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

doi:10.1016/j.celrep.2019.04.093

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

Cell Rep. 2019 May 21;27(8):2385-2398.e3. doi: 10.1016/j.celrep.2019.04.093.

Authors

Affiliations

¹ 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.
² 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.
³ Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA 92607, USA.
⁴ Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California Irvine, Irvine, CA 92697, USA.
⁵ Department of Neuroscience, Biomedicine and Movement, University of Verona, Piