Abstract 452: Signal Transducer and Activator of Transcription 4 Deficiency Improves the Metabolic Phenotype and Skeletal Muscle Insulin Signaling in LDLr-/- Mice on Diabetogenic High-Cholesterol Diet

Insulin resistance and type2 diabetes are associated with increased incidence of cardiovascular disease. About 80% of the subjects with type2 diabetes die due to cardiovascular complications. We previously showed that STAT4 deficiency improves insulin resistance in C57Bl6 mice on high fat diet and STAT4-/-ApoE-/- mice develop significantly lower atherosclerosis compared to ApoE-/- controls. The goal of this project was to determine the effect of STAT4 deficiency in a combined model of atherosclerosis and insulin resistance. To this purpose we generated STAT4-/-LDLr-/- mice and fed them either a chow diet or a high carbohydrate (36.6%), high cholesterol (0.15%) (DDC) diet for 16 weeks (n=7-10). The LDLr-/- on DDC diet developed glucose intolerance and insulin resistance as well as atherosclerosis and hypercholesterolemia compared to chow fed controls. STAT4-/-LDLr-/- mice on DDC diet, although hypercholesterolemic had significantly reduced atherosclerotic plaques by en face staining (p<0.05). Also STAT4 de...