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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE143528 | GEO | 2020/07/30

REPOSITORIES: GEO

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

Project description: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-ERB? and REV-ERB? 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.

| S-EPMC7849028 | biostudies-literature

The Hepatocyte Clock and Feeding Interdependently Control Chrono-Homeostasis of Multiple Liver Cell Types (RNA-seq)

Project description:Most cells in the body contain a cell autonomous molecular clock, but the requirement of peripheral clocks for circadian rhythmicity, and their effects on physiology, are not well understood. Here we show that deletion of core clock components REV-ERBa and b in adult mouse hepatocytes caused the loss of circadian rhythmicity of many liver genes, as expected, but also led to maintained and even gained rhythmicity of other genes without altering feeding behavior. The loss of REV-ERBs from hepatocytes leads to an exaggerated circadian rhythm of de novo lipogenesis and serum triglyceride levels. It is increasingly recognized that liver function is also influenced by non-hepatocytic cells, and remarkably the loss of REV-ERBs in hepatocytes remodeled the circadian transcriptomes of multiple cell types within the liver without altering their core clocks, indicating that hepatocytes communicated time signals to the non-hepatocytic cells. Finally, alteration of food availability, which is the dominant zeitgeber in the liver, demonstrated strong interdependence of the cell-autonomous hepatocyte clock mechanism and non-cell-autonomous environmental change. Together these studies reveal the interdependence of endogenous hepatocyte clocks and feeding entrainment on the regulation of circadian rhythms of multiple cell types in the liver.

2020-07-30 | GSE143524 | GEO