高脂喂养诱导心力衰竭心肌胰岛素抵抗与收缩功能保存有关。
Myocardial insulin resistance induced by high fat feeding in heart failure is associated with preserved contractile function.
机构信息
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.
出版信息
Am J Physiol Heart Circ Physiol. 2010 Dec;299(6):H1917-27. doi: 10.1152/ajpheart.00687.2010. Epub 2010 Sep 17.
Previous studies have reported that high fat feeding in mild to moderate heart failure (HF) results in the preservation of contractile function. Recent evidence has suggested that preventing the switch from fatty acid to glucose metabolism in HF may ameliorate dysfunction, and insulin resistance is one potential mechanism for regulating substrate utilization. This study was designed to determine whether peripheral and myocardial insulin resistance exists with HF and/or a high-fat diet and whether myocardial insulin signaling was altered accordingly. Rats underwent coronary artery ligation (HF) or sham surgery and were randomized to normal chow (NC; 14% kcal from fat) or a high-fat diet (SAT; 60% kcal from fat) for 8 wk. HF + SAT animals showed preserved systolic (+dP/dt and stroke work) and diastolic (-dP/dt and time constant of relaxation) function compared with HF + NC animals. Glucose tolerance tests revealed peripheral insulin resistance in sham + SAT, HF + NC, and HF + SAT animals compared with sham + NC animals. PET imaging confirmed myocardial insulin resistance only in HF + SAT animals, with an uptake ratio of 2.3 ± 0.3 versus 4.6 ± 0.7, 4.3 ± 0.4, and 4.2 ± 0.6 in sham + NC, sham + SAT, and HF + NC animals, respectively; the myocardial glucose utilization rate was similarly decreased in HF + SAT animals only. Western blot analysis of insulin signaling protein expression was indicative of cardiac insulin resistance in HF + SAT animals. Specifically, alterations in Akt and glycogen synthase kinase-3β protein expression in HF + SAT animals compared with HF + NC animals may be involved in mediating myocardial insulin resistance. In conclusion, HF animals fed a high-saturated fat exhibited preserved myocardial contractile function, peripheral and myocardial insulin resistance, decreased myocardial glucose utilization rates, and alterations in cardiac insulin signaling. These results suggest that myocardial insulin resistance may serve a cardioprotective function with high fat feeding in mild to moderate HF.
先前的研究报告指出，在轻度至中度心力衰竭（HF）中，高脂肪喂养可保留收缩功能。最近的证据表明，预防 HF 中脂肪酸向葡萄糖代谢的转变可能改善功能障碍，而胰岛素抵抗是调节底物利用的潜在机制之一。本研究旨在确定 HF 和/或高脂肪饮食是否存在外周和心肌胰岛素抵抗，以及心肌胰岛素信号是否相应改变。大鼠接受冠状动脉结扎（HF）或假手术，并随机分为正常饮食（NC；14%的热量来自脂肪）或高脂肪饮食（SAT；60%的热量来自脂肪）8 周。与 HF + NC 动物相比，HF + SAT 动物的收缩功能（+dP/dt 和冲程功）和舒张功能（-dP/dt 和松弛时间常数）均得到保留。与 sham + NC 动物相比，sham + SAT、HF + NC 和 HF + SAT 动物的葡萄糖耐量试验均显示出外周胰岛素抵抗。PET 成像仅在 HF + SAT 动物中证实存在心肌胰岛素抵抗，摄取率分别为 2.3 ± 0.3、4.6 ± 0.7、4.3 ± 0.4 和 4.2 ± 0.6，而 sham + NC、sham + SAT 和 HF + NC 动物分别为 4.2 ± 0.6；仅在 HF + SAT 动物中，心肌葡萄糖利用率也类似降低。胰岛素信号蛋白表达的 Western blot 分析表明，HF + SAT 动物存在心脏胰岛素抵抗。具体而言，与 HF + NC 动物相比，HF + SAT 动物的 Akt 和糖原合酶激酶-3β蛋白表达的改变可能参与介导心肌胰岛素抵抗。总之，给予高脂肪的 HF 动物表现出保留的心肌收缩功能、外周和心肌胰岛素抵抗、心肌葡萄糖利用率降低以及心脏胰岛素信号改变。这些结果表明，在轻度至中度 HF 中，高脂肪喂养可能导致心肌胰岛素抵抗，从而发挥心脏保护作用。
Zotero 插件