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
Date Published2020 Sep 11
KeywordsAnimals, Cell Communication, Circadian Clocks, Circadian Rhythm, Feeding Behavior, Gene Deletion, Gene Expression Regulation, Hepatocytes, Liver, Mice, Mice, Inbred C57BL, Mice, Knockout, Nuclear Receptor Subfamily 1, Group D, Member 1, Receptors, Cytoplasmic and Nuclear, Repressor Proteins

<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>

Alternate JournalScience
PubMed ID32732282
PubMed Central IDPMC7849028
Grant ListF32 DK116519 / DK / NIDDK NIH HHS / United States
P30 DK019525 / DK / NIDDK NIH HHS / United States
R01 DK045586 / DK / NIDDK NIH HHS / United States