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

First Author  Greco CM Year  2021
Journal  Sci Adv Volume  7
Issue  39 Pages  eabi7828
PubMed ID  34550736 Mgi Jnum  J:314547
Mgi Id  MGI:6790507 Doi  10.1126/sciadv.abi7828
Citation  Greco CM, et al. (2021) Integration of feeding behavior by the liver circadian clock reveals network dependency of metabolic rhythms. Sci Adv 7(39):eabi7828
abstractText  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.
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