Stearoyl-CoA desaturase-1 (SCD1) augments saturated fatty acid-induced lipid accumulation and inhibits apoptosis in cardiac myocytes.
Stearoyl-CoA desaturase-1 (SCD1) augments saturated fatty acid-induced lipid accumulation and inhibits apoptosis in cardiac myocytes.
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DOI：
10.1371/journal.pone.0033283
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kurabayashi M
中科院分区：
文献类型：
--
作者：
Matsui H;Yokoyama T;Sekiguchi K;Iijima D;Sunaga H;Maniwa M;Ueno M;Iso T;Arai M;Kurabayashi M
心肌对长链脂肪酸的摄取和利用不匹配，导致细胞内脂肪酸浓度异常高，最终导致心肌功能障碍。硬脂酰辅酶A脱饱和酶-1(SCD1)是一种将饱和脂肪酸(SFA)转化为单不饱和脂肪酸的限速酶。先前的研究表明，SCD1基因缺陷的小鼠可以免受胰岛素抵抗和饮食诱导的肥胖的影响；然而，SCD1在心脏中的作用仍有待确定。我们检测了3个月高蔗糖饮食诱导的肥胖大鼠心脏中SCD1的表达。我们还检测了在SFA存在的情况下，SCD1对新生大鼠心肌细胞能量代谢和凋亡细胞死亡的影响。在这里，我们发现，在喂食高蔗糖饮食的大鼠心脏中，SCD1的表达增加了3.6倍，而成脂基因的表达没有明显的变化。强迫表达SCD1增加了棕榈酸诱导的脂肪堆积，但减弱了过量的脂肪酸氧化，并恢复了减少的葡萄糖氧化。重要的是，SCD1显著抑制了SFA诱导的caspase3的激活、神经酰胺的合成、二酰甘油的合成、细胞凋亡和线粒体活性氧物种(ROS)的产生。使用SCD1siRNA的实验证实了这些观察结果。此外，我们还发现，心肌细胞暴露在葡萄糖和胰岛素中可以诱导SCD1的表达。我们的结果表明，SCD1受到心脏代谢综合征成分的高度调控，这种SCD1的诱导有助于缓解SFA诱导的不利脂肪酸分解代谢，并最终阻止SFA诱导的细胞凋亡。
Mismatch between the uptake and utilization of long-chain fatty acids in the myocardium leads to abnormally high intracellular fatty acid concentration, which ultimately induces myocardial dysfunction. Stearoyl-Coenzyme A desaturase-1 (SCD1) is a rate-limiting enzyme that converts saturated fatty acids (SFAs) to monounsaturated fatty acids. Previous studies have shown that SCD1-deficinent mice are protected from insulin resistance and diet-induced obesity; however, the role of SCD1 in the heart remains to be determined. We examined the expression of SCD1 in obese rat hearts induced by a sucrose-rich diet for 3 months. We also examined the effect of SCD1 on myocardial energy metabolism and apoptotic cell death in neonatal rat cardiac myocytes in the presence of SFAs. Here we showed that the expression of SCD1 increases 3.6-fold without measurable change in the expression of lipogenic genes in the heart of rats fed a high-sucrose diet. Forced SCD1 expression augmented palmitic acid-induced lipid accumulation, but attenuated excess fatty acid oxidation and restored reduced glucose oxidation. Of importance, SCD1 substantially inhibited SFA-induced caspase 3 activation, ceramide synthesis, diacylglycerol synthesis, apoptotic cell death, and mitochondrial reactive oxygen species (ROS) generation. Experiments using SCD1 siRNA confirmed these observations. Furthermore, we showed that exposure of cardiac myocytes to glucose and insulin induced SCD1 expression. Our results indicate that SCD1 is highly regulated by a metabolic syndrome component in the heart, and such induction of SCD1 serves to alleviate SFA-induced adverse fatty acid catabolism, and eventually to prevent SFAs-induced apoptosis.
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影响因子：
4.2
作者：
Miyazaki, M;Man, WC;Ntambi, JM
通讯作者：
Ntambi, JM
影响因子：
29
作者：
Hulver, MW;Berggren, JR;Muoio, DM
通讯作者：
Muoio, DM
影响因子：
4.8
作者：
Miyazaki, M;Kim, YC;Ntambi, JM
通讯作者：
Ntambi, JM
DOI：
10.1073/pnas.132384699
发表时间：
2002-08-20
影响因子：
11.1
作者：
Ntambi, JM;Miyazaki, M;Attie, AD
通讯作者：
Attie, AD
影响因子：
15.9
作者：
Gutierrez-Juarez, Roger;Pocai, Alessandro;Rossetti, Luciano
通讯作者：
Rossetti, Luciano