Characterization of nuclear protein binding (AP-1, GR, and STAT) in the genetically obese (fa/fa) Zucker rat

There is evidence to suggest that obese populations have an increased susceptibility to various pathologic disorders. Both AP-1 and STAT nuclear binding proteins have been suggested to play a role in certain obesity-related diseases. The objective of our studies reported herein was to compare constitutive binding activity of nuclear proteins (AP-1, GR, and STAT), that may be relevant to obesity-related diseases in the obese (fa/fa) Zucker rat to lean (Fa/?) littermates. AP-1, GR, and STAT liver nuclear protein binding activity was analyzed using the electrophoretic mobility shift assay (EMSA). EMSA analysis of liver nuclear protein from obese and lean Zucker rats revealed high constitutive AP-1 binding activity in the obese animals. AP-1 binding activity in the obese rats was not further elevated by treatment with phenobarbital, a known inducer of AP-1 binding activity. No differences were observed in GR binding to a consensus GRE between obese and lean animals; however, STAT binding activity to a consensus GAS element was lower in liver tissue from obese Zucker rats. Our findings presented herein suggest that the fa/fa Zucker rat may be a suitable obese rodent model for studying the roles AP-1 and STAT may play in the pathologies of these diseases.