Circulation. 2002;105:804-809
Published online before print January 14, 2002, doi: 10.1161/hc0702.104279
Published online before print January 14, 2002, doi: 10.1161/hc0702.104279
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(Circulation. 2002;105:804.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Reduction of Inflammatory Cytokine Concentrations and Improvement of Endothelial Functions in Obese Women After Weight Loss Over One Year
From the Department of Geriatrics and Metabolic Diseases, Chair of Metabolic Diseases (P.Z., F.N., R.M., D.G.), Chair of Plastic Surgery (G.G., F.D.), and the Department of General Pathology, Chair of Clinical Pathology (K.E., M.C., A.M.M.), Second University of Naples, Italy.
Correspondence to Dario Giugliano, MD, Dept of Geriatrics and Metabolic Diseases, Policlinico della Seconda Università di Napoli, Piazza Miraglia, 80138 Napoli, Italy. E-mail dario.giugliano{at}unina2.it
Background— Visceral fat is a key regulator site for the process of inflammation, and atherosclerotic lesions are essentially an inflammatory response.
Methods and Results— Fifty-six healthy premenopausal obese women (age range 25 to 44 years, body mass index 37.2±2.2, waist to hip ratio range 0.78 to 0.92) and 40 age-matched normal weight women were studied. Compared with nonobese women, obese women had increased basal concentrations of tumor necrosis factor-
(TNF-, P<0.01), interleukin-6 (IL-6, P<0.01), P-selectin (P<0.01), intercellular adhesion molecule-1 (ICAM-1, P<0.02), and vascular adhesion molecule-1 (VCAM-1, P<0.05). Vascular responses to L-arginine (3 g IV), the natural precursor of nitric oxide, were impaired in obese women: reductions in mean blood pressure (P<0.02), platelet aggregation to adenosine diphosphate (P<0.05), and blood viscosity (P<0.05) were significantly lower as compared with those in the nonobese group. Concentrations of TNF- and IL-6 were related (P<0.01) to visceral obesity, as well as to adhesin levels and responses to L-arginine. After 1 year of a multidisciplinary program of weight reduction (diet, exercise, behavioral counseling), all obese women lost at least 10% of their original weight (9.8±1.5 kg, range 7.5 to 13 kg). Compared with baseline, sustained weight loss was associated with reduction of cytokine (P<0.01) and adhesin (P<0.02) concentrations and with improvement of vascular responses to L-arginine.
Conclusion— In obese women, endothelial activation correlates with visceral body fat, possibly through inappropriate secretion of cytokines. Weight loss represents a safe method for downregulating the inflammatory state and ameliorating endothelial dysfunction in obese women.
Key Words: obesity • weight loss • cell adhesion molecules • interleukins • endothelium
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S. Klein, N. F. Sheard, X. Pi-Sunyer, A. Daly, J. Wylie-Rosett, K. Kulkarni, and N. G. Clark Weight Management Through Lifestyle Modification for the Prevention and Management of Type 2 Diabetes: Rationale and Strategies: A statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition Diabetes Care, August 1, 2004; 27(8): 2067 - 2073. [Full Text] [PDF]
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J. F. Keaney Jr, J. M. Massaro, M. G. Larson, R. S. Vasan, P. W. F. Wilson, I. Lipinska, D. Corey, P. Sutherland, J. A. Vita, and E. J. Benjamin Heritability and correlates of intercellular adhesion molecule-1 in the Framingham Offspring Study J. Am. Coll. Cardiol., July 7, 2004; 44(1): 168 - 173. [Abstract] [Full Text] [PDF]
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A. S. Ryan and B. J. Nicklas Reductions in Plasma Cytokine Levels With Weight Loss Improve Insulin Sensitivity in Overweight and Obese Postmenopausal Women Diabetes Care, July 1, 2004; 27(7): 1699 - 1705. [Abstract] [Full Text] [PDF]
