Endocrine functions of adipose tissue: focus on adiponectin.

Accumulating evidence indicates that obesity and overweight are associated with, and contribute to, the development of type 2 diabetes mellitus (DM), cardiovascular disease (CVD), and chronic kidney disease (CKD). The adipocyte-derived cytokine, adiponectin, has been shown to improve insulin sensitivity, increase rates of fatty acid oxidation, decrease muscle lipid content, and reduce inflammation and vascular injury. However, adiponectin levels have been found to be reduced in persons with obesity and type 2 DM. Furthermore, adiponectin levels are inversely associated with those of tumor necrosis factor-alpha and C-reactive protein-markers of endothelial dysfunction and systemic inflammation. The 2 receptors for adiponectin-Adipo R(1) and Adipo R(2), which are expressed in muscle and liver tissue and in human fat cells-are hormonally regulated, with increased insulin levels causing a reduction in their abundance. The hyperinsulinemia observed in obesity, therefore, may be partially responsible for the reduction in the numbers of adiponectin receptors. Adiponectin aggregates range from a hexamer of low molecular weight to larger multimeric structures of high molecular weight. A smaller proteolytic fragment-the globular head domain of adiponectin, or gAd-interacts specifically with skeletal muscle. The relation of circulating adiponectin to its biologic actions is more complex than originally believed; therefore, it is the multimeric forms of the adiponectin molecule that need to be measured and evaluated in relation to associated metabolic, cardiovascular, and renal functions. Furthermore, strategies to measure the numbers of adiponectin receptors on available tissue need to be developed to fully assess the clinical role of adiponectin in type 2 DM, CVD, and CKD.