Cell Reports (Jun 2023)
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. Parker,
- Pierre Baldi,
- Patrick-Simon Welz,
- Cholsoon Jang,
- Selma Masri,
- Salvador Aznar Benitah,
- Pura Muñoz-Cánoves,
- Paolo Sassone-Corsi
Affiliations
- Jacob G. Smith
- Center 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; Corresponding author
- Kevin B. Koronowski
- Center for Epigenetics and Metabolism, U1233 INSERM, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA; Department of Biochemistry and Structural Biology, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Corresponding author
- Thomas Mortimer
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain
- Tomoki Sato
- Center for Epigenetics and Metabolism, U1233 INSERM, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA; Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
- Carolina M. Greco
- Center for Epigenetics and Metabolism, U1233 INSERM, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy
- Paul Petrus
- Center for Epigenetics and Metabolism, U1233 INSERM, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA; Department of Medicine (H7), Karolinska Institutet, 141 86 Stockholm, Sweden
- Amandine Verlande
- Department of Biological Chemistry, Center for Epigenetics and Metabolism, Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA 92697, USA
- Siwei Chen
- Institute for Genomics and Bioinformatics, Department of Computer Science, University of California, Irvine, Irvine, CA 92697, USA
- Muntaha Samad
- Institute for Genomics and Bioinformatics, Department of Computer Science, University of California, Irvine, Irvine, CA 92697, USA
- Ekaterina Deyneka
- Institute for Genomics and Bioinformatics, Department of Computer Science, University of California, Irvine, Irvine, CA 92697, USA
- Lavina Mathur
- Department of Biological Chemistry, Center for Epigenetics and Metabolism, Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA 92697, USA
- Ronnie Blazev
- Centre for Muscle Research, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, VIC 3010, Australia
- Jeffrey Molendijk
- Centre for Muscle Research, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, VIC 3010, Australia
- Arun Kumar
- Department of Medical and Life Sciences (MELIS), Pompeu Fabra University (UPF), Parc de Recerca Biomèdica de Barcelona (PRBB), 08003 Barcelona, Spain
- Oleg Deryagin
- Department of Medical and Life Sciences (MELIS), Pompeu Fabra University (UPF), Parc de Recerca Biomèdica de Barcelona (PRBB), 08003 Barcelona, Spain
- Mireia Vaca-Dempere
- Department of Medical and Life Sciences (MELIS), Pompeu Fabra University (UPF), Parc de Recerca Biomèdica de Barcelona (PRBB), 08003 Barcelona, Spain
- Valentina Sica
- Department of Medical and Life Sciences (MELIS), Pompeu Fabra University (UPF), Parc de Recerca Biomèdica de Barcelona (PRBB), 08003 Barcelona, Spain
- Peng Liu
- King Abdullah University of Science and Technology, KAUST Environmental Epigenetics Research Program, Biological and Environmental Sciences and Engineering Division, Thuwal 23955, Saudi Arabia
- Valerio Orlando
- King Abdullah University of Science and Technology, KAUST Environmental Epigenetics Research Program, Biological and Environmental Sciences and Engineering Division, Thuwal 23955, Saudi Arabia
- Benjamin L. Parker
- Centre for Muscle Research, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, VIC 3010, Australia
- Pierre Baldi
- Institute for Genomics and Bioinformatics, Department of Computer Science, University of California, Irvine, Irvine, CA 92697, USA
- Patrick-Simon Welz
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain; Program in Cancer Research, Hospital del Mar Medical Research Institute (IMIM), Parc de Recerca Biomèdica de Barcelona (PRBB), 08003 Barcelona, Spain
- Cholsoon Jang
- Department of Biological Chemistry, Center for Epigenetics and Metabolism, Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA 92697, USA
- Selma Masri
- Department of Biological Chemistry, Center for Epigenetics and Metabolism, Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA 92697, USA
- Salvador Aznar Benitah
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain; Corresponding author
- Pura Muñoz-Cánoves
- Department of Medical and Life Sciences (MELIS), Pompeu Fabra University (UPF), Parc de Recerca Biomèdica de Barcelona (PRBB), 08003 Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain; Altos Labs, Inc., San Diego Institute of Science, San Diego, CA 92121, USA; Corresponding author
- Paolo Sassone-Corsi
- Center for Epigenetics and Metabolism, U1233 INSERM, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA
- Journal volume & issue
-
Vol. 42,
no. 6
p. 112588
Abstract
Summary: 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.
