Year: 2004
Type: review
Abstract: Obesity is associated with increased cardiovascular morbidity and mortality, in part through development of hypertension. Recent observations suggest that the cardiovascular actions of leptin may help explain the link between excess fat mass and cardiovascular diseases. Leptin is an adipocyte-derived hormone that acts in the central nervous system to promote weight loss by decreasing food intake and increasing metabolic rate. Leptin causes a significant increase in overall sympathetic nervous activity, which appears to be due to direct hypothalamic effects and is mediated by neuropeptide systems such as the melanocortin system and corticotropin-releasing hormone. Renal sympathoactivation to leptin is preserved in the presence of obesity, despite resistance to the metabolic effects of leptin. Such selective leptin resistance, in the context of circulating hyperleptinemia, could predispose to obesity-related hypertension. Some in vitro studies have suggested that leptin may have peripheral actions such as endothelium-mediated vasodilation that might oppose sympathetically induced vasoconstriction. However, we and others have shown that leptin does not have direct vasodilator effects in vivo. The fact that chronic leptin administration or overexpression of leptin produces hypertension supports the concept that the hemodynamic actions of leptin are due predominantly to sympathetic activation. Exploration of the sites and mechanisms of leptin resistance should provide novel therapeutic strategies for obesity, insulin resistance, and hypertension.
DOI: 10.1210/rp.59.1.225
Author: K. Rahmouni
Institution: University of Iowa
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W2017356413