Hepatocytes are the main workers in the hepatic factory, managing metabolism of nutrients and xenobiotics, production and recycling of proteins, and glucose and lipid homeostasis. Division of labor between hepatocytes is critical to coordinate complex complementary or opposing multistep processes, similar to distributed tasks at an assembly line. This so-called metabolic zonation has both spatial and temporal components. Spatial distribution of metabolic function in hepatocytes of different lobular zones is necessary to perform complex sequential multistep metabolic processes and to assign metabolic tasks to the right environment. Moreover, temporal control of metabolic processes is critical to align required metabolic processes to the feeding and fasting cycles. Disruption of this complex spatiotemporal hepatic organization impairs key metabolic processes with both local and systemic consequences. Many metabolic diseases, such as nonalcoholic steatohepatitis and diabetes, are associated with impaired metabolic liver zonation. Recent technological advances shed new light on the spatiotemporal gene expression networks controlling liver function and how their deregulation may be involved in a large variety of diseases. We summarize the current knowledge about spatiotemporal metabolic liver zonation and consequences on liver pathobiology.

中文翻译：

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肝脏时空代谢分区及其对病理生理学的影响


肝细胞是肝脏工厂的主要工人，负责管理营养物质和外源物质的代谢、蛋白质的生产和回收以及葡萄糖和脂质的稳态。肝细胞之间的分工对于协调复杂的互补或相反的多步骤过程至关重要，类似于装配线上的分布式任务。这种所谓的代谢分区具有空间和时间两方面的成分。不同小叶区肝细胞代谢功能的空间分布对于执行复杂的连续多步代谢过程并将代谢任务分配给正确的环境是必要的。此外，代谢过程的时间控制对于使所需的代谢过程与进食和禁食周期保持一致至关重要。这种复杂的时空肝脏组织的破坏会损害关键的代谢过程，从而产生局部和全身的后果。许多代谢性疾病，例如非酒精性脂肪性肝炎和糖尿病，与代谢性肝分区受损有关。最近的技术进步为控制肝功能的时空基因表达网络以及它们的失调如何参与多种疾病提供了新的线索。我们总结了当前关于肝脏时空代谢分区及其对肝脏病理学影响的知识。