Chrościcki Piotr, Usarek Michał, Bryla Jadwiga
Zakład Regulacji Metabolizmu, Instytut Biochemii, Wydział Biologii, Uniwersytet Warszawski, Warszawa.
Postepy Hig Med Dosw (Online). 2013 Jun 20;67:569-83. doi: 10.5604/17322693.1053906.
The mechanism of the biological clock is based on a rhythmic expression of clock genes and clock-controlled genes. As a result of their transcripto-translational associations, endogenous rhythms in the synthesis of key proteins of various physiological and metabolic processes are created. The major timekeeping mechanism for these rhythms exists in the central nervous system. The master circadian clock, localized in suprachiasmatic nucleus (SCN), regulates multiple metabolic pathways, while feeding behavior and metabolite availability can in turn regulate the circadian clock. It is also suggested that in the brain there is a food entrainable oscillator (FEO) or oscillators, resulting in activation of both food anticipatory activity and hormone secretion that control digestion processes. Moreover, most cells and tissues express autonomous clocks. Maintenance of the glucose homeostasis is particularly important for the proper function of the body, as this sugar is the main source of energy for the brain, retina, erythrocytes and skeletal muscles. Thus, glucose production and utilization are synchronized in time. The hypothalamic excited orexin neurons control energy balance of organism and modulate the glucose production and utilization. Deficiency of orexin action results in narcolepsy and weight gain, whereas glucose and amino acids can affect activity of the orexin cells. Large-scale genetic studies in rodents and humans provide evidence for the involvement of disrupted clock gene expression rhythms in the pathogenesis of obesity and type 2 diabetes. In general, the current lifestyle of the developed modern societies disturbs the action of biological clock.
生物钟的机制基于生物钟基因和生物钟控制基因的节律性表达。由于它们的转录-翻译关联,各种生理和代谢过程关键蛋白质合成中的内源性节律得以产生。这些节律的主要计时机制存在于中枢神经系统中。位于视交叉上核(SCN)的主昼夜节律时钟调节多种代谢途径,而进食行为和代谢物可用性反过来又可以调节昼夜节律时钟。也有人提出,大脑中存在一个或多个食物可调节振荡器(FEO),导致控制消化过程的食物预期活动和激素分泌均被激活。此外,大多数细胞和组织都表达自主时钟。维持葡萄糖稳态对身体的正常功能尤为重要,因为这种糖是大脑、视网膜、红细胞和骨骼肌的主要能量来源。因此,葡萄糖的产生和利用在时间上是同步的。下丘脑兴奋的食欲素神经元控制机体的能量平衡,并调节葡萄糖的产生和利用。食欲素作用缺乏会导致发作性睡病和体重增加,而葡萄糖和氨基酸会影响食欲素细胞的活性。对啮齿动物和人类的大规模基因研究为生物钟基因表达节律紊乱参与肥胖症和2型糖尿病的发病机制提供了证据。一般来说,现代发达社会目前的生活方式扰乱了生物钟的作用。