Mouse SIRT3 attenuates hypertrophy-related lipid accumulation in the heart through the deacetylation of LCAD.
Mouse SIRT3 attenuates hypertrophy-related lipid accumulation in the heart through the deacetylation of LCAD.
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DOI：
10.1371/journal.pone.0118909
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Bu P
中科院分区：
文献类型：
--
作者：
Chen T;Liu J;Li N;Wang S;Liu H;Li J;Zhang Y;Bu P
心脏肥大是对压力、容量应激和既往梗死后收缩质量损失的适应性反应。心肌肥厚的代谢变化包括脂肪酸氧化抑制和葡萄糖利用增强，这可能导致脂质在心脏中蓄积。SIRT 3是一种依赖于NAD+的线粒体脱乙酰酶，已被证明在控制参与能量代谢的许多酶的乙酰化状态中起关键作用。然而，SIRT 3在肥大相关脂质积聚发病机制中的作用仍不清楚。在这项研究中，肥厚相关的脂质积累进行了研究，使用小鼠心肌肥厚模型诱导的横向主动脉缩窄（TAC）。我们发现小鼠在TAC后六周发生心力衰竭。此外，在肥大的心脏中观察到异常的脂质积聚和棕榈酸氧化速率降低，这些变化在SIRT 3-KO小鼠中尤其显著。我们还证明了SIRT 3的短形式在野生型（WT）肥厚心脏中下调，并且这种变化伴随着长链酰基CoA脱氢酶（LCAD）的乙酰化水平更高，这是参与脂肪酸氧化的关键酶。此外，SIRT 3可能通过LCAD的脱乙酰化在减弱心脏中的脂质积累中发挥重要作用。
Cardiac hypertrophy is an adaptive response to pressure, volume stress, and loss of contractile mass from prior infarction. Metabolic changes in cardiac hypertrophy include suppression of fatty acid oxidation and enhancement of glucose utilization, which could result in lipid accumulation in the heart. SIRT3, a mitochondrial NAD+-dependent deacetylase, has been demonstrated to play a crucial role in controlling the acetylation status of many enzymes participating in energy metabolism. However, the role of SIRT3 in the pathogenesis of hypertrophy-related lipid accumulation remains unclear. In this study, hypertrophy-related lipid accumulation was investigated using a mouse cardiac hypertrophy model induced by transverse aortic constriction (TAC). We showed that mice developed heart failure six weeks after TAC. Furthermore, abnormal lipid accumulation and decreased palmitate oxidation rates were observed in the hypertrophic hearts, and these changes were particularly significant in SIRT3-KO mice. We also demonstrated that the short form of SIRT3 was downregulated in wild-type (WT) hypertrophic hearts and that this change was accompanied by a higher acetylation level of long-chain acyl CoA dehydrogenase (LCAD), which is a key enzyme participating in fatty acid oxidation. In addition, SIRT3 may play an essential role in attenuating lipid accumulation in the heart through the deacetylation of LCAD.
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DOI：
10.1046/j.1440-1681.2002.03655.x
发表时间：
2002-04-01
影响因子：
2.9
作者：
Lehman, JJ;Kelly, DP
通讯作者：
Kelly, DP
影响因子：
2.8
作者：
HOOD, WP;RACKLEY, CE;ROLETT, EL
通讯作者：
ROLETT, EL
影响因子：
10.5
作者：
Lin, SJ;Ford, E;Guarente, L
通讯作者：
Guarente, L
影响因子：
--
作者：
LITWIN, SE;RAYA, TE;BRESSLER, R
通讯作者：
BRESSLER, R
影响因子：
4.8
作者：
Giralt, Albert;Hondares, Elayne;Villarroya, Francesc
通讯作者：
Villarroya, Francesc