Impaired long-chain fatty acid oxidation and contractile dysfunction in the obese Zucker rat heart
Impaired long-chain fatty acid oxidation and contractile dysfunction in the obese Zucker rat heart
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DOI：
10.2337/diabetes.51.8.2587
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发表时间：
2002-08-01
期刊：
影响因子：
7.7
通讯作者：
Taegtmeyer, H
中科院分区：
文献类型：
--
作者：
Young, ME;Guthrie, PH;Taegtmeyer, H
我们研究了心脏对脂肪酸可用性生理增加的反应性降低是否会导致脂质蓄积和脂毒性心脏病。瘦和肥胖Zucker大鼠自由进食或禁食过夜。空腹增加血浆非酯化脂肪酸水平在瘦和肥胖大鼠，虽然水平是最大的肥胖大鼠无论营养状况。尽管增加脂肪酸的可用性，过氧化物酶体增殖物激活受体（PPAR）-α调节基因的mRNA转录水平是相似的喂养瘦和喂养肥胖大鼠的心脏。禁食增加了所有PPAR-alpha调节基因在瘦Zucker大鼠心脏的表达，而在肥胖Zucker大鼠心脏，肌肉肉毒碱棕榈酰转移酶和中链酰基辅酶A脱氢酶与禁食不变。进食大鼠心脏的油酸氧化速率相似。然而，禁食增加油酸氧化率只在心脏从瘦大鼠。戏剧性的脂质沉积发生在心肌细胞的肥胖，但不瘦，Zucker大鼠禁食。与瘦大鼠相比，无论营养状况如何，肥胖大鼠心脏的心输出量明显降低。禁食只增加瘦大鼠心脏的心输出量。因此，心脏不能与增加的脂肪酸可用性成比例地增加脂肪酸氧化与肥胖Zucker大鼠的脂质积聚和收缩功能障碍相关。
We investigated whether decreased responsiveness of the heart to physiological increases in fatty acid availability results in lipid accumulation and lipotoxic heart disease. Lean and obese Zucker rats were either fed ad libitum or fasted overnight. Fasting increased plasma nonesterified fatty acid levels in both lean and obese rats, although levels were greatest in obese rats regardless of nutritional status. Despite increased fatty acid availability, the mRNA transcript levels of peroxisome proliferator-activated receptor (PPAR)-alpha-regulated genes were similar in fed lean and fed obese rat hearts. Fasting increased expression of all PPAR-alpha-regulated genes in lean Zucker rat hearts, whereas, in obese Zucker rat hearts, muscle carnitine palmitoyltransferase and medium-chain acyl-CoA dehydrogenase were unaltered with fasting. Rates of oleate oxidation were similar for hearts from fed rats. However, fasting increased rates of oleate oxidation only in hearts from lean rats. Dramatic lipid deposition occurred within cardiomyocytes of obese, but not lean, Zucker rats upon fasting. Cardiac output was significantly depressed in hearts isolated from obese rats compared with lean rats, regardless of nutritional status. Fasting increased cardiac output in hearts of lean rats only. Thus, the heart's inability to increase fatty acid oxidation in proportion to increased fatty acid availability is associated with lipid accumulation and contractile dysfunction of the obese Zucker rat.