Light Entrains Diurnal Changes in Insulin Sensitivity of Skeletal Muscle via Ventromedial Hypothalamic Neurons.

Aras E; Ramadori G; Kinouchi K; Liu Y; Ioris RM; Brenachot X; Ljubicic S; Veyrat-Durebex C; Mannucci S; Galié M; Baldi P; Sassone-Corsi P; Coppari R

doi:10.1016/j.celrep.2019.04.093

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Journal article

Light Entrains Diurnal Changes in Insulin Sensitivity of Skeletal Muscle via Ventromedial Hypothalamic Neurons.

Aras E 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.
Ramadori G 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. Electronic address: giorgio.ramadori@unige.ch.
Kinouchi K Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA 92607, USA.
Liu Y Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California Irvine, Irvine, CA 92697, USA.
Ioris RM 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.
Brenachot X 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.
Ljubicic S 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.
Veyrat-Durebex C 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.
Mannucci S Department of Neuroscience, Biomedicine and Movement, University of Verona, Piazzale L.A. Scuro 10, Verona 37134, Italy.
Galié M Department of Neuroscience, Biomedicine and Movement, University of Verona, Piazzale L.A. Scuro 10, Verona 37134, Italy.
Baldi P Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California Irvine, Irvine, CA 92697, USA.
Sassone-Corsi P Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA 92607, USA.
Coppari R 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. Electronic address: roberto.coppari@unige.ch.

2019-05-23

Published in:

Cell reports. - 2019

Ventromedial Hypothalamic Nucleus

English 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.

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