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

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-Dempere, Valentina Sica, Peng Liu, Valerio Orlando, Benjamin L. ParkerPierre Baldi, Patrick Simon Welz, Cholsoon Jang, Selma Masri, Salvador Aznar Benitah, Pura Muñoz-Cánoves, Paolo Sassone-Corsi

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Article number112588
JournalCell Reports
Volume42
Issue number6
DOIs
StatePublished - Jun 27 2023

Keywords

  • Bmal1
  • CP: Metabolism
  • autonomy
  • circadian rhythms
  • endocrinology
  • glucose
  • inter-organ crosstalk
  • liver
  • metabolism
  • muscle
  • systems biology

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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