The hepatocyte clock and feeding control chronophysiology of multiple liver cell types. Author Dongyin Guan, Ying Xiong, Trang Trinh, Yang Xiao, Wenxiang Hu, Chunjie Jiang, Pieterjan Dierickx, Cholsoon Jang, Joshua Rabinowitz, Mitchell Lazar Publication Year 2020 Type Journal Article 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-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. Keywords Repressor Proteins, Animals, Mice, Gene Expression Regulation, Gene Deletion, Receptors, Cytoplasmic and Nuclear, Cell Communication, Mice, Inbred C57BL, Mice, Knockout, Hepatocytes, Feeding Behavior, Circadian Clocks, Liver, Circadian Rhythm, Nuclear Receptor Subfamily 1, Group D, Member 1 Journal Science Volume 369 Issue 6509 Pages 1388-1394 Date Published 2020 Sep 11 ISSN Number 1095-9203 DOI 10.1126/science.aba8984 Alternate Journal Science PMCID PMC7849028 PMID 32732282 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML