Nutritional Genomics of Cardiovascular Disease and Obesity, IMDEA Food CEI UAM + CSIC, 28049 Madrid, Spain.
Int J Mol Sci. 2016 Feb 26;17(3):299. doi: 10.3390/ijms17030299.
Even though the rhythmic oscillations of life have long been known, the precise molecular mechanisms of the biological clock are only recently being explored. Circadian rhythms are found in virtually all organisms and affect our lives. Thus, it is not surprising that the correct running of this clock is essential for cellular functions and health. The circadian system is composed of an intricate network of genes interwined in an intrincated transcriptional/translational feedback loop. The precise oscillation of this clock is controlled by the circadian genes that, in turn, regulate the circadian oscillations of many cellular pathways. Consequently, variations in these genes have been associated with human diseases and metabolic disorders. From a nutrigenetics point of view, some of these variations modify the individual response to the diet and interact with nutrients to modulate such response. This circadian feedback loop is also epigenetically modulated. Among the epigenetic mechanisms that control circadian rhythms, microRNAs are the least studied ones. In this paper, we review the variants of circadian-related genes associated to human disease and nutritional response and discuss the current knowledge about circadian microRNAs. Accumulated evidence on the genetics and epigenetics of the circadian system points to important implications of chronotherapy in the clinical practice, not only in terms of pharmacotherapy, but also for dietary interventions. However, interventional studies (especially nutritional trials) that include chronotherapy are scarce. Given the importance of chronobiology in human health such studies are warranted in the near future.
尽管生命的节奏性波动早已为人所知，但生物钟的精确分子机制直到最近才被探索。昼夜节律几乎存在于所有生物体中，并影响着我们的生活。因此，这个时钟的正确运行对细胞功能和健康至关重要也就不足为奇了。生物钟系统由一个错综复杂的基因网络组成，这些基因交织在一个复杂的转录/翻译反馈环中。这个时钟的精确波动由生物钟基因控制，而生物钟基因又调节着许多细胞途径的昼夜节律波动。因此，这些基因的变异与人类疾病和代谢紊乱有关。从营养遗传学的角度来看，这些变异中的一些会改变个体对饮食的反应，并与营养素相互作用来调节这种反应。这个生物钟反馈环也受到表观遗传的调节。在控制昼夜节律的表观遗传机制中，microRNAs 是研究最少的一种。在本文中，我们回顾了与人类疾病和营养反应相关的生物钟基因的变异，并讨论了关于昼夜节律 microRNAs 的现有知识。生物钟系统的遗传学和表观遗传学的累积证据表明，时间治疗在临床实践中的应用具有重要意义，不仅在药物治疗方面，而且在饮食干预方面也是如此。然而，包括时间治疗在内的干预性研究（特别是营养试验）却很少。鉴于生物钟生物学在人类健康中的重要性，在不久的将来，此类研究是有必要的。
