Weight Loss Enhances Cardiac Energy Metabolism and Function in Heart Failure Associated with Obesity

Aims: Obesity is associated with high rates of cardiac fatty acid oxidation, low rates of glucose oxidation, cardiac hypertrophy, and heart failure. Whether weight loss can lessen the severity of heart failure associated with obesity is not known. We therefore determined the effect of weight loss on cardiac energy metabolism and the severity of heart failure in obese mice with heart failure. Materials and Methods: Obesity and heart failure were induced by feeding mice a high-fat (HF) diet and subjecting them to a transverse aortic constriction (TAC). Obese mice with heart failure were then switched for 8 weeks to either a low-fat (LF) diet (HF TAC LF) or caloric restriction (40% caloric intake reduction, HF TAC CR) to induce weight loss. Results: Weight loss improved cardiac function (%EF was 38±6 and 36±6% in HF TAC LF and HF TAC CR mice vs 25±3% in HF TAC mice, p<0.05) and decreased cardiac hypertrophy post-TAC (left ventricle mass was 168±7 and 171±10 mg in HF TAC LF and HF TAC CR mice vs 210±8 mg in HF TAC mice, p<0.05). Weight loss enhanced cardiac insulin signaling, insulin-stimulated glucose oxidation rates (1.5±0.1 and 1.5±0.1 µmol.g dry wt-1.min-1 in HF TAC LF, HF TAC CR mice vs 0.2±0.1 µmol.g dry wt-1.min-1 in HF TAC mice, p<0.05) and decreased pyruvate dehydrogenase phosphorylation. Cardiac fatty acid oxidation rates, AMPKTyr172/ACCSer79 signaling and the acetylation of ß-oxidation enzymes were attenuated following weight loss. Conclusions: Weight loss is an effective intervention to improve cardiac function and energy metabolism in heart failure associated with obesity.