α-Terpineol induces fatty liver in mice mediated by the AMP-activated kinase and sterol response element binding protein pathway
α-Terpineol induces fatty liver in mice mediated by the AMP-activated kinase and sterol response element binding protein pathway
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DOI：
10.1016/j.fct.2012.12.025
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发表时间：
2013-05-01
影响因子：
4.3
通讯作者：
Lee, Byung-Hoon
中科院分区：
文献类型：
--
作者：
Choi, You-Jin;Sim, Woo-Cheol;Lee, Byung-Hoon
草药在疾病预防和治疗中的使用在世界范围内迅速增长，但没有仔细考虑安全问题。 α-松油醇是互叶白千层、鼠尾草和红花的单萜醇成分，广泛用作食品中的香料和精油。本研究表明，α-萜品醇通过 AMP 激活蛋白激酶 (AMPK)-mTOR-甾醇调节元件结合蛋白-1 (SREBP-1) 途径诱导脂肪肝。 α-萜品醇处理的肝细胞显着增加中性脂质积累。 α-松油醇抑制 AMPK 磷酸化，并增加 p70S6 激酶 (p70S6K) 磷酸化和 SREBP-1 激活。它还增加了用 LXRE-tk-Luc 和 SRE-tk-Luc 转染的细胞中的荧光素酶活性。通过与雷帕霉素共同治疗或与显性失活 p70S6K 共转染来抑制 mTOR 信号传导，完全阻断了 α-萜品醇的作用。给小鼠口服 α-萜品醇 2 周，导致肝脏中 AMPK 磷酸化减少，SREBP-1 激活增加，随后肝脏脂质积累。相反，雷帕霉素联合治疗可逆转 α-萜品醇诱导的 SREBP-1 激活和小鼠脂肪肝。这些数据提供了 α-萜品醇导致脂肪肝的证据，这是一种由 AMPK/mTOR/SREBP-1 通路介导的效应。 0 2013 Elsevier Ltd. 保留所有权利。
The use of herbal medicines in disease prevention and treatment is growing rapidly worldwide, without careful consideration of safety issues. alpha-Terpineol is a monoterpene alcoholic component of Melaleuca alternifolia, Salvia officinalis and Carthamus tinctorius that is used widely as a flavor and essential oil in food. The present study showed that alpha-terpineol induces fatty liver via the AMP-activated protein kinase (AMPK)-mTOR-sterol regulatory element-binding protein-1 (SREBP-1) pathway. alpha-Terpineol-treated hepatocytes had significantly increased neutral lipid accumulation. alpha-Terpineol suppressed AMPK phosphorylation, and increased p70S6 kinase (p70S6K) phosphorylation and SREBP-1 activation. It also increased luciferase activity in cells transfected with LXRE-tk-Luc and SRE-tk-Luc. Inhibition of mTOR signaling by co-treatment with rapamycin or co-transfection with dominant negative p70S6K blocked completely the effects of alpha-terpineol. alpha-Terpineol oral administration to mice for 2 weeks led to decreased AMPK phosphorylation and increased SREBP-1 activation in the liver, followed by hepatic lipid accumulation. Conversely, rapamycin co-treatment reversed alpha-terpineol-induced SREBP-1 activation and fatty liver in mice. These data provide evidence that alpha-terpineol causes fatty liver, an effect mediated by the AMPK/mTOR/SREBP-1 pathway. 0 2013 Elsevier Ltd. All rights reserved.