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

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

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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. We show that deletion of core clock components REV-ERBa and REV-ERBb 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.

Original languageEnglish (US)
Pages (from-to)1388-1395
Number of pages8
JournalScience
Volume369
Issue number6509
DOIs
StatePublished - Sep 2020

All Science Journal Classification (ASJC) codes

  • General

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