Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada.
Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Diabetes Obes Metab. 2019 Aug;21(8):1944-1955. doi: 10.1111/dom.13762. Epub 2019 Jun 4.
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.
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.
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 μmol/g dry wt/min in HF TAC LF and HF TAC CR mice, respectively, vs 0.2 ± 0.1 μmol/g dry wt/min in HF TAC mice, P < 0.05) and it decreased pyruvate dehydrogenase phosphorylation. Cardiac fatty acid oxidation rates, AMPK /ACC signalling and the acetylation of ß-oxidation enzymes, were attenuated following weight loss.
Weight loss is an effective intervention to improve cardiac function and energy metabolism in heart failure associated with obesity.
肥胖与心脏脂肪酸氧化率高、葡萄糖氧化率低、心脏肥大和心力衰竭有关。减肥是否能减轻肥胖相关心力衰竭的严重程度尚不清楚。因此，我们测定了减肥对肥胖合并心力衰竭小鼠心脏能量代谢和心力衰竭严重程度的影响。
通过高脂饮食喂养和主动脉缩窄（TAC）使小鼠肥胖和心力衰竭，然后将肥胖合并心力衰竭的小鼠在 8 周内切换至低脂（LF）饮食（HF TAC LF）或热量限制（CR）（减少 40%热量摄入，HF TAC CR）以诱导体重减轻。
体重减轻改善了心功能（%EF 在 HF TAC LF 和 HF TAC CR 小鼠中分别为 38±6%和 36±6%，而 HF TAC 小鼠中为 25±3%，P<0.05），并减少了 TAC 后的心脏肥大（左心室质量在 HF TAC LF 和 HF TAC CR 小鼠中分别为 168±7 和 171±10mg，而 HF TAC 小鼠中为 210±8mg，P<0.05）。体重减轻增强了心脏胰岛素信号，胰岛素刺激的葡萄糖氧化率（HF TAC LF 和 HF TAC CR 小鼠中分别为 1.5±0.1 和 1.5±0.1μmol/g 干重/min，而 HF TAC 小鼠中为 0.2±0.1μmol/g 干重/min，P<0.05），并降低了丙酮酸脱氢酶磷酸化。体重减轻后，心脏脂肪酸氧化率、AMPK/ACC 信号和β-氧化酶的乙酰化均减弱。
减肥是改善肥胖相关心力衰竭患者心功能和能量代谢的有效干预措施。
