Improved energy homeostasis of the heart in the metabolic state of exercise
Improved energy homeostasis of the heart in the metabolic state of exercise
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DOI：
10.1152/ajpheart.2000.279.4.h1490
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发表时间：
2000-10-01
影响因子：
4.8
通讯作者：
Taegtmeyer, H
中科院分区：
文献类型：
--
作者：
Goodwin, GW;Taegtmeyer, H
我们推测，在运动中系统发展的代谢条件(高血乳酸和高非酯化脂肪酸)有利于心脏在收缩刺激期间的能量平衡。我们使用在生理负荷和主要能量底物水平下灌流的工作大鼠心脏，比较了在静息和运动系统代谢条件下(灌流液中低乳酸和高乳酸和非酯化脂肪酸)对急性从低到高工作转变的代谢和收缩反应。糖原保存是由于高能磷酸盐得到更好的维护，是高脂肪和高乳酸改善能量平衡的结果。我们通过工作负荷和总的β-氧化之间更紧密的耦合来解释这一结果。高脂肪和高乳酸的总脂肪酸氧化反映了呼吸中外源和内源脂肪利用率的增加，这表现为长链脂肪酰辅酶A酯(LCFA-COA)的增加以及甘油三酯对总β-氧化的贡献增加。甘油三酯的周转(合成和降解)似乎也增加了。尽管丙二酰辅酶A升高，但LCFA-COA升高导致总β氧化增加。由此产生的线粒体摄取LCFA-COAS的瓶颈刺激了甘油三酯的合成。我们的结果表明了以下几点。首先，丙二酰辅酶A和LCFA-COAS都可以测定心脏中的总脂肪酸氧化。其次，外周糖酵解和脂解的同时刺激可以改善运动时的心脏能量平衡。我们推测，高乳酸通过绕过脂肪酸施加的糖酵解障碍，作为从脂肪酸衍生的乙酰-辅酶A获得高三碳环酸循环通量所必需的抗逆底物来贡献有益效果。
We postulate that metabolic conditions that develop systemically during exercise (high blood lactate and high nonesterified fatty acids) are favorable for energy homeostasis of the heart during contractile stimulation. We used working rat hearts perfused at physiological workload and levels of the major energy substrates and compared the metabolic and contractile responses to an acute low-to-high work transition under resting versus exercising systemic metabolic conditions (low vs. high lactate and nonesterified fatty acids in the perfusate). Glycogen preservation, resulting from better maintenance of high-energy phosphates, was a consequence of improved energy homeostasis with high fat and lactate. We explained the result by tighter coupling between workload and total beta-oxidation. Total fatty acid oxidation with high fat and lactate reflected increased availability of exogenous and endogenous fats for respiration, as evidenced by increased long-chain fatty acyl-CoA esters (LCFA-CoAs) and by an increased contribution of triglycerides to total beta-oxidation. Triglyceride turnover (synthesis and degradation) also appeared to increase. Elevated LCFA-CoAs caused high total beta-oxidation despite increased malonyl-CoA. The resulting bottleneck at mitochondrial uptake of LCFA-CoAs stimulated triglyceride synthesis. Our results suggest the following. First, both malonyl-CoA and LCFA-CoAs determine total fatty acid oxidation in heart. Second, concomitant stimulation of peripheral glycolysis and lipolysis should improve cardiac energy homeostasis during exercise. We speculate that high lactate contributes to the salutary effect by bypassing the glycolytic block imposed by fatty acids, acting as an anaplerotic substrate necessary for high tricarbocylic acid cycle flux from fatty acid-derived acetyl-CoA.