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 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 an...

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Detalles Bibliográficos
Autores: Smith, Jacob G., Kumar, Arun, Deryagin, Oleg, Vaca Dempere, Mireia, 1994-, Sica, Valentina, Welz, Patrick-Simon, Muñoz Cánoves, Pura, 1962-, Sassone-Corsi, Paolo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/57313
Acceso en línea:http://hdl.handle.net/10230/57313
http://dx.doi.org/10.1016/j.celrep.2023.112588
Access Level:acceso abierto
Palabra clave:Bmal1
CP: Metabolism
Autonomy
Circadian rhythms
Endocrinology
Glucose
Inter-organ crosstalk
Liver
Metabolism
Muscle
Systems biology
Descripción
Sumario: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.