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

Science. 2020 Sep 11;369(6509):1388-1394. doi: 10.1126/science.aba8984. Epub 2020 Jul 30.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication
  • Circadian Clocks / genetics*
  • Circadian Rhythm / genetics*
  • Feeding Behavior*
  • Gene Deletion
  • Gene Expression Regulation*
  • Hepatocytes / physiology*
  • Liver / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / genetics
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Repressor Proteins / genetics


  • Nr1d1 protein, mouse
  • Nr1d2 protein, mouse
  • Nuclear Receptor Subfamily 1, Group D, Member 1
  • Receptors, Cytoplasmic and Nuclear
  • Repressor Proteins