The hepatocyte clock and food availability control gene expression and metabolism in nonhepatocytic cells in the liver. Keeping rhythm requires communication In mammals, daily cycles in physiology require the synchronized activity of circadian clocks in peripheral organs such as the liver, a hub of metabolism. Guan et al. generated mice with hepatocytes that lack two transcriptional repressors known to be essential for clock function. This experimental manipulation unexpectedly disrupted rhythmic gene expression and metabolism not only in hepatocytes but also in other liver cell types. Feeding behavior also coregulated circadian rhythms in multiple liver cell types. Cell-cell communication thus appears to be important in maintaining the robustness of peripheral circadian clocks. Science, this issue p. 1388 Most cells of the body contain molecular clocks, but the requirement of peripheral clocks for rhythmicity and their effects on physiology are not well understood. We show that deletion of core clock components REV-ERBα and REV-ERBβ in adult mouse hepatocytes disrupts diurnal rhythms of a subset of liver genes and alters the diurnal rhythm of de novo lipogenesis. Liver function is also influenced by nonhepatocytic cells, and the loss of hepatocyte REV-ERBs remodels the rhythmic transcriptomes and metabolomes of multiple cell types within the liver. Finally, alteration of food availability demonstrates the hierarchy of the cell-intrinsic hepatocyte clock mechanism and the feeding environment. Together, these studies reveal previously unsuspected roles of the hepatocyte clock in the physiological coordination of nutritional signals and cell-cell communication controlling rhythmic metabolism.

中文翻译：

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多种肝细胞类型的肝细胞时钟和摄食控制时间生理学

肝细胞时钟和食物供应控制肝脏非肝细胞的基因表达和代谢。保持节律需要交流 在哺乳动物中，生理学的日常周期需要外周器官的生物钟同步活动，例如肝脏，新陈代谢的枢纽。关等人。生成的小鼠肝细胞缺乏两种已知对时钟功能至关重要的转录抑制因子。这种实验操作出人意料地破坏了不仅在肝细胞中而且在其他肝细胞类型中的节律基因表达和代谢。进食行为还协同调节多种肝细胞类型的昼夜节律。因此，细胞间通讯对于维持外周生物钟的稳健性似乎很重要。科学，这个问题 p。1388 身体的大多数细胞都含有分子钟，但外周时钟对节律性的要求及其对生理的影响尚不清楚。我们表明，成年小鼠肝细胞中核心时钟成分 REV-ERBα 和 REV-ERBβ 的缺失会破坏一部分肝脏基因的昼夜节律，并改变从头脂肪生成的昼夜节律。肝功能也受非肝细胞的影响，肝细胞 REV-ERB 的缺失重塑了肝脏内多种细胞类型的节律性转录组和代谢组。最后，食物可用性的改变表明细胞内在肝细胞时钟机制和喂养环境的层次结构。一起，