The liver-clock coordinates rhythmicity of peripheral tissues in response to feeding

Gal Manella, Elizabeth Sabath, Rona Aviram, Vaishnavi Dandavate, Saar Ezagouri, Marina Golik, Yaarit Adamovich, Gad Asher

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

The mammalian circadian system consists of a central clock in the brain that synchronizes clocks in the peripheral tissues. Although the hierarchy between central and peripheral clocks is established, little is known regarding the specificity and functional organization of peripheral clocks. Here, we employ altered feeding paradigms in conjunction with liver-clock mutant mice to map disparities and interactions between peripheral rhythms. We find that peripheral clocks largely differ in their responses to feeding time. Disruption of the liver-clock, despite its prominent role in nutrient processing, does not affect the rhythmicity of clocks in other peripheral tissues. Yet, unexpectedly, liver-clock disruption strongly modulates the transcriptional rhythmicity of peripheral tissues, primarily on daytime feeding. Concomitantly, liver-clock mutant mice exhibit impaired glucose and lipid homeostasis, which are aggravated by daytime feeding. Overall, our findings suggest that, upon nutrient challenge, the liver-clock buffers the effect of feeding-related signals on rhythmicity of peripheral tissues, irrespective of their clocks.

Original languageEnglish
Pages (from-to)829-842
Number of pages14
JournalNature Metabolism
Volume3
Issue number6
DOIs
StatePublished - Jun 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.

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