Light Entrains Diurnal Changes in Insulin Sensitivity of Skeletal Muscle via Ventromedial Hypothalamic Neurons
Ebru Aras,
Giorgio Ramadori,
Kenichiro Kinouchi,
Yu Liu,
Rafael M. Ioris,
Xavier Brenachot,
Sanda Ljubicic,
Christelle Veyrat-Durebex,
Silvia Mannucci,
Mirco Galié,
Pierre Baldi,
Paolo Sassone-Corsi,
Roberto Coppari
Affiliations
Ebru Aras
Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland
Giorgio Ramadori
Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Corresponding author
Kenichiro Kinouchi
Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA 92607, USA
Yu Liu
Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California Irvine, Irvine, CA 92697, USA
Rafael M. Ioris
Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland
Xavier Brenachot
Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland
Sanda Ljubicic
Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland
Christelle Veyrat-Durebex
Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland
Silvia Mannucci
Department of Neuroscience, Biomedicine and Movement, University of Verona, Piazzale L.A. Scuro 10, Verona 37134, Italy
Mirco Galié
Department of Neuroscience, Biomedicine and Movement, University of Verona, Piazzale L.A. Scuro 10, Verona 37134, Italy
Pierre Baldi
Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California Irvine, Irvine, CA 92697, USA
Paolo Sassone-Corsi
Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA 92607, USA
Roberto Coppari
Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA 92607, USA; Corresponding author
Summary: Loss of synchrony between geophysical time and insulin action predisposes to metabolic diseases. Yet the brain and peripheral pathways linking proper insulin effect to diurnal changes in light-dark and feeding-fasting inputs are poorly understood. Here, we show that the insulin sensitivity of several metabolically relevant tissues fluctuates during the 24 h period. For example, in mice, the insulin sensitivity of skeletal muscle, liver, and adipose tissue is lowest during the light period. Mechanistically, by performing loss- and gain-of-light-action and food-restriction experiments, we demonstrate that SIRT1 in steroidogenic factor 1 (SF1) neurons of the ventromedial hypothalamic nucleus (VMH) convey photic inputs to entrain the biochemical and metabolic action of insulin in skeletal muscle. These findings uncover a critical light-SF1-neuron-skeletal-muscle axis that acts to finely tune diurnal changes in insulin sensitivity and reveal a light regulatory mechanism of skeletal muscle function. : Aras et al. provide in vivo evidence that tissue responsiveness to insulin varies in a diurnal fashion. In skeletal muscle, the authors show that photic inputs entrain diurnal changes in clock genes expression and insulin sensitivity via SIRT1 in neurons within the hypothalamic ventromedial nucleus.
