Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand.
Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Metabolism. 2019 May;94:77-87. doi: 10.1016/j.metabol.2019.02.003. Epub 2019 Feb 21.
Long-term high-fat diet (HFD) consumption causes obese-insulin resistance which is known to be a major risk factor for cardiovascular diseases due to its impact on the impairment of left ventricular (LV) contractile function and cardiac mitochondrial function. Intracellular calcium [Ca]i regulation plays an important role in the maintenance of LV function. Although either caloric restriction (CR) or exercise (Ex) are shown to strongly affect metabolic status and LV function, the combined effects of exercise and calorie restriction on cardiometabolic status, cardiac mitochondrial dynamics and cardiac [Ca]i transient homeostasis under conditions of obese-insulin resistance have never been investigated.
Female rats were fed with either a high-fat diet (HFD: fat, 59.28%; protein, 26.45%; carbohydrate, 14.27%) or a normal diet (fat, 19.77%; protein, 28.24%; carbohydrate, 51.99%) for 13 weeks. HFD rats were then divided into 4 groups: 1) Vehicle (HFD + Veh); 2) Calorie restriction (HFD + CR); 3) Exercise (HFD + Ex) and 4) Combined therapy (HFD + CR + Ex). After 6-week intervention, the metabolic status, heart rate variability (HRV), LV function, cardiac mitochondrial dynamics, and [Ca]i transients were determined.
Insulin resistance developed in HFD rats as indicated by increased plasma insulin and HOMA index. Although HFD + Veh rats had markedly impaired LV function, indicated by reduced %LVFS and impaired cardiac mitochondrial dynamics and [Ca]i transients, these impairments were attenuated in the HFD + CR, HFD + Ex and HFD + CR + Ex rats. However, the greatest improvement in cardiometabolic function was observed in HFD + CR + Ex rats.
Our findings indicated that a combination of calorie restriction and exercise exerted greater cardioprotection than a monotherapy through the improvement of cardiometabolic status, cardiac mitochondrial dynamics and cardiac [Ca]i homeostasis in obese-insulin resistant rats.
长期高脂肪饮食（HFD）摄入会导致肥胖和胰岛素抵抗，这是心血管疾病的主要危险因素，因为它会损害左心室（LV）的收缩功能和心脏线粒体功能。细胞内钙 [Ca]i 调节在维持 LV 功能方面起着重要作用。尽管热量限制（CR）或运动（Ex）都被证明可以强烈影响代谢状态和 LV 功能，但运动和热量限制对肥胖和胰岛素抵抗条件下心脏代谢状态、心脏线粒体动力学和心脏 [Ca]i 瞬变动态平衡的联合影响尚未被研究。
雌性大鼠分别用高脂肪饮食（HFD：脂肪 59.28%；蛋白质 26.45%；碳水化合物 14.27%）或正常饮食（脂肪 19.77%；蛋白质 28.24%；碳水化合物 51.99%）喂养 13 周。然后，HFD 大鼠被分为 4 组：1）Vehicle（HFD+Veh）；2）热量限制（HFD+CR）；3）运动（HFD+Ex）和 4）联合治疗（HFD+CR+Ex）。干预 6 周后，测定代谢状态、心率变异性（HRV）、LV 功能、心脏线粒体动力学和 [Ca]i 瞬变。
胰岛素抵抗在 HFD 大鼠中发展，表现为血浆胰岛素和 HOMA 指数增加。尽管 HFD+Veh 大鼠的 LV 功能明显受损，表现为 %LVFS 降低和心脏线粒体动力学和 [Ca]i 瞬变受损，但这些损伤在 HFD+CR、HFD+Ex 和 HFD+CR+Ex 大鼠中得到了减轻。然而，在 HFD+CR+Ex 大鼠中观察到代谢功能的最大改善。
我们的研究结果表明，通过改善肥胖和胰岛素抵抗大鼠的心脏代谢状态、心脏线粒体动力学和心脏 [Ca]i 稳态，热量限制和运动的联合治疗比单一疗法具有更大的心脏保护作用。
