Decreased circulating adiponectin levels are associated with decreased insulin sensitivity and are an independent risk factor for the development of related complications, such as visceral obesity and hepatic steatosis. In addition, positive response to thiazolidinedione (TZD) treatment in insulin resistant/diabetic patients has been shown to correlate with improvements in adiponectin levels and/or activity. Thus the central hypothesis of this proposal is that transgenic overexpression of adiponectin will ameliorate or prevent the development of insulin resistance, diabetes and related complications in male GLUT 4 heterozygous knockout mice (G4 ). The male G4 mouse develops insulin resistance, diabetes, visceral obesity and hepatic steatosis all of which are proceeded by decreased adiponectin levels. We will test the effects on adiponectin overexpression upon the development of these conditions in the G4 mouse. Furthermore, we will examine the expression pattern of several candidate genes suspected of contributing to these conditions. Finally, we will test the role of adiponectin in conferring the beneficial effects of TZD treatment by using G4 lacking a functional adiponectin gene treated without or with TZDs.
