CARDIOVASCULAR CONSEQUENCES OF OBESITY - ROLE OF LEPTIN

1. Several mechanisms have been implicated in the association between obesity and hypertension, including salt-sensitivity, insulin resistan ce and sympathetic activation. Obese animals and humans exhibit exagge rated blood pressure responses to increases in salt intake. 2. Althoug h insulin resistance is common in obesity, it is clear that abnormal i nsulin action is not the sole or sufficient cause of hypertension in o besity. Obesity is associated with increased activity of the sympathet ic nervous system. Sympathetic blockade has been reported to attenuate sodium retention and hypertension in experimental models of obesity. 3. The mediators responsible for salt sensitivity, insulin resistance and sympathetic activation in obesity remain unclear. 4. The novel pro tein hormone leptin is produced almost exclusively by adipose tissue a nd acts in the central nervous system through a specific receptor and multiple neuropeptide pathways to decrease appetite and increase energ y expenditure. 5. Increasing evidence suggests that leptin may have wi der actions influencing autonomic, cardiovascular, renal and endocrine function. We have shown that leptin increases sympathetic nerve activ ity to kidney, hindlimb and adrenal gland, in addition to brown adipos e tissue. 6. Despite this sympathoexcitatory action, acute systemic ad ministration of leptin does not acutely increase arterial pressure or heart rate in anaesthetized animals. This may reflect opposing antihyp ertensive actions of leptin. For example, leptin increases renal sodiu m and water excretion, apparently through a direct tubular action. In addition, leptin increases systemic insulin sensitivity, even in the a bsence of weight loss. 7. In conclusion, leptin may act as a mediator linking body adiposity with changes in insulin action, sympathetic neu ral out-flow and renal sodium excretion. Alterations in leptin generat ion or action may, in part, underlie the sympathetic, endocrine and re nal consequences of obesity.