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

TitleThe hepatocyte clock and feeding control chronophysiology of multiple liver cell types.
Publication TypeJournal Article
Year of Publication2020
AuthorsGuan, D, Xiong, Y, Trinh, TMinh, Xiao, Y, Hu, W, Jiang, C, Dierickx, P, Jang, C, Rabinowitz, JD, Lazar, MA
JournalScience
Volume369
Issue6509
Pagination1388-1394
Date Published2020 Sep 11
ISSN1095-9203
Abstract

<p>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.</p>

DOI10.1126/science.aba8984
Alternate JournalScience
PubMed ID32732282