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T. Skurk, V. van Harmelen, and H. Hauner Angiotensin II Stimulates the Release of Interleukin-6 and Interleukin-8 From Cultured Human Adipocytes by Activation of NF-{kappa}B Arterioscler Thromb Vasc Biol, July 1, 2004; 24(7): 1199 - 1203. [Abstract] [Full Text] [PDF]
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K. Esposito, F. Giugliano, C. Di Palo, G. Giugliano, R. Marfella, F. D'Andrea, M. D'Armiento, and D. Giugliano Effect of Lifestyle Changes on Erectile Dysfunction in Obese Men: A Randomized Controlled Trial JAMA, June 23, 2004; 291(24): 2978 - 2984. [Abstract] [Full Text] [PDF]
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C. S. Saigal Obesity and Erectile Dysfunction: Common Problems, Common Solution? JAMA, June 23, 2004; 291(24): 3011 - 3012. [Full Text] [PDF]
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S. Klein, L. Fontana, V. L. Young, A. R. Coggan, C. Kilo, B. W. Patterson, and B. S. Mohammed Absence of an Effect of Liposuction on Insulin Action and Risk Factors for Coronary Heart Disease N. Engl. J. Med., June 17, 2004; 350(25): 2549 - 2557. [Abstract] [Full Text] [PDF]
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S. T. Weiss and S. Shore Obesity and Asthma: Directions for Research Am. J. Respir. Crit. Care Med., April 15, 2004; 169(8): 963 - 968. [Full Text] [PDF]
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B. J Nicklas, W. Ambrosius, S. P Messier, G. D Miller, B. W. Penninx, R. F Loeser, S. Palla, E. Bleecker, and M. Pahor Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial Am. J. Clinical Nutrition, April 1, 2004; 79(4): 544 - 551. [Abstract] [Full Text] [PDF]
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C. J. Hukshorn, J. H. N. Lindeman, K. H. Toet, W. H. M. Saris, P. H. C. Eilers, M. S. Westerterp-Plantenga, and T. Kooistra Leptin and the Proinflammatory State Associated with Human Obesity J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1773 - 1778. [Abstract] [Full Text] [PDF]
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E. J. Benjamin, M. G. Larson, M. J. Keyes, G. F. Mitchell, R. S. Vasan, J. F. Keaney Jr, B. T. Lehman, S. Fan, E. Osypiuk, and J. A. Vita Clinical Correlates and Heritability of Flow-Mediated Dilation in the Community: The Framingham Heart Study Circulation, February 10, 2004; 109(5): 613 - 619. [Abstract] [Full Text] [PDF]
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W. A. Hsueh and D. Bruemmer Peroxisome Proliferator-Activated Receptor {gamma}: Implications for Cardiovascular Disease Hypertension, February 1, 2004; 43(2): 297 - 305. [Abstract] [Full Text] [PDF]
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M. Pynn, K. Schafer, S. Konstantinides, and M. Halle Exercise Training Reduces Neointimal Growth and Stabilizes Vascular Lesions Developing After Injury in Apolipoprotein E-Deficient Mice Circulation, January 27, 2004; 109(3): 386 - 392. [Abstract] [Full Text] [PDF]
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M. Wolf, J. Sauk, A. Shah, K. Vossen Smirnakis, R. Jimenez-Kimble, J. L. Ecker, and R. Thadhani Inflammation and Glucose Intolerance: A prospective study of gestational diabetes mellitus Diabetes Care, January 1, 2004; 27(1): 21 - 27. [Abstract] [Full Text] [PDF]
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R. Marfella, K. Esposito, M. Siniscalchi, F. Cacciapuoti, F. Giugliano, D. Labriola, M. Ciotola, C. Di Palo, L. Misso, and D. Giugliano Effect of Weight Loss on Cardiac Synchronization and Proinflammatory Cytokines in Premenopausal Obese Women Diabetes Care, January 1, 2004; 27(1): 47 - 52. [Abstract] [Full Text] [PDF]
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M. Raitakari, T. Ilvonen, M. Ahotupa, T. Lehtimaki, A. Harmoinen, P. Suominen, J. Elo, J. Hartiala, and O. T. Raitakari Weight Reduction With Very-Low-Caloric Diet and Endothelial Function in Overweight Adults: Role of Plasma Glucose Arterioscler Thromb Vasc Biol, January 1, 2004; 24(1): 124 - 128. [Abstract] [Full Text] [PDF]
