ABSTRACT
Obesity is associated with development of insulin resistance, diabetes, cardiovascular disease and hypertension, but the basis of these associations is presently unclear. Since the discovery of leptin in the early 1990s, our view of adipose tissue has changed dramatically. Once thought of as strictly an energy repository, fat cells have emerged as an active player in energy homeostasis, producing a variety of signaling molecules (adipokines) that appear to play essential roles in metabolic, immune, cardiovascular, and endocrine regulation. Adiponectin (ADP) is a fat cell-derived peptide that acts as an insulin-sensitizing hormone (Scherer et al. 1995, Kadowaki and Yamauchi 2005), the circulating concentrations of which are inversely correlated with adipose tissue mass. ADP concentrations are also reduced in obesity-related diseases such as insulin resistance and the metabolic syndrome. Treatment with ADP lowers hepatic gluconeogenesis, serum glucose and ameliorates insulin resistance in mice (Combs et al. 2001, Yamauchi et al. 2001, Kadowaki and Yamauchi 2005). Transgenic mice over-expressing the globular portion of ADP demonstrate increased fatty acid clearance and insulin sensitivity (Combs et al. 2004). Conversely, ADP knockout mice demonstrate obesity, impaired insulin sensitivity, impaired fatty acid clearance, and hypertension (Kubota et al. 2002). Human genetic studies indicate that alterations in ADP signaling may lead to susceptibility to obesity, insulin resistance, diabetes and hypertension (Kadowaki and Yamauchi 2005). Collectively these observations suggest important roles for ADP in maintaining a variety of normal metabolic functions.
