Science:生物钟基因和进食时间控制肝脏代谢节律
创作:mildbreeze 审核:mildbreeze 08月02日
  • 在成年小鼠中,敲除肝细胞中的核心生物钟调控因子REV-ERBα和β,可破坏一部分肝脏基因的节律性表达,主要涉及昼夜节律、激素分泌和脂质代谢;
  • 肝脏中的脂质新生等多种脂质代谢相关基因的节律性表达振幅增强,提示生物钟基因对于这些基因的波动有缓冲作用;
  • 在肝细胞中敲除REV-ERBα和β,还会影响肝细胞以外的其它肝脏细胞(血管内皮细胞和肝巨噬细胞等)的节律性转录组和代谢组;
  • 进食时间对多种肝脏细胞的节律性有塑造作用。
主编推荐语
mildbreeze
肝脏是机体代谢的中枢器官,Science发表的一项新研究发现,肝细胞中的关键生物钟调控因子REV-ERBα和β不仅影响肝细胞自身的基因表达和代谢节律,还能影响其它类型的肝脏细胞的生物钟,此外,进食时间对肝脏细胞的节律性也有很强的塑造作用。
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Science [IF:41.845]

The hepatocyte clock and feeding control chronophysiology of multiple liver cell types

肝细胞时钟和进食控制多种肝脏细胞类型的时间生理学

10.1126/science.aba8984

07-31, Article

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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. Here we show that deletion of core clock components REV-ERBα and β in adult mouse hepatocytes disrupted diurnal rhythms of a subset of liver genes and altered the diurnal rhythm of de novo lipogenesis. Liver function is also influenced by non-hepatocytic cells, and the loss of hepatocyte REV-ERBs remodeled the rhythmic transcriptomes and metabolomes of multiple cell types within the liver. Finally, alteration of food availability demonstrated 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.

First Authors:
Dongyin Guan

Correspondence Authors:
Mitchell A Lazar

All Authors:
Dongyin Guan,Ying Xiong,Trang Minh Trinh,Yang Xiao,Wenxiang Hu,Chunjie Jiang,Pieterjan Dierickx,Cholsoon Jang,Joshua D Rabinowitz,Mitchell A Lazar

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