R E V I E W Leptin and hyper tension in obesity Paco E Bravo1 Stephen Morse1 David M Borne2 Erwin A Aguilar1 Efrain Reisin1 1Sections of Nephrology and 2Comprehensive Medicine, Department of Internal Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA Correspondence: Efrain Reisin Chief of the Section of Nephrology, Department of Internal Medicine, Louisiana State University Health Sciences Center 1542 Tulane Avenue, New Orleans, LA 70112, USA Tel +1 504 568 8655 Fax +1 504 454 8218 Email ereisi@lsuhsc.edu Abstract: Leptin, a peptide discovered more than 10 years ago, decreases food intake and increases sympathetic nerve activity to both thermogenic and nonthermogenic tissue. Leptin was initially believed to be an anti-obesity hormone, owing to its metabolic effects. However, obese individuals, for unknown reasons, become resistant to the satiety and weight-reducing effect of the hormone, but preserve leptin-mediated sympathetic activation to nonthermogenic tissue such as kidney, heart, and adrenal glands. Leptin has been shown to influence nitric oxide production and natriuresis, and along with chronic sympathetic activation, especially to the kidney, it may lead to sodium retention, systemic vasoconstriction, and blood pressure elevation. Consequently, leptin is currently considered to play an important role in the development of hypertension in obesity. Keywords: leptin, renal sympathetic nerve activity, blood pressure, obesity, selective leptin resistance, nitric oxide, natriuresis Introduction Obesity is considered a world health problem especially in western industrialized countries, where its incidence and prevalence are rising steadily, along with several comorbities associated with it, such as hypertension, diabetes, dyslipidemia, atherosclerosis, and chronic renal failure. Among these, hypertension – a very important cardiovascular risk factor – has been observed in roughly 50% of obese individuals, which has led researchers to consider obesity as one of the most common causes of hypertension. Hence, hypertension in obesity has become a topic of extensive ongoing research. Now, several mechanisms have been implicated in the association between obesity and hypertension, including activation of sympathetic nervous system, abnormal renal sodium handling, insulin resistance, and physical compression of the kidney (Haynes et al 1998). In this respect, sympathetic activation appears to mediate at least part of the obesity-induced hypertension, and leptin, the adipocyte-derived hormone, has recently been postulated as one of the possible causes of this sympathetic activation in obesity. Leptin is a 167 amino acid hormone discovered in 1994 that is almost exclusively produced by adipose tissue and possibly secreted by a constitutive mechanism. The effects of this peptide are mediated by receptors (Ob-R), most of them located in the hypothalamus, belonging to the class l cytokine receptor family. As of yet, 6 leptin receptor isoforms are known (Ahima and Flier 2000). Leptin is considered a homeostatic hormone regulating food intake and body weight. Acting on the hypothalamic nuclei, leptin decreases appetite, and increases energy expenditure through sympathetic activation, which consequently decreases adipose tissue mass and body weight. The hormone levels are decreased during fasting and increased after several days of overfeeding as an effort to help regulate energy balance in humans. Due to latter homeostatic control mechanism, leptin is an anti- Vascular Health and Risk Management 2006:2(2) 163–169 © 2006 Dove Medical Press Ltd. All rights reserved 163