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Updated: Jul 28, 2025
Manipulation of Rhythmic Food Intake in Mice Using a Custom-Made Feeding System
Published on: December 16, 2022
Liver and muscle circadian clocks cooperate to support glucose tolerance in mice
Jacob G Smith1, Kevin B Koronowski2, Thomas Mortimer3
1Center for Epigenetics and Metabolism, U1233 INSERM, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA; Department of Medical and Life Sciences (MELIS), Pompeu Fabra University (UPF), Parc de Recerca Biomèdica de Barcelona (PRBB), 08003 Barcelona, Spain.
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.
Insights
Restoring circadian clocks in the liver and skeletal muscle, even individually, partially improves glucose metabolism. Coordinated clocks in both tissues, linked to feeding, are crucial for systemic glucose tolerance and homeostasis.
Area of Science:
- Physiology
- Metabolism
- Chronobiology
Background:
- Physiology relies on interconnected circadian clocks within cells and tissues.
- Disruption of these biological rhythms is linked to metabolic diseases.
- Understanding tissue-specific clock interactions is vital for metabolic health.
Purpose of the Study:
- To investigate the interplay between liver and skeletal muscle circadian clocks.
- To determine the sufficiency of individual tissue clocks in regulating metabolism.
- To elucidate how coordinated clocks and feeding rhythms impact systemic glucose tolerance.
Main Methods:
- Utilized genetically modified mice lacking functional circadian clocks.
- Restored clock function selectively in the liver, skeletal muscle, or both.
- Analyzed tissue glucose metabolism and systemic glucose tolerance.
Main Results:
- Individual liver or muscle clocks partially restored tissue glucose metabolism.
- Coupling of both tissue clocks with daily feeding rhythms significantly improved systemic glucose tolerance.
- Synergy involved local transcriptional control, feeding-responsive signals (e.g., insulin), and inter-tissue metabolic cycles.
Conclusions:
- Spatiotemporal coordination between liver and skeletal muscle circadian clocks is essential for maintaining systemic glucose homeostasis.
- Disruptions in this diurnal coordination can contribute to the development of metabolic diseases.
- Targeting these interconnected clocks may offer therapeutic strategies for metabolic disorders.
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