Liver and muscle circadian clocks cooperate to support glucose tolerance in mice

Physiology is regulated by interconnected cell and tissue circadian clocks. Disruption of the rhythms gener-ated by the concerted activity of these clocks is associated with metabolic disease. Here we tested the in-teractions between clocks in two critical components of organismal metabolism, liver and skeletal muscle, by rescuing clock function either in each organ separately or in both organs simultaneously in otherwise clock-less mice. Experiments showed that individual clocks are partially sufficient for tissue glucose meta-bolism, yet the connections between both tissue clocks coupled to daily feeding rhythms support systemic glucose tolerance. This synergy relies in part on local transcriptional control of the glucose machinery, feeding-responsive signals such as insulin, and metabolic cycles that connect the muscle and liver. We posit that spatiotemporal mechanisms of muscle and liver play an essential role in the maintenance of systemic glucose homeostasis and that disrupting this diurnal coordination can contribute to metabolic disease.

Automated summary

Physiology is regulated by interconnected cell and tissue circadian clocks. Disruption of these clocks' activity is associated with metabolic disease. In this study, the interactions between clocks in liver and skeletal muscle were tested. The results showed that individual clocks have partial effects on tissue glucose metabolism, but the connection between both tissue clocks, coupled with daily feeding rhythms, supports systemic glucose tolerance. This synergy relies on local transcriptional control, feeding-responsive signals, and metabolic cycles between the muscle and liver. The study highlights the importance of spatiotemporal mechanisms in maintaining systemic glucose homeostasis and the potential role of disrupting this diurnal coordination in metabolic disease.