The hepatic circadian clock is preserved in a lipid-induced mouse model of non-alcoholic steatohepatitis
The hepatic circadian clock is preserved in a lipid-induced mouse model of non-alcoholic steatohepatitis
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DOI：
10.1016/j.bbrc.2009.01.150
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发表时间：
2009-03-13
影响因子：
3.1
通讯作者：
Kaneko, Shuichi
中科院分区：
文献类型：
--
作者：
Ando, Hitoshi;Takamura, Toshinari;Kaneko, Shuichi
最近的研究表明，代谢综合征和非酒精性脂肪性肝病等代谢性疾病与生物钟有关。然而，这种代谢变化本身是否会影响生物钟仍然存在争议。为了解决这一问题，我们使用定制的高精度DNA芯片研究了非酒精性脂肪性肝炎(NASH)饮食小鼠肝脏时钟基因的每日mRNA表达谱。喂饲致动脉粥样硬化饲料5周的C57BL/6J小鼠出现高胆固醇血症、氧化应激和NASH。DNA芯片分析表明，致动脉粥样硬化的饮食对线粒体能量产生、氧化还原调节以及碳水化合物和脂肪代谢相关的一系列基因的mRNA表达有很大影响。然而，肝脏中时钟基因的节律性mRNA表达保持不变。大多数昼夜节律表达的基因也具有24小时节律性。这些发现表明，生物钟受到保护，不受像NASH这样的代谢紊乱的影响。(C)2009 Elsevier Inc.保留所有权利。
Recent studies have correlated metabolic diseases, such as metabolic syndrome and non-alcoholic fatty liver disease, with the circadian clock. However, whether such metabolic changes per se affect the circadian clock remains controversial. To address this, we investigated the daily mRNA expression profiles of clock genes in the liver of a dietary mouse model of non-alcoholic steatohepatitis (NASH) using a custom-made, high-precision DNA chip. C57BL/6J mice fed an atherogenic diet for 5 weeks developed hypercholesterolemia, oxidative stress, and NASH. DNA chip analyses revealed that the atherogenic diet had a great influence on the mRNA expression of a wide range of genes linked to mitochondrial energy production, redox regulation, and carbohydrate and lipid metabolism. However, the rhythmic mRNA expression of the clock genes in the liver remained intact. Most of the circadianly expressed genes also showed 24-h rhythmicity. These findings Suggest that the biological clock is protected against such a metabolic derangement as NASH. (C) 2009 Elsevier Inc. All rights reserved.