Interdisciplinary Department of Medicine, University of Bari School of Medicine, Piazza G. Cesare, 11, 70124, Bari, Italy.
J Mol Med (Berl). 2019 Jun;97(6):741-759. doi: 10.1007/s00109-019-01780-2. Epub 2019 Apr 5.
Over the last decades, a better knowledge of the molecular machinery supervising the regulation of circadian clocks has been achieved, and numerous findings have helped in unravelling the outstanding significance of the molecular clock for the proper regulation of our physiologic and metabolic homeostasis. Non-alcoholic fatty liver disease (NAFLD) is currently considered as one of the emerging liver pathologies in the Western countries due to the modification of eating habits and lifestyle. Although NAFLD is considered a pretty benign condition, it can progress towards non-alcoholic steatohepatitis (NASH) and eventually hepatocellular carcinoma (HCC). The pathogenic mechanisms involved in NAFLD development are complex, since this disease is a multifactorial condition. Major metabolic deregulations along with a genetic background are believed to take part in this process. In this light, the aim of this review is to give a comprehensive description of how our circadian machinery is regulated and to describe to what extent our internal clock is involved in the regulation of hormonal and metabolic homeostasis, and by extension in the development and progression of NAFLD/NASH and eventually in the onset of HCC.
在过去的几十年中，人们对调节生物钟的分子机制有了更深入的了解，大量的研究结果有助于揭示生物钟对调节我们的生理和代谢平衡的重要意义。由于饮食习惯和生活方式的改变，非酒精性脂肪性肝病 (NAFLD) 目前被认为是西方国家新兴的肝脏疾病之一。尽管 NAFLD 被认为是一种良性疾病，但它可能会发展为非酒精性脂肪性肝炎 (NASH)，最终发展为肝细胞癌 (HCC)。NAFLD 发展的发病机制很复杂，因为这种疾病是一种多因素的疾病。主要的代谢紊乱和遗传背景被认为参与了这一过程。有鉴于此，本综述的目的是全面描述我们的生物钟是如何被调节的，并描述我们的内部时钟在多大程度上参与了激素和代谢平衡的调节，以及在 NAFLD/NASH 的发展和进展中，最终在 HCC 的发生中发挥作用。
