Kohsaka Akira, Laposky Aaron D, Ramsey Kathryn Moynihan, Estrada Carmela, Joshu Corinne, Kobayashi Yumiko, Turek Fred W, Bass Joseph
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA.
Cell Metab. 2007 Nov;6(5):414-21. doi: 10.1016/j.cmet.2007.09.006.
The circadian clock programs daily rhythms and coordinates multiple behavioral and physiological processes, including activity, sleep, feeding, and fuel homeostasis. Recent studies indicate that genetic alteration in the core molecular clock machinery can have pronounced effects on both peripheral and central metabolic regulatory signals. Many metabolic systems also cycle and may in turn affect function of clock genes and circadian systems. However, little is known about how alterations in energy balance affect the clock. Here we show that a high-fat diet in mice leads to changes in the period of the locomotor activity rhythm and alterations in the expression and cycling of canonical circadian clock genes, nuclear receptors that regulate clock transcription factors, and clock-controlled genes involved in fuel utilization in the hypothalamus, liver, and adipose tissue. These results indicate that consumption of a high-calorie diet alters the function of the mammalian circadian clock.
昼夜节律时钟调控日常节律，并协调多种行为和生理过程，包括活动、睡眠、进食以及能量稳态。最近的研究表明，核心分子时钟机制的基因改变可对外周和中枢代谢调节信号产生显著影响。许多代谢系统也呈周期性变化，进而可能影响时钟基因和昼夜节律系统的功能。然而，关于能量平衡的改变如何影响生物钟，我们知之甚少。在此我们表明，小鼠的高脂饮食会导致运动活动节律周期的变化，以及下丘脑、肝脏和脂肪组织中经典昼夜节律时钟基因、调节时钟转录因子的核受体以及参与燃料利用的时钟控制基因的表达和周期性变化。这些结果表明，高热量饮食的摄入会改变哺乳动物昼夜节律时钟的功能。
