Inverse Association of Serum Leptin with Flow-Mediated Dilatation Independent of Body Fat Distribution, Insulin Resistance, Oxidative Stress and Inflammation in Young Women
DOI:
https://doi.org/10.12970/2310-9971.2014.02.01.4Keywords:
Endothelial function, leptin, trunk/leg fat ratio, hsCRP, serum ALT.Abstract
Chronic hyperleptinemia found in obesity has been shown to be associated with endothelial dysfunction, an early and fundamental event in the development of atherosclerosis. We examined whether elevated leptin levels are associated with decreased endothelial function in young women. Flow-mediated dilatation (FMD) in the brachial artery, fat mass by dual-energy absorptiometry, Matsuda index, an insulin sensitivity index derived from an oral glucose tolerance test, serum leptin, adiponectin, hepatic enzymes, lipid profile, high-sensitivity C-reactive protein (hsCRP) and urinary 8-epi-prostaglandin F-2α (8-epi-PGF2α), a marker of oxidative stress, were measured in 44 young women. After adjustment for age, FMD was associated inversely with percentage of body fat, trunk fat and leg fat. In addition, FMD showed inverse associations with serum leptin, log hsCRP and log alanine aminotransferase (all p<0.05 or less). In multiple regression analysis only leptin emerged as an independent determinant of FMD (standardized beta、-0.325) and explained 11% of FMD variability. In conclusion, leptin serum levels had an impact on arterial distensibility in young women, a finding that raises the possibility that leptin levels in the general population during early adulthood may already be relevant to the development of vascular dysfunction.References
[1] Must A, Jacques PF, Dallal GE, Bajema CJ, Dietz WH. Longterm morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935. N Engl J Med 1992; 327: 1350-5. http://dx.doi.org/10.1056/NEJM199211053271904
[2] Fernhall B, Agiovlasitis S. Arterial function in youth: window into cardiovascular risk. J Appl Physiol 2008; 105: 325-33. http://dx.doi.org/10.1152/japplphysiol.00001.2008
[3] Bots ML, Hoes AW, Hofman A, Witteman JC, Grobbee DE. Cross-sectionally assessed carotid intima-media thickness relates to long-term risk of stroke, coronary heart disease and death as estimated by available risk functions. J Intern Med 1999; 245: 269-76. http://dx.doi.org/10.1046/j.1365-2796.1999.0442f.x
[4] Green DJ, Jones H, Thijssen D, Cable NT, Atkinson G. Flowmediated dilation and cardiovascular event prediction: does nitric oxide matter? Hypertension 2011; 57: 363-9. http://dx.doi.org/10.1161/HYPERTENSIONAHA.110.167015
[5] Tounian P, Aggoun Y, Dubern B, et al. Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study. Lancet 2001; 358: 1400-4. http://dx.doi.org/10.1016/S0140-6736(01)06525-4
[6] Woo KS, Chook P, Yu CW, et al. Overweight in children is associated with arterial endothelial dysfunction and intimamedia thickening. Int J Obes 2004; 28: 852-7. http://dx.doi.org/10.1038/sj.ijo.0802539
[7] Zhu W, Huang X, He J, Li M, Neubauer H. Arterial intimamedia thickening and endothelial dysfunction in obese Chinese children. Eur J Pediatr 2005; 164: 337-44. http://dx.doi.org/10.1007/s00431-005-1642-y
[8] Singhal A. Endothelial dysfunction: role in obesity-related disorders and the early origins of CVD. Proc Nutr Soc 2005; 64: 15-22. http://dx.doi.org/10.1079/PNS2004404
[9] Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-9. http://dx.doi.org/10.1007/BF00280883
[10] Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999; 22: 1462-70. http://dx.doi.org/10.2337/diacare.22.9.1462
[11] Friedwald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502.
[12] Wu B, Fukuo K, Suzuki K, Yoshino G, Kazumi T. Relationships of systmic oxdative stress to body fat distribution, adipokines and inflammatory makers in healthy middle-aged women. Endrocr J 2009; 56: 779-82. http://dx.doi.org/10.1507/endocrj.K08E-332
[13] Roberts LJ 2nd, Morrow JD. The generation and actions of isoprostanes. Biochim Biophys Acta 1997; 1345: 21-135.
