GSE169483
Integration of Feeding Behaviour by the Liver Circadian Clock Reveals Network Dependency of Metabolic Rhythms [ChIP-seq]
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. Due to lack of specialized animal models, it is unclear how tissue clocks interact with extrinsic signals to drive molecular oscillations. Here, we present a model in which the interaction between feeding and the liver clock can be isolated in vivo by reconstituting Bmal1 exclusively in hepatocytes (Liver-RE) in otherwise clock-less mice. 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 glucose 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.   Overall design: WT, BMAL1 KO and BMAL1 Liver reconstituted mice (Liver-RE) were fed ad libitum (AL) or feeding was restricted to 12 hours during the night (night feeding, NF). ChIP for CEBPB was performed on livers  collected at two circadian time points (zeitgeber time ZT8 and ZT20).