Recent evidence points to molecules secreted by the adipose tissue, or adipokines, as possible links between increased adipose mass and metabolic abnormalities. Among these molecules, adiponectin has drawn much attention because of its insulin-sensitizing and antiatherogenic actions, suggesting that genetic deficits in its production or action may contribute to insulin resistance and coronary artery disease (CAD). A meta-analysis of the data published to date supports this hypothesis. Two independent effects, corresponding to the two linkage disequilibrium blocks that can be identified at the adiponectin locus, appear to be present. In the 5 block, the g.؊11391G3 A variant has a modest but significant effect on adiponectinemia, with a mean difference between genotypes of 1.64 ng/ml (95% CI 0.88 -2.41). In the 3 block, the g. O ur view of adipose tissue has undergone dramatic changes over the past 15 years. Previously believed to be a mere energy depot, adipose tissue is now considered a major endocrine organ regulating whole-body metabolism as well as inflammatory and immune responses (1,2). These actions are mediated by a number of molecules-collectively known as adipokines-that are secreted by adipocytes and act in an autocrine, paracrine, or endocrine fashion, adapting metabolic fluxes to the amount of stored energy (1,2). The discovery of such endocrine function of the adipose tissue has prompted the hypothesis that a genetic dysregulation of the adipokine network may contribute to the pathogenesis of insulin resistance and related disorders such as type 2 diabetes and cardiovascular disease. Of all the molecules that have been shown to be produced by the adipose tissue, adiponectin has drawn special attention, largely due to its effects on both insulin sensitivity and inflammation, and the fact that its expression and serum levels can be modulated by peroxisome proliferatoractivated receptor (PPAR)-␥ agonists drugs (Fig. 1). In this article, we will review the evidence that has been thus far gathered on the role of genetic variants in the adiponectin and adiponectin receptors genes as modulators of adiponectin-circulating levels and susceptibility to insulin resistance traits. We will also discuss the directions in which research on this topic is heading.
ADIPONECTIN: A SALUTARY ADIPOKINEAdiponectin, also known as adipocyte complement-related protein 30 (Acrp30), gelatin-binding protein 28 (Gbp28), adipose most abundant transcript 1(apM1), or AdipoQ, is exclusively produced by adipocytes (3-6). It is abundantly present in serum, where it circulates in two higher-order forms: a low-molecular weight dimer of trimers and a larger high-molecular weight complex of 12-18 subunits (7). Serum levels are 15% higher in women than in men (8). Data from both animal and human studies indicate that adiponectin has insulin-enhancing as well as anti-inflammatory actions (rev. in 9). Adiponectin levels are markedly reduced in obese/diabetic mice, and injection of the adiponectin globular domain to these animals ameliorates ...