Short-term high salt intake impairs hepatic mitochondrial bioenergetics and biosynthesis in SIRT3 knockout mice
Short-term high salt intake impairs hepatic mitochondrial bioenergetics and biosynthesis in SIRT3 knockout mice
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短期高盐摄入会损害 SIRT3 敲除小鼠的肝线粒体生物能学和生物合成
DOI：
10.1080/10715762.2019.1580499
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发表时间：
2019-04
影响因子：
3.3
通讯作者：
Shi Dongyun
中科院分区：
文献类型：
--
作者：
Jiang Lihan;Chen Qinghua;Wu Meiling;Ji Tingting;Liu Shanlin;Zhu Fengge;Shi Dongyun
摘要高盐摄入(HS)是许多代谢性疾病发生的重要因素。肝脏是人体的代谢中心。然而，短期HS对肝脏线粒体的影响及其机制尚不清楚。在这项研究中，我们研究了短期HS对肝脏线粒体功能的影响。我们发现HS降低了Sirtuin3(SIRT3)的蛋白水平，增加了小鼠肝脏中的蛋白质甲基化。摄入HS会降低ATP产量、线粒体转录因子A(TFAM)和复合体I水平。SIRT3基因敲除(SKO)小鼠与HS处理的野生型小鼠表现出类似的结果，但羰化程度和ATP还原程度较小。我们的研究表明，短期HS导致肝脏氧化状态增强，线粒体生物合成和生物能量学受损。HS处理的小鼠仍可通过代偿性激活腺苷5‘-单磷酸活化蛋白激酶(AMPK)来维持肝脏葡萄糖稳态。然而，在HS处理的SKO小鼠中，AMPK没有被激活，相反，糖原合成酶活性增加，导致糖原积累异常增加。本研究提供了短期摄入HS可导致早期肝脏代谢改变的证据，强调了控制盐摄入量的重要性，特别是在SIRT3缺陷患者。强调高盐摄入量下调SIRT3蛋白水平并增加氧化。高盐摄入通过AMP依赖途径激活AMPK。高盐摄入会损害能量新陈代谢。高盐结合SIRT3基因敲除导致糖原积聚。
Abstract High salt intake (HS) is an important factor in the development of many metabolic diseases. The liver is the metabolic center in the body. However, the effect of short-term HS on the liver mitochondria and its mechanism are still unclear. In this study, we investigated the effects of short-term HS on liver mitochondrial function. We found that HS reduced Sirtuin3 (SIRT3) protein level, increasing protein carbonylation in mice liver. HS intake decreased ATP production, mitochondrial transcription factor A (TFAM), and complex I level. SIRT3 knockout (SKO) mice exhibited similar results with HS-treated wild-type mice but with a less extent of carbonylation and ATP reduction. Our study shows that short-term HS led to increased hepatic oxidative state, impaired mitochondrial biosynthesis, and bioenergetics. HS-treated mice could still maintain hepatic glucose homeostasis by compensatory activation of Adenosine 5′-monophosphate-activated protein kinase (AMPK). However, in HS-treated SKO mice, AMPK was not activated, instead, the glycogen synthase activity increased, which caused an exceptionally increased glycogen accumulation. This study provides evidence that short-term HS intake could cause the early hepatic metabolic changes, highlighting the importance of controlling salt intake especially in those patients with defects in SIRT3. Highlights High salt intake down-regulates SIRT3 protein level and increases oxidation. High salt intake activates AMPK via AMP-dependent pathway. High salt intake impairs energy metabolism. High salt combined with SIRT3 knockout results in glycogen accumulation.
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AMP激活的蛋白激酶对ULK1（HATG1）的磷酸化将能量传感连接到线粒体。
DOI：
10.1126/science.1196371
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Egan DF;Shackelford DB;Mihaylova MM;Gelino S;Kohnz RA;Mair W;Vasquez DS;Joshi A;Gwinn DM;Taylor R;Asara JM;Fitzpatrick J;Dillin A;Viollet B;Kundu M;Hansen M;Shaw RJ
通讯作者：
Shaw RJ
影响因子：
4
作者：
Brandauer J;Andersen MA;Kellezi H;Risis S;Frøsig C;Vienberg SG;Treebak JT
通讯作者：
Treebak JT
影响因子：
7.4
作者：
Dodson, Matthew;Darley-Usmar, Victor;Zhang, Jianhua
通讯作者：
Zhang, Jianhua
AMP 激活蛋白激酶 (AMPK) 通过调节脂肪组织中的产热来调节能量代谢
影响因子：
4
作者：
Wu L;Zhang L;Li B;Jiang H;Duan Y;Xie Z;Shuai L;Li J;Li J
通讯作者：
Li J
影响因子：
14.8
作者：
通讯作者：
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