Integration of feeding behavior by the liver circadian clock reveals network dependency of metabolic rhythms

Carolina M. Greco, Kevin B. Koronowski, Jacob G. Smith, Jiejun Shi, Paolo Kunderfranco, Roberta Carriero, Siwei Chen, Muntaha Samad, Patrick Simon Welz, Valentina M. Zinna, Thomas Mortimer, Sung Kook Chun, Kohei Shimaji, Tomoki Sato, Paul Petrus, Arun Kumar, Mireia Vaca-Dempere, Oleg Deryagian, Cassandra Van, José Manuel Monroy KuhnDominik Lutter, Marcus M. Seldin, Selma Masri, Wei Li, Pierre Baldi, Kenneth A. Dyar, Pura Muñoz-Cánoves, Salvador Aznar Benitah, Paolo Sassone-Corsi

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The mammalian circadian clock, expressed throughout the brain and body, controls daily metabolic homeostasis. Clock function in peripheral tissues is required, but not sufficient, for this task. Because of the lack of specialized animal models, it is unclear how tissue clocks interact with extrinsic signals to drive molecular oscillations. Here, we isolated the interaction between feeding and the liver clock by reconstituting Bmal1 exclusively in hepatocytes (Liver-RE), in otherwise clock-less mice, and controlling timing of food intake. We found that the cooperative action of BMAL1 and the transcription factor CEBPB regulates daily liver metabolic transcriptional programs. Functionally, the liver clock and feeding rhythm are sufficient to drive temporal carbohydrate homeostasis. By contrast, liver rhythms tied to redox and lipid metabolism required communication with the skeletal muscle clock, demonstrating peripheral clock cross-talk. Our results highlight how the inner workings of the clock system rely on communicating signals to maintain daily metabolism.

Original languageEnglish (US)
Article numbereabi7828
JournalScience Advances
Volume7
Issue number39
DOIs
StatePublished - Sep 2021
Externally publishedYes

ASJC Scopus subject areas

  • General

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