Leptin Signaling in Blood Platelets as a Target for Therapeutic Intervention

Jerzy      Beltowski

Abstract

Leptin is a peptide hormone secreted by adipose tissue which is primarily involved in the regulation of food intake and energy expenditure. Apart from the brain, leptin receptors are expressed in many peripheral tissues. Plasma leptin concentration is markedly increased in most patients with obesity/metabolic syndrome reflecting greater amount of adipose tissue and resistance to anorectic effect of this hormone. Recent studies indicate that leptin receptors are also expressed in blood platelets and that leptin stimulates platelet aggregation at least in some experimental conditions. In addition, thrombus formation is impaired in leptin deficient ob/ob mice and leptin supplementation corrects these abnormalities. Clinical studies suggest the link between hyperleptinemia and atherothrombosis independently of body weight. These data indicate that leptin signaling in platelets may be involved in enhanced tendency to thrombosis and atherosclerosis in patients with the metabolic syndrome. In this article I characterize the effect of leptin on platelet function as well as possible therapeutic interventions aimed to target leptin signaling in platelets.

Keywords: Leptin, obesity, platelets, thrombosis, atherosclerosis, antiplatelet drugs, Metabolic syndrome, hypertriglyceridemia, hyperuricemia, venous thrombosis, fibrinogen, hyperlipoproteinemia, adipokines, adiponectin, resistin, visfatin, mitogen-activated protein kinases (MAPK), phoinositide 3-kinase, protein kinase C, P-selectin, throm-bospondin-1, RANTES, CD40 ligand, PLC, PLA2, PKC, Jak2 inhibitor, AG-490, PI3K, LY294002, ERK, PDE3A, TxA2 formation