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

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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.