The central clock suffices to drive the majority of circulatory metabolic rhythms

Paul Petrus, Jacob G. Smith, Kevin B. Koronowski, Siwei Chen, Tomoki Sato, Carolina M. Greco, Thomas Mortimer, Patrick Simon Welz, Valentina M. Zinna, Kohei Shimaji, Marlene Cervantes, Daniela Punzo, Pierre Baldi, Pura Munoz-Canoves, Paolo Sassone-Corsi, Salvador Aznar Benitah

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Life on Earth anticipates recurring 24-hour environmental cycles via genetically encoded molecular clocks active in all mammalian organs. Communication between these clocks controls circadian homeostasis. Intertissue communication is mediated, in part, by temporal coordination of metabolism. Here, we characterize the extent to which clocks in different organs control systemic metabolic rhythms, an area that remains largely unexplored. We analyzed the metabolome of serum from mice with tissue-specific expression of the clock gene Bmal1. Having functional hepatic and muscle clocks can only drive a minority (13%) of systemic metabolic rhythms. Conversely, limiting Bmal1 expression to the central pacemaker in the brain restores rhythms to 57% of circulatory metabolites. Rhythmic feeding imposed on clockless mice resulted in a similar rescue, indicating that the central clock mainly regulates metabolic rhythms via behavior. These findings explicate the circadian communication between tissues and highlight the importance of the central clock in governing those signals.

Original languageEnglish (US)
Article numbereabo2896
JournalScience Advances
Volume8
Issue number26
DOIs
StatePublished - Jul 2022
Externally publishedYes

ASJC Scopus subject areas

  • General

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