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...

BackgroundRisk factors in childhood create a life-long burden important in the development of cardiovascular (CV) disease in adulthood. Many risk factors for CV disease (e.g., hypertension) also increase the risk of renal disease. However, the importance of childhood risk factors on the development of chronic kidney disease and end-stage renal disease (ESRD) is not well characterized.MethodsThe current observations include data from Bogalusa Heart Study participants who were examined multiple times as children between 1973 and 1988.ResultsThrough 2006, fifteen study participants subsequently developed ESRD in adulthood; seven with no known overt cause. Although the Bogalusa Heart Study population is 63% white and 37% black and 51% male and 49% female, all seven ESRD cases with no known overt cause were black males (p < 0.001). Mean age-adjusted systolic and diastolic blood pressure in childhood was higher among the ESRD cases (114.5 mmHg and 70.1 mmHg, respectively) compared to black (103.0 mmHg and 62.3 mmHg, respectively) and white (mean = 103.3 mmHg and 62.3 mmHg, respectively) boys who didn't develop ESRD. The mean age-adjusted body mass index in childhood was 23.5 kg/m2 among ESRD cases and 18.6 kg/m2 and 18.9 kg/m2 among black and white boys who didn't develop ESRD, respectively. Plasma glucose in childhood was not significantly associated with ESRD.ConclusionThese data suggest black males have an increased risk of ESRD in young adulthood. Elevated body mass index and blood pressure in childhood may increase the risk for developing ESRD as young adults.

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Metabolic syndrome increases the risk of developing diabetes as well as cardiovascular and kidney diseases. This research studied the effects of tesaglitazar, a dual-acting peroxisome proliferator-activated receptor (PPAR)α/γ agonist, on metabolic abnormalities and kidney injury in obese Zucker rats (OZR). Lean Zucker rats (LZR) and OZR were used as control groups. Tesaglitazar (1 µmol/kg/day) was given for 8 weeks in the treatment group (OZR-T). Metabolic parameters, 24-hour urine albumin excretion, and tail blood pressure were measured. Glomerular filtration rate by inulin clearance, abdominal fat and renal histology were determined at the end of the study. In comparison with the OZR and OZR-T groups, the LZR control animals’ parameters were significantly more favorable in all measures. Tesaglitazar treatment in OZR significantly reduced nonfasting glucose, C-reactive protein levels and improved dyslipidemia. Body weight, blood pressure and urine albumin excretion were lower, but the adjusted glomerular filtration rate higher, in the OZR-T group than in the OZR controls. Glomerular area, mesangial expansion and tubulointerstitial changes were ameliorated, and the glomerular expression of desmin was markedly more decreased in the OZR-T group than in the OZR controls. Therefore, the PPARα/γ agonist tesaglitazar significantly improved metabolic abnormalities and renal function, decreased blood pressure, and protected against glomerular and interstitial damage in OZR.