Ando Hitoshi, Takamura Toshinari, Matsuzawa-Nagata Naoto, Shima Kosuke R, Nakamura Seiji, Kumazaki Masafumi, Kurita Seiichiro, Misu Hirofumi, Togawa Naoyuki, Fukushima Tatsunobu, Fujimura Akio, Kaneko Shuichi
Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641, Japan.
Biochem Biophys Res Commun. 2009 Mar 13;380(3):684-8. doi: 10.1016/j.bbrc.2009.01.150. Epub 2009 Jan 29.
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.
最近的研究已将代谢性疾病，如代谢综合征和非酒精性脂肪性肝病，与生物钟联系起来。然而，这种代谢变化本身是否会影响生物钟仍存在争议。为了解决这个问题，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）饮食小鼠模型肝脏中生物钟基因的每日mRNA表达谱。喂食致动脉粥样硬化饮食5周的C57BL/6J小鼠出现了高胆固醇血症、氧化应激和NASH。DNA芯片分析显示，致动脉粥样硬化饮食对与线粒体能量产生、氧化还原调节以及碳水化合物和脂质代谢相关的广泛基因的mRNA表达有很大影响。然而，肝脏中生物钟基因的节律性mRNA表达保持完整。大多数昼夜节律表达的基因也表现出24小时的节律性。这些发现表明生物钟能够抵御诸如NASH这样的代谢紊乱。
