Sankaralingam Sowndramalingam, Abo Alrob Osama, Zhang Liyan, Jaswal Jagdip S, Wagg Cory S, Fukushima Arata, Padwal Raj S, Johnstone David E, Sharma Arya M, Lopaschuk Gary D
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada Faculty of Pharmacy, Yarmouk University, Irbid, Jordan.
Diabetes. 2015 May;64(5):1643-57. doi: 10.2337/db14-1050. Epub 2014 Dec 18.
Recent studies suggest improved outcomes and survival in obese heart failure patients (i.e., the obesity paradox), although obesity and heart failure unfavorably alter cardiac function and metabolism. We investigated the effects of weight loss on cardiac function and metabolism in obese heart failure mice. Obesity and heart failure were induced by feeding mice a high-fat (HF) diet (60% kcal from fat) for 4 weeks, following which an abdominal aortic constriction (AAC) was produced. Four weeks post-AAC, mice were switched to a low-fat (LF) diet (12% kcal from fat; HF AAC LF) or maintained on an HF (HF AAC HF) for a further 10 weeks. After 18 weeks, HF AAC LF mice weighed less than HF AAC HF mice. Diastolic function was improved in HF AAC LF mice, while cardiac hypertrophy was decreased and accompanied by decreased SIRT1 expression, increased FOXO1 acetylation, and increased atrogin-1 expression compared with HF AAC HF mice. Insulin-stimulated glucose oxidation was increased in hearts from HF AAC LF mice, compared with HF AAC HF mice. Thus lowering body weight by switching to LF diet in obese mice with heart failure is associated with decreased cardiac hypertrophy and improvements in both cardiac insulin sensitivity and diastolic function, suggesting that weight loss does not negatively impact heart function in the setting of obesity.
近期研究表明，肥胖心力衰竭患者的预后和生存率有所改善（即肥胖悖论），尽管肥胖和心力衰竭会对心脏功能和代谢产生不利影响。我们研究了体重减轻对肥胖心力衰竭小鼠心脏功能和代谢的影响。通过给小鼠喂食高脂（HF）饮食（脂肪提供60%的千卡热量）4周来诱导肥胖和心力衰竭，之后进行腹主动脉缩窄（AAC）。AAC术后4周，将小鼠改为低脂（LF）饮食（脂肪提供12%的千卡热量；HF AAC LF）或继续维持HF饮食（HF AAC HF）10周。18周后，HF AAC LF小鼠的体重低于HF AAC HF小鼠。与HF AAC HF小鼠相比，HF AAC LF小鼠的舒张功能得到改善，心脏肥大减轻，同时SIRT1表达降低、FOXO1乙酰化增加、atrogin-1表达增加。与HF AAC HF小鼠相比，HF AAC LF小鼠心脏中胰岛素刺激的葡萄糖氧化增加。因此，在肥胖心力衰竭小鼠中通过改为LF饮食降低体重与心脏肥大减轻以及心脏胰岛素敏感性和舒张功能改善有关，这表明在肥胖情况下体重减轻不会对心脏功能产生负面影响。