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J. S. Sidhu, D. Cowan, and J.-C. Kaski The effects of rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, on markers of endothelial cell activation, C-reactive protein, and fibrinogen levels in non-diabetic coronary artery disease patients J. Am. Coll. Cardiol., November 19, 2003; 42(10): 1757 - 1763. [Abstract] [Full Text] [PDF]
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M. E. Widlansky, N. Gokce, J. F. Keaney Jr, and J. A. Vita The clinical implications of endothelial dysfunction J. Am. Coll. Cardiol., October 1, 2003; 42(7): 1149 - 1160. [Abstract] [Full Text] [PDF]
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V. Palmieri, R. P. Tracy, M. J. Roman, J. E. Liu, L. G. Best, J. N. Bella, D. C. Robbins, B. V. Howard, and R. B. Devereux Relation of Left Ventricular Hypertrophy to Inflammation and Albuminuria in Adults With Type 2 Diabetes: The Strong Heart Study Diabetes Care, October 1, 2003; 26(10): 2764 - 2769. [Abstract] [Full Text] [PDF]
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K. Esposito, C. Di Palo, R. Marfella, and D. Giugliano The Effect of Weight Loss on Endothelial Functions in Obesity: Response to Sciacqua et al. Diabetes Care, October 1, 2003; 26(10): 2968 - 2969. [Full Text] [PDF]
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 M. Swaminathan, B. G. Phillips-Bute, P. J. Conlon, P. K. Smith, M. F. Newman, and M. Stafford-Smith The association of lowest hematocrit during cardiopulmonary bypass with acute renal injury after coronary artery bypass surgery Ann. Thorac. Surg., September 1, 2003; 76(3): 784 - 791. [Abstract] [Full Text] [PDF]
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M. Tomaszewski, F. J. Charchar, M. Przybycin, L. Crawford, A. M. Wallace, K. Gosek, G. D. Lowe, E. Zukowska-Szczechowska, W. Grzeszczak, N. Sattar, et al. Strikingly Low Circulating CRP Concentrations in Ultramarathon Runners Independent of Markers of Adiposity: How Low Can You Go? Arterioscler Thromb Vasc Biol, September 1, 2003; 23(9): 1640 - 1644. [Abstract] [Full Text] [PDF]
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 T. B. Ledue and N. Rifai Preanalytic and Analytic Sources of Variations in C-reactive Protein Measurement: Implications for Cardiovascular Disease Risk Assessment Clin. Chem., August 1, 2003; 49(8): 1258 - 1271. [Abstract] [Full Text] [PDF]
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G. F. Elphick, J. Wieseler-Frank, B. N. Greenwood, J. Campisi, and M. Fleshner B-1 cell (CD5+/CD11b+) numbers and nIgM levels are elevated in physically active vs. sedentary rats J Appl Physiol, July 1, 2003; 95(1): 199 - 206. [Abstract] [Full Text] [PDF]
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O. Hamdy, S. Ledbury, C. Mullooly, C. Jarema, S. Porter, K. Ovalle, A. Moussa, A. Caselli, A. E. Caballero, P. A. Economides, et al. Lifestyle Modification Improves Endothelial Function in Obese Subjects With the Insulin Resistance Syndrome Diabetes Care, July 1, 2003; 26(7): 2119 - 2125. [Abstract] [Full Text] [PDF]
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N. Sattar, J. Ramsay, L. Crawford, H. Cheyne, and I. A. Greer Classic and Novel Risk Factor Parameters in Women With a History of Preeclampsia Hypertension, July 1, 2003; 42(1): 39 - 42. [Abstract] [Full Text] [PDF]
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R. C. Christian, D. A. Dumesic, T. Behrenbeck, A. L. Oberg, P. F. Sheedy II, and L. A. Fitzpatrick Prevalence and Predictors of Coronary Artery Calcification in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2562 - 2568. [Abstract] [Full Text] [PDF]
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 C. J. Lyon, R. E. Law, and W. A. Hsueh Minireview: Adiposity, Inflammation, and Atherogenesis Endocrinology, June 1, 2003; 144(6): 2195 - 2200. [Abstract] [Full Text] [PDF]
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