All living organisms including humans, experience changes in the light exposure generated by the Earth's rotation. In anticipation of this unavoidable geo-physical variability, and to generate an appropriate biochemical response, species of many phyla, including mammals have evolved a nearly 24-h endogenous timing device known as the circadian clock (CC), which is self-sustained, cell autonomous and is present in every cell type. At the heart of the ‘clock’ functioning resides the CC-oscillator, an elegantly designed transcriptional-translational feedback system. Notably, the core components of the CC-oscillator not only drive daily rhythmicity of their own synthesis, but also generate circadian phase-specific variability in the expression levels of thousands of target genes through transcriptional, post-transcriptional and post-translational mechanisms. Thereby, this ‘clock’-system provides proper chronological coordination in the functioning of cells, tissues and organs. The CC governs many physiologically critical functions. Among these functions, the key role of the CC in maintaining metabolic homeostasis deserves special emphasis. Indeed, the several features of the modern lifestyle (e.g. travel-induced jet lag, rotating shift work, energy-dense food) which, force disruption of circadian rhythms have recently emerged as a major driver to global health problems like obesity, cardiovascular disease and metabolic liver disease such as non-alcoholic fatty liver disease (NAFLD). Here we review, the CC-dependent pathways in different tissues which play critical roles in mediating several critical metabolic functions under physiological conditions and discuss their impact for the development of metabolic disease with a focus on the liver.

包括人类在内的所有生物都会经历地球自转产生的光照变化。预料到这种不可避免的地球物理变化，并产生适当的生化反应，许多门的物种，包括哺乳动物，已经进化出一种近 24 小时的内源性计时装置，称为生物钟 (CC)，它是自我维持的，细胞自主并存在于每种细胞类型中。“时钟”功能的核心是 CC 振荡器，这是一个设计精美的转录-翻译反馈系统。值得注意的是，CC 振荡器的核心组件不仅驱动其自身合成的日常节律性，而且还通过转录在数千个靶基因的表达水平上产生昼夜节律特异性变异，转录后和翻译后机制。因此，这个“时钟”系统在细胞、组织和器官的功能中提供了适当的时间协调。CC控制着许多生理上的关键功能。在这些功能中，CC 在维持代谢稳态中的关键作用值得特别强调。事实上，现代生活方式的几个特征（例如旅行引起的时差、轮班工作、能量密集的食物），迫使昼夜节律被打乱，最近已成为全球健康问题的主要驱动因素，如肥胖、心血管疾病和代谢性肝病，例如非酒精性脂肪肝（NAFLD）。在这里我们回顾一下，