Interplay of central and peripheral circadian clocks in energy metabolism regulation

Metabolic health founds on a homeostatic balance that has to integrate the daily changes of rest/activity and feeding/fasting cycles. A network of endogenous 24-hour circadian clocks helps to anticipate daily recurring events and adjust physiology and behavioural functions accordingly. Circadian clocks are self-sustained cellular oscillators based on a set of clock genes/proteins organised in interlocked transcriptional-translational feedback loops. The body's clocks need to be regularly reset and synchronised with each other to achieve coherent rhythmic output signals. This synchronisation is achieved by interplay of a master clock, which resides in the suprachiasmatic nucleus, and peripheral tissue clocks. This clock network is reset by time signals such as the light/dark cycle, food intake and activity. The balanced interplay of clocks is easily disturbed in modern society by shiftwork or high-energy diets, which may further promote the development of metabolic disorders. In this review, we summarise the current model of central-peripheral clock interaction in metabolic health. Different established mouse models for central or peripheral clock disruption and their metabolic phenotypes are compared and the possible relevance of clock network interaction for the development of therapeutic approaches in humans is discussed.