Metabolic Adaptation Follows Contractile Dysfunction in the Heart of Obese Zucker Rats Fed a High-Fat "Western" Diet
Metabolic Adaptation Follows Contractile Dysfunction in the Heart of Obese Zucker Rats Fed a High-Fat "Western" Diet
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DOI：
10.1038/oby.2009.500
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发表时间：
2010-10-01
期刊：
影响因子：
6.9
通讯作者：
Taegtmeyer, Heinrich
中科院分区：
文献类型：
--
作者：
Burgmaier, Mathias;Sen, Shiraj;Taegtmeyer, Heinrich
正常心脏通过改变供能底物的相对氧化率来对其代谢环境的变化做出反应。我们假设，当遗传性肥胖的老鼠被喂食高热量、高脂肪的“西方”饮食（WD）时，这种灵活性就会丧失。雄性 Zucker 肥胖 (ZO) 和 Zucker 瘦 (ZL) 大鼠分别喂食由 10 kcal% 和 45 kcal% 脂肪组成的对照或 WD 7 或 28 天。原位测量心脏甘油三酯和 mRNA 转录物水平。离体测量底物氧化速率和心脏功率。喂食 WD 7 天的 ZO 大鼠的心脏显示出心脏功率下降和心脏甘油三酯含量增加，但油酸氧化率或丙酮酸脱氢酶激酶 4 (PDK-4)、解偶联蛋白 3 (UCP-3)、线粒体 (MTE-1) 和胞质硫酯酶 - 1 (CTE-1) 的 mRNA 转录水平没有变化。当喂食 WD 28 天时，与仅喂食相同饮食 7 天的 ZO 大鼠相比，ZO 大鼠的心脏功率没有进一步下降，心肌内甘油三酯水平没有进一步增加，但油酸氧化率和 CTE-1、MTE-1、PDK-4 和 UCP-3 转录水平显着增加。相比之下，喂食 WD 的 ZL 大鼠的心脏显示油酸氧化率增加，所研究的脂肪酸反应基因的转录水平增加，并且收缩功能没有进一步恶化。我们得出的结论是，将肥胖遗传模型暴露于WD的营养应激下会导致心脏代谢灵活性的早期可逆性丧失，并伴有收缩功能障碍。
The normal heart responds to changes in its metabolic milieu by changing relative oxidation rates of energy-providing substrates. We hypothesized that this flexibility is lost when genetically obese rats are fed a high-caloric, high-fat "Western" diet (WD). Male Zucker obese (ZO) and Zucker lean (ZL) rats were fed either control or WD composed of 10 kcal% and 45 kcal% fat, respectively, for 7 or 28 days. Cardiac triglycerides and mRNA transcript levels were measured in situ. Substrate oxidation rates and cardiac power were measured ex vivo. Hearts from ZO rats fed WD for 7 days showed decreased cardiac power and increased cardiac triglyceride content, but no change in oleate oxidation rates or mRNA transcript levels of pyruvate dehydrogenase kinase-4 (PDK-4), uncoupling protein-3 (UCP-3), and mitochondrial (MTE-1) and cytosolic thioesterase-1(CTE-1). When fed WD for 28 days, ZO rats showed no further decrease in cardiac power and no further increase in intramyocardial triglyceride levels compared to ZO rats fed the same diet for 7 days only, but did show significantly increased oleate oxidation rates and transcript levels of CTE-1, MTE-1, PDK-4, and UCP-3. In contrast, hearts from ZL rats fed WD showed increased rates of oleate oxidation and increased transcript levels of the fatty acid responsive genes investigated, and no further deterioration of contractile function. We conclude that exposing a genetic model of obesity to the nutrient stress of WD results in an early reversible loss of metabolic flexibility of the heart that is accompanied by contractile dysfunction.