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肝细胞节律和进食调控多种类型肝细胞的时间生理学
作者:小柯机器人 发布时间:2020/8/2 23:24:19

美国宾夕法尼亚大学Mitchell A. Lazar及其研究小组发现,肝细胞节律和进食调控多种类型肝细胞的时间生理学。该项研究成果发表在2020年7月31日出版的《科学》杂志上。

研究人员发现成年小鼠肝细胞中核心时钟组分REV-ERBα和β的缺失破坏了部分肝基因的昼夜节律,并改变了新生脂肪形成的昼夜节律。肝功能还受到非肝细胞的影响,并且肝细胞REV-ERB的丢失重塑了肝内多种类型细胞的转录组和代谢组节律。

最后,食物供应量的变化印证了细胞内源性肝细胞时钟机制和摄食环境的等级。总之,这些研究揭示了肝细胞时钟在营养信号的生理协调和控制节律性代谢细胞间通讯中未知的作用。

研究人员表示,人体的大多数细胞都含有分子时钟,但是尚不清楚节律对环境时钟的需求及其对生理的影响。

附:英文原文

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

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

Issue&Volume: 2020/07/30

Abstract: Abstract 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.

DOI: 10.1126/science.aba8984

Source: https://science.sciencemag.org/content/early/2020/07/29/science.aba8984

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037