Leptin and the central neural mechanisms of obesity hypertension

Abstract

The prevalence of obesity is rising at an alarming rate worldwide, with consequent increases in type 2 diabetes, hypertension and cardiovascular morbidity and mortality. Central neural mechanisms, via the activation of the sympathetic nervous system may contribute to obesity-related cardiovascular diseases through the promotion of hypertension, dysrhythmia and atherosclerosis. However, the mechanisms responsible for this sympatho activation have not been identified. Leptin is an adipocyte-derived hormone that promotes weight loss by reducing appetite and by increasing energy expenditure through sympathetic stimulation to thermogenic tissue. Leptin also produces sympathoactivation to kidneys, hindlimb and adrenal glands, suggesting that the obesity-associated increase in sympathetic nerve activity could be due in part to these sympathetic effects of leptin. However, most human obesity appears to be associated with leptin resistance. Recent studies indicate that leptin resistance may be selective, with preservation of adverse sympathetic effects despite the loss of the metabolic actions of leptin. The leptin receptor is expressed in several hypothalamic nuclei including the arcuate nucleus. The melanocortin system, neuropeptide Y and corticotrophin-releasing factor have emerged as principal neuropeptide mediators of leptin action in the arcuate nucleus. These neuropeptides exert varying effects by different pathways. Several other candidate hypothalamic pathways that can mediate the effects of leptin have been identified. The understanding of neuronal signaling pathways involved in leptin signaling and energy balance has opened new research possibilities for the treatment of obesity.