Adiponectin as a therapeutic target for obesity-related metabolic and cardiovascular disorders

Abstract

Obesity is the major risk factor for the metabolic syndrome, which encompasses a cluster of inter-related metabolic risk factors for type 2 diabetes mellitus (T2DM), atherosclerosis, and cardiovascular diseases. Adiponectin, a major adipokine secreted from adipocytes, plays an important role in obesity-related metabolic and cardiovascular diseases. Longitudinal studies from different ethnic groups have identified low levels of plasma adiponectin (hypoadiponectinemia) to be an independent risk factor for T2DM, hypertension, and coronary artery diseases. On the other hand, results from various animal models have demonstrated the role of adiponectin as an insulin-sensitizer with potent anti-diabetic, anti-atherogenic, anti-inflammatory, and cardio-protective activities. Therefore, upregulation of endogenous adiponectin production by pharmacological and/or dietary interventions might have multiple beneficial effects on obesity-related disorders. A number of pharmacological agents that increase adiponectin production have recently been identified. Among them, the anti-diabetic actions of the PPARγ agonists, thiazolidinediones (TZDs), are mediated, at least in part, by induction of adiponectin expression. Here, we summarize the recent progress on clinical and pharmacological studies of adiponectin, and discuss the utility of adiponectin as a target to develop novel therapies for treatment and prevention of obesity-related metabolic and cardiovascular diseases. © 2006 Wiley-Liss, Inc.