nystrom FH, Ravichandran LV, Cong LN, Kirby M, Mostowski H, et al,. (2000). Roles for insulin receptor, PI3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells. Circulation 101: 1539-1545. (Pubitemid 30180890)
130. Zhang L, Vincent MA, Richards SM, Clerk LH, Rattigan S, Clark MG, et al,. (2004). Insulin sensitivity of muscle capillary recruitment in vivo. Diabetes 53: 447-453. (Pubitemid 38174562)
131. Ziccardi P, Nappo F, Giugliano G, Esposito K, Marfella R, Cioffi M, et al,. (2002). Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation 105: 804-809. (Pubitemid 34174919)