生物钟基因在非酒精性脂肪性肝病发生发展中的作用

生物钟是生物体为了适应昼夜交替引起的光照、温度等变化而在漫长的进化过程中形成的内在变化节律。人类生物钟在分子水平上由多个生物钟基因精确调控;在解剖水平上由中枢生物钟和外周生物钟分级调控。近年来研究发现,生物钟基因可通过对下游钟控基因的调控参与细胞内的脂质代谢,并且有研究证实生物钟基因紊乱可导致与非酒精性脂肪性肝病(NAFLD)发病密切相关的脂代谢异常、氧化应激、胰岛素抵抗、糖皮质激素及炎症因子分泌异常等,生物钟基因的紊乱可增加临床上脂肪肝的易感性,这可以作为生物钟基因和NAFLD相关性研究的桥梁。现阶段NAFLD的发病机制尚不明确,综述了近年来国内外对生物钟基因及NAFLD的研究,旨在为进一步明确NAFLD的发病机制提供理论基础。

Role of circadian clock genes in the development and progression of nonalcoholic fatty liver disease

Circadian clock is an inherent biological rhythm of organism which forms in the long process of evolution to adapt to the changes in light and temperature due to day-night alternation.Circadian clock in humans is accurately regulated by various circadian clock genes at the molecular level and are hierarchically regulated by the central clock and the peripheral clock at the anatomical level.Recent studies have found that circadian clock genes can participate in intracellular lipid metabolism by regulating downstream clock-controlled genes,and the disorder of circadian clock genes can result in abnormal lipid metabolism,oxidative stress,insulin resistance,and abnormal secretion of glucocorticoids and inflammatory factors,which are closely associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD).The disorder of circadian clock genes can also increase the susceptibility to fatty liver disease and thus acts as a bridge that connects circadian clock genes and NAFLD.The pathogenesis of NAFLD remains unclear at present,and therefore,this article summarizes the recent studies on the association between circadian clock genes and NAFLD,so as to provide a theoretical basis for further clarifying the pathogenesis of NAFLD.