Fig. 1 A hypothetical model for the secretion and action of adiponectin. The synthesis and secretion of adiponectin is increased by activation of the nuclear receptor PPAR-γ, and reduced by caloric excess, presumably associated with leptin deficiency or resistance. Once released, adiponectin can directly increase fatty-acid transport, oxidation and dissipation in skeletal muscle, reducing the levels of intramyocellular lipids, thus improving insulin signaling. The protein can also increase the sensitivity of the hepatocyte to insulin, either through a direct action, or indirectly by lowering circulating lipids due to its action on muscle. Thus, administration of adiponectin can result in improved insulin sensitivity and glucose tolerance, and can correct hyperglycemia associated with obesity.