[14] Corretti MC, Anderson TJ, Benjamin EJ, et al. International Brachial Artery Reactivity Task Force: Guidelines for the ultrasound assessment of endothelial-dependent flowmediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002; 39: 257-65. http://dx.doi.org/10.1016/S0735-1097(01)01746-6
[15] Tomiyama H, Matsumoto C, Yamada J, et al. The relationships of cardiovascular disease risk factors to flowmediated dilatation in Japanese subjects free of cardiovascular disease. Hypertens Res 2008; 31: 2019-25. http://dx.doi.org/10.1291/hypres.31.2019
[16] Ho SC, Wu S, Chan SG, Sham A. Menopausal transition and changes of body composition: a prospective study in Chinese perimenopausal women. Int J Obes (Lond) 2010; 34: 1265- 74. http://dx.doi.org/10.1038/ijo.2010.33
[17] Whincup PH, Gilg JA, Donald AE, et al. Arterial distensibility in adolescents: the influence of adiposity, the metabolic syndrome, and classic risk factors. Circulation 2005; 112: 1789-97. http://dx.doi.org/10.1161/CIRCULATIONAHA.104.532663
[18] Peña AS, Wiltshire E, MacKenzie K, et al. Vascular endothelial and smooth muscle function relates to body mass index and glucose in obese and non-obese children. J Clin Endocrinol Metab 2006; 91: 4467-71. http://dx.doi.org/10.1210/jc.2006-0863
[19] Singhal A, Farooqi IS, Cole TJ, et al. Influence of leptin on arterial distensibility: a novel link between obesity and cardiovascular disease? Circulation 2002; 106: 1919-24. http://dx.doi.org/10.1161/01.CIR.0000033219.24717.52
[20] Knudson JD, Payne GA, Borbouse L, Tune JD. Leptin and mechanisms of endothelial dysfunction and cardiovascular disease. Curr Hypertens Rep 2008; 10: 434-9. http://dx.doi.org/10.1007/s11906-008-0082-2
[21] Patel SB, Reams GP, Spear RM, Freeman RH, Villarreal D. Leptin: linking obesity, the metabolic syndrome, and cardiovascular disease. Curr Hypertens Rep 2008; 10: 131- 7. http://dx.doi.org/10.1007/s11906-008-0025-y
[22] Korda M, Kubant R, Patton S, Malinski T. Leptin-induced endothelial dysfunction in obesity. Am J Physiol Heart Circ Physiol 2008; 295: H1514-21. http://dx.doi.org/10.1152/ajpheart.00479.2008
[23] Knudson JD, Dincer UD, Zhang C, et al. Leptin receptors are expressed in coronary arteries and hyperleptinemia causes significant coronary endothelial dysfunction. Am J Physiol Heart Circ Physiol 2005; 289: H48-56. http://dx.doi.org/10.1152/ajpheart.01159.2004
[24] Wang J, Wang H, Luo W, et al. Leptin-induced endothelial dysfunction is mediated by sympathetic nervous system activity. J Am Heart Assoc 2013; 16; 2: e000299.
[25] Manuel-Apolinar L1, López-Romero R, Zarate A, et al. Leptin mediated ObRb receptor increases expression of adhesion intercellular molecules and cyclooxygenase 2 on murine aorta tissue inducing endothelial dysfunction. Int J Clin Exp Med 2013; 6: 192-6.
[26] Be towski J. Leptin and the regulation of endothelial function in physiological and pathological conditions. Clin Exp Pharmacol Physiol 2012; 39: 168-78. http://dx.doi.org/10.1111/j.1440-1681.2011.05623.x
[27] Tanaka M, Yoshida T, Wu B, Fukuo K, Kazumi T. FTO, abdominal adiposity, fasting hyperglycemia associated with elevated HbA1c in Japanese middle-aged women. J Athero Thromb 2012; 19: 633-42. http://dx.doi.org/10.5551/jat.11940