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 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 (CR) (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 it decreased cardiac hypertrophy post TAC (left ventricle mass was 168 +/- 7 and 171 +/- 10 mg in HF TAC LF and HF TAC CR mice, respectively, vs 210 +/- 8 mg in HF TAC mice, P < 0.05). Weight loss enhanced cardiac insulin signalling, insulin-stimulated glucose oxidation rates (1.5 +/- 0.1 and 1.5 +/- 0.1 mu mol/g dry wt/min in HF TAC LF and HF TAC CR mice, respectively, vs 0.2 +/- 0.1 mu mol/g dry wt/min in HF TAC mice, P < 0.05) and it decreased pyruvate dehydrogenase phosphorylation. Cardiac fatty acid oxidation rates, AMPK(Tyr172)/ACC(Ser79) signalling 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.