Leptin and hypertension in obesity

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 IntroductionObesity 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 antiLeptin and hypertension in obesity 164Bravo et al obesity hormone, base...

Association between adipocytokines and insulin resistance in Indian hypertensive patients

“…14 Leptin has several effects such as stimulation of the RAS and sympathetic nervous system which may affect BP levels in humans. 12,13,31 Moreover, in multiple logistic regression analysis leptin is an important predictor of HT in our population suggesting that leptin may be playing an important role in the development of HT in our population. Taken together, leptin does indeed have peripheral physiological effects that suggest it may be a link in the triad of obesity, IR, and HT.…”

“…Although data from available animal studies clearly indicate an association between leptin and HT, results of human studies have been less definitive. [9][10][11][12][13][14][15] Though several studies have shown that adiponectin correlates negatively with BP, the results of studies on the relation between adiponectin and HT have been inconsistent. 7,8,16,17 Resistin, a novel cysteine-rich protein secreted by adipocytes, has been proposed to serve as a link between obesity and IR in rodents, but this has remained controversial.…”

Physiological potential of cytokines and liver damages

“…Elevation of the inflammatory markers above normal levels is an independent predictor of several chronic diseases, including coronary heart disease, stroke, diabetes, atherosclerosis and insulin resistance. [41] Cytokines and hepatic cholestasis Cholestasis is defined as a decrease in canalicular bile flow that results in accumulation of bile in hepatocytes and canaliculi. [42] Hepatocellular cholestasis may be due to functional or structural alterations in the biliary tree.…”

Analysis of Heart Period and Arterial Pressure Variability in Childhood Hypertension

“…16 Autonomic dysregulation is also observed in adult obesity, 17 particularly if accompanied by hypertension. 18 The aim of this study was to assess whether noninvasive analysis of the RR interval and arterial blood pressure variability in time and frequency domains could detect early autonomic alterations in children with arterial pressure values in the highest percentile range, as compared with a control population of similar age.…”