ステロイド合成細胞のクロノメタボリズム：細胞代謝と生理の概日時計による制御機構

在我们的星球上，地球围绕太阳的自转带来了一个24小时的明暗循环，塑造了所有生物的生活方式。在预期和适应这些可预测的周期性光信号，大多数生物体已经进化到表现出昼夜动态行为和生理节律，简称为昼夜节律。在具有完整身体系统的哺乳动物中，昼夜节律是普遍存在的，不仅存在于视交叉上核（SCN;也被称为昼夜节律钟的中央起搏器），而且存在于各种外周组织（被认为是外周昼夜节律振荡器）中。SCN和外周组织中生物钟的分子机制由保守的互锁转录-翻译反馈环组成，该反馈环涉及产生内源性生物钟振荡所需的多个时钟基因及其蛋白质产物。我们检查了类固醇合成器官如卵巢和肾上腺的时间代谢。在研究过程中，我们注意到类固醇代谢与许多其他代谢相互关联，而肝脏是大多数代谢的关键器官。为了理解时间代谢的整个背景，我们研究了肝脏，我们开始研究基本的能量来源，糖原。我们使用周期基因缺陷小鼠和野生型小鼠研究了肝时钟和食物对肝糖原储存的影响，发现糖原储存受到生物钟的强烈调节。我们现在正在研究葡萄糖和类固醇代谢的相互联系。

On our planet, the earth’s rotation around the sun brings about a 24-h light-dark cycle that shapes the lifestyle of all living organisms. In anticipation of and adaption to those predictable cyclic light signals, most organisms have evolved to exhibit diurnal dynamic behavioral and physiological rhythms, known simply as circadian rhythms. In mammals with an intact body system, circadian rhythms are ubiquitous, residing not only in the suprachiasmatic nucleus (SCN; also known as the central pacemaker of the circadian clock) but also in various peripheral tissues (regarded as peripheral circadian oscillator). The molecular machinery underlying circadian clocks in the SCN and peripheral tissues is composed of a conservative interlocked transcriptional-translational feed-back loop involving multiple clock genes and their protein products that are required for generating endogenous circadian oscillations. We examined chronometaolism in steroid synthetic organs such as ovary and adrenal glands. During the course of study, we noticed that steroid metabolism interlocks with many other metabolisms, and liver is a key organ of most metabolisms. To understand the whole context of chronometabolism, we choosed liver, and we began a study of fundamental energy source, glycogen. We investigated the effect of hepatic clock and food on hepatic glycogen storage using Period genes deficient mice and wild type mice, and found that glycogen storage was strongly regulated by the circadian clock. We are now investigating the interlocks of glucose and steroid metabolisms.