Melatonin alleviates lipopolysaccharide-induced hepatic SREBP-1c activation and lipid accumulation in mice
Melatonin alleviates lipopolysaccharide-induced hepatic SREBP-1c activation and lipid accumulation in mice
复制标题
褪黑素减轻脂多糖诱导的小鼠肝脏 SREBP-1c 激活和脂质积累
DOI：
10.1111/j.1600-079x.2011.00905.x
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发表时间：
2011-11-01
影响因子：
10.3
通讯作者：
Xu, De-Xiang
中科院分区：
文献类型：
--
作者：
Chen, Xi;Zhang, Cheng;Xu, De-Xiang
内毒素血症和非酒精性脂肪性肝病（NAFLD）之间的联系已在人类和啮齿类动物中得到证实。然而，内毒素诱发的NAFLD的分子机制仍然知之甚少。我们假设活性氧（ROS）介导脂多糖（LPS）诱导的肝脏脂质蓄积。褪黑激素是一种抗氧化剂。在本研究中，我们研究了褪黑激素对LPS诱导的肝脏脂质蓄积的影响。我们发现，一个单一剂量的LPS显着增加肝脏甘油三酯（TG）含量，并导致肝脏脂质蓄积的小鼠。进一步的分析发现，在LPS处理的小鼠中，肝固醇调节元件结合蛋白（SREBP）-1c被激活。与肝脏SREBP-1c激活一致，脂肪酸合成酶（FAS）和乙酰辅酶A羧化酶（ACC），两个SREBP-1c靶基因，在注射LPS的小鼠肝脏中显著上调。褪黑激素显著减弱LPS诱导的SREBP-1c激活和SREBP-1c靶基因的表达。此外，褪黑激素降低血清和肝脏甘油三酯（TG）含量，并防止LPS诱导的肝脏脂质积聚。综上所述，这些结果表明，ROS可能，至少部分，介导的LPS诱导的SREBP-1c激活和肝脏脂质积累。褪黑激素可用作防止内毒素诱发的NAFLD的药理学试剂。
A link between endotoxemia and nonalcoholic fatty liver disease (NAFLD) has been demonstrated in human and rodent animals. Nevertheless, the molecular mechanisms of endotoxin-evoked NAFLD remain poorly understood. We hypothesize that reactive oxygen species (ROS) mediate lipopolysaccharide (LPS)-evoked hepatic lipid accumulation. Melatonin is an antioxidant. In the present study, we investigated the effects of melatonin on LPS-induced hepatic lipid accumulation. We showed that a single dose of LPS significantly increased hepatic triglyceride (TG) contents and caused hepatic lipid accumulation in mice. Further analysis found that hepatic sterol regulatory element-binding protein (SREBP)-1c was activated in LPS-treated mice. In agreement with hepatic SREBP-1c activation, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), two SREBP-1c target genes, were significantly upregulated in liver of mice injected with LPS. Melatonin significantly attenuated LPS-induced SREBP-1c activation and the expression of SREBP-1c target genes. In addition, melatonin reduced serum and hepatic triglyceride (TG) content and prevented LPS-induced hepatic lipid accumulation. Taken together, these results suggest that ROS might be, at least partially, mediated in LPS-induced SREBP-1c activation and hepatic lipid accumulation. Melatonin may be useful as pharmacological agents to protect against endotoxin-evoked NAFLD.