Second-hand smoke stimulates lipid accumulation in the liver by modulating AMPK and SREBP-1.
Second-hand smoke stimulates lipid accumulation in the liver by modulating AMPK and SREBP-1.
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DOI：
10.1016/j.jhep.2009.03.026
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发表时间：
2009-09
影响因子：
25.7
通讯作者：
Martins-Green M
中科院分区：
文献类型：
--
作者：
Yuan H;Shyy JY;Martins-Green M
脂肪变性是非酒精性脂肪性肝病（NAFLD）的第一阶段，其特征是肝细胞中脂质的积累，其潜在机制仍不清楚。我们的研究旨在调查香烟烟雾已知会改变循环脂质谱的假设，因此也可能有助于肝脏中脂质的积累。将小鼠和培养的肝细胞暴露于侧流全烟（SSW），“二手”烟的主要成分，并使用各种细胞和分子方法来研究香烟烟雾对脂质代谢的影响。SSW通过调节5′-AMP活化蛋白激酶（AMPK）和固醇反应元件结合蛋白-1（SREBP-1）的活性增加肝细胞中的脂质蓄积，这两种分子参与脂质合成。SSW引起AMPK的去磷酸化/失活，这有助于增加SREBP-1的活化。这些活性变化导致甘油三酯在肝细胞中蓄积。这些新的发现很重要，因为它们指出了吸烟的另一个危险因素，即，导致NAFLD。此外，我们的研究结果表明，AMPK和SREBP都是关键参与这些影响的烟雾点的潜在用途，这些分子作为目标的香烟烟雾诱导的代谢性疾病的治疗。
The underlying mechanisms of steatosis, the first stage of non-alcoholic fatty liver disease (NAFLD) that is characterized by the accumulation of lipids in hepatocytes, remain unclear. Our study aimed to investigate the hypothesis that cigarette smoke is known to change circulating lipid profiles and thus may also contribute to the accumulation of lipids in the liver. Mice and cultured hepatocytes were exposed to sidestream whole smoke (SSW), a major component of “second-hand” smoke and a variety of cellular and molecular approaches were used to study the effects of cigarette smoke on lipid metabolism. SSW increases lipid accumulation in hepatocytes by modulating the activity of 5′-AMP-activated protein kinase (AMPK) and sterol response element binding protein-1 (SREBP-1), two critical molecules involved in lipid synthesis. SSW causes dephosphorylation/ inactivation of AMPK, which contributes to increased activation of SREBP-1. These changes of activity lead to accumulation of triglycerides in hepatocytes. These novel findings are important because they point to another risk factor of smoking, i.e., that of contributing to NAFLD. In addition, our results showing that both AMPK and SREBP are critically involved in these effects of smoke point to the potential use of these molecules as targets for treatment of cigarette smoke-induced metabolic diseases.
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影响因子：
8.7
作者：
Hotta, K;Funahashi, T;Matsuzawa, Y
通讯作者：
Matsuzawa, Y
影响因子：
4
作者：
Fleming, I;Fisslthaler, B;Busse, R
通讯作者：
Busse, R
影响因子：
7.7
作者：
Foretz, M;Ancellin, N;Viollet, B
通讯作者：
Viollet, B
影响因子：
3.9
作者：
Barb, D.;Neuwirth, A.;Balk, S. P.
通讯作者：
Balk, S. P.
DOI：
10.1073/pnas.96.20.11041
发表时间：
1999-09-28
影响因子：
11.1
作者：
Brown, MS;Goldstein, JL
通讯作者：
Goldstein, JL