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

by Jacob G. Smith, Kevin B. Koronowski, Thomas Mortimer, Tomoki Sato , Carolina M. Greco, Paul Petrus , Amandine Verlande, Siwei Chen , Muntaha Samad, Ekaterina Deyneka, Lavina Mathur, Ronnie Blazev, Jeffrey Molendijk, Arun Kumar, Oleg Deryagin, Mireia Vaca-, Ronnie Blazev, Jeffrey Molendijk, Arun Kumar, Oleg Deryagin, Mireia Vaca-Dempere,, Valentina Sica, Peng Liu,, Valerio Orlando,, Benjamin L. Parker Paolo Sassone-Corsi
Year: 2023 DOI: https://doi.org/10.1016/j.celrep.2023.112588

Extra Information

27 June 2023, 112588

Abstract

Physiology is regulated by interconnected cell and tissue circadian clocks. Disruption of the rhythms generated by the concerted activity of these clocks is associated with metabolic disease. Here we tested the interactions 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 metabolism, 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.