Obesogenic high fat western diet induces oxidative stress and apoptosis in rat heart.
Obesogenic high fat western diet induces oxidative stress and apoptosis in rat heart.
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DOI：
10.1007/s11010-010-0546-y
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发表时间：
2010-11
影响因子：
4.3
通讯作者：
Taegtmeyer, Heinrich
中科院分区：
文献类型：
--
作者：
Ballal, Kalpana;Wilson, Christopher R.;Harmancey, Romain;Taegtmeyer, Heinrich
关键词：
给Wistar大鼠喂食高热量的“西方”饮食（45%脂肪）长达48周诱导肥胖和心脏功能障碍，而高脂肪饮食（60%脂肪）仅诱导肥胖。在这里，我们研究了心脏中两种形式的饮食诱导肥胖的分子“足迹”。在长期喂食西方饮食的大鼠中，苹果酸酶的心脏mRNA转录水平下降（-72%，p<0.05），表明克雷布斯循环的回补通量受损和线粒体功能障碍。此外，转录因子MEF 2C（肌细胞增强因子2C）及其靶基因SERCA 2a（肌浆网Ca 2 +-ATP酶）的表达显著降低。氧化应激反映在锰超氧化物歧化酶，谷胱甘肽过氧化物酶1的转录水平降低和线粒体转录因子A的蛋白质水平增加，这表明在面对线粒体损伤增加的补偿线粒体生物合成。氧化损伤伴随着蛋白质糖基化增加，谷氨酰胺果糖6-磷酸酰胺转移酶2的转录水平增加和乙酰辅酶A羧化酶的蛋白质水平降低。最后，凋亡是明显的TUNEL阳性和升高的mRNA转录水平和caspase 3的活性。与这些结果一致，Bcl 2的蛋白水平显著降低。我们的结论是，由于苹果酸酶水平降低，MEF 2C及其靶基因SERCA 2a下调，氧化应激和程序性细胞死亡的克雷布斯循环中间体的补充不足，都是心脏收缩功能障碍的潜在因素。
Feeding Wistar rats a high calorie “Western” diet (45% fat) for up to 48 weeks induces obesity and cardiac dysfunction, while a high fat diet (60% fat) induces obesity only. Here we investigated the molecular “footprints” of the two forms of diet-induced obesity in the heart. In rats fed Western diet for a long term, cardiac mRNA transcript levels of malic enzyme were decreased (−72%, p<0.05), suggesting impaired anaplerotic flux of the Krebs cycle and mitochondrial dysfunction. Additionally, there was a marked decrease in the expression of the transcription factor MEF2C (myocyte enhancer factor 2C) and its target gene SERCA2a (sarco-endo-plasmic reticulum Ca2+-ATPase). Oxidative stress was reflected in reduced transcript levels of manganese superoxide dismutase, glutathione peroxidase 1 and increased protein levels of mitochondrial transcription factor A, suggesting compensatory mitochondrial biogenesis in the face of increased mitochondrial damage. Oxidant injury was accompanied by increased protein glycosylation, increased transcript levels of glutamine fructose 6-phosphate amidotransferase 2 and decreased protein levels of acetyl Co-A carboxylase. Lastly, apoptosis was evident by TUNEL positivity and elevated mRNA transcript levels and activity of caspase 3. Consistent with these results, protein levels of Bcl2 were markedly reduced. We conclude that inadequate supplementation of Krebs cycle intermediates due to reduced levels of malic enzyme, downregulation of MEF2C and its target gene SERCA2a, oxidative stress and programmed cell death are all potential contributors to contractile dysfunction of the heart.
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影响因子：
4.8
作者：
Nagle, Cynthia A.;An, Jie;Coleman, Rosalind A.
通讯作者：
Coleman, Rosalind A.
影响因子：
37.8
作者：
Razeghi, P;Young, ME;Taegtmeyer, H
通讯作者：
Taegtmeyer, H
影响因子：
5.1
作者：
Byrne, M. J.;Power, J. M.;Kaye, D. M.
通讯作者：
Kaye, D. M.
影响因子：
5.9
作者：
Leichman, Joshua G.;Wilson, Erik B.;Taegtmeyer, Heinrich
通讯作者：
Taegtmeyer, Heinrich
影响因子：
3.7
作者：
KAJSTURA, J;MANSUKHANI, M;ANVERSA, P
通讯作者：
ANVERSA, P