|Open Access Gold|
Integration of feeding behavior by the liver circadian clock reveals network dependency of metabolic rhythms.
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.
Zymo-CEM Postdoctoral Fellowship (Zymo Research)
European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant
Novo Nordisk Foundation
Worldwide Cancer Research Foundation (WCRF)
Government of Spain (MINECO)
Government of Cataluna (SGR grant)
European Research Council (ERC)
Severo-Ochoa-Program for Centers of Excellence
Maria-deMaeztu-Program for Units of Excellence
La Marato/TV3 Foundation
Spanish Ministry of Science and Innovation (MICINN)
Cancer Center Support Grant at the UCI
National Cancer Institute of the National Institutes of Health (NIH)