Saddik M, Lopaschuk G D
Cardiovascular Disease Research Group, University of Alberta, Edmonton, Canada.
J Biol Chem. 1992 Feb 25;267(6):3825-31.
Triglyceride turnover in reperfused/ischemic rat hearts was investigated. Hearts were initially perfused under aerobic conditions for a 1-h "pulse" perfusion with 1.2 mM [1-14C]palmitate to label the endogenous lipid pools, followed by a 30-min period of no-flow ischemia or a 10-min period of retrograde perfusion (control). Hearts were then reperfused under aerobic conditions with buffer containing 1.2 mM [9,10-3H]palmitate. All buffers contained 11 mM glucose and 500 microunits/ml insulin. Rates of endogenous triglyceride lipolysis and synthesis were measured during reperfusion, whereas rates of exogenous palmitate oxidation were measured both prior to ischemia and during reperfusion following ischemia. During reperfusion of ischemic hearts, a 20% increase in exogenous fatty acid oxidation rates was seen compared with pre-ischemic rates. Despite an initial burst of endogenous fatty acid oxidation, no acceleration of steady state endogenous triglyceride lipolysis was seen compared with their nonischemic hearts. In contrast, a significant increase in triglyceride synthesis was observed. Triglyceride turnover was also measured in a series of hearts reperfused following ischemia in the absence of exogenous fatty acids. A significant enhancement of functional recovery was seen compared with hearts reperfused with 1.2 mM palmitate. In addition, a significant increase in fatty acid oxidation from endogenous triglyceride lipolysis was observed. We conclude that the heart quickly recovers its ability to oxidize exogenous fatty acids during reperfusion and that although triglyceride lipolysis is not accelerated during reperfusion of ischemic hearts in the presence of 1.2 mM palmitate, a significant increase in triglyceride synthesis does occur.
研究了再灌注/缺血大鼠心脏中的甘油三酯周转率。心脏首先在有氧条件下用1.2 mM [1-14C]棕榈酸进行1小时的“脉冲”灌注，以标记内源性脂质池，随后进行30分钟的无血流缺血或10分钟的逆行灌注（对照）。然后心脏在有氧条件下用含有1.2 mM [9,10-3H]棕榈酸的缓冲液进行再灌注。所有缓冲液均含有11 mM葡萄糖和500微单位/毫升胰岛素。在再灌注期间测量内源性甘油三酯的脂解和合成速率，而在缺血前和缺血后再灌注期间测量外源性棕榈酸的氧化速率。在缺血心脏的再灌注期间，与缺血前速率相比，外源性脂肪酸氧化速率增加了20%。尽管内源性脂肪酸氧化有一个初始爆发，但与非缺血心脏相比，稳态内源性甘油三酯脂解没有加速。相反，观察到甘油三酯合成有显著增加。还在一系列缺血后再灌注且无外源性脂肪酸的心脏中测量了甘油三酯周转率。与用1.2 mM棕榈酸再灌注的心脏相比，功能恢复有显著增强。此外，观察到内源性甘油三酯脂解产生的脂肪酸氧化有显著增加。我们得出结论，心脏在再灌注期间迅速恢复其氧化外源性脂肪酸的能力，并且尽管在存在1.2 mM棕榈酸的情况下缺血心脏再灌注期间甘油三酯脂解没有加速，但甘油三酯合成确实有显著增加。
