Role of insulin resistance in heart failure and high fat diet

Abstract

Both heart failure (HF) and high saturated fat diets (SAT) are associated with the development of insulin resistance. Whether insulin resistance exists in a model that involves both HF+SAT has not been studied. Previous studies reported that HF+SAT rats have improved left ventricular contractile and mitochondrial function compared to HF animals fed normal chow (NC). We hypothesize that myocardial insulin resistance exists in HF+SAT rats and that it serves a cardioprotective role. Male Wistar rats underwent coronary ligation or sham surgery and were fed NC (10% kcal fat) or SAT (60% kcal saturated fat) for 8 weeks. Five weeks post ligation, a glucose tolerance test (GTT) was performed to determine peripheral insulin resistance via plasma glucose and insulin concentrations. Echocardiography was done at 7 weeks post ligation to assess cardiac function. Tissue was harvested 8 weeks post ligation to assess the insulin signaling pathway via targets such as AKT, mTOR, GSK3β, eIF‐2, and AMPK by protein and RNA analysis. Preliminary results indicate that HF+NC and Sham+SAT have abnormal GTTs compared to Sham+NC. However, HF+SAT animals do not have impaired GTT. Ongoing studies will assess whether differences in GTT result from alterations in insulin signaling and whether these alterations in HF+SAT serve in a cardioprotective function in heart failure. (Grant # NHLBI HL‐081857 & AHA 0535361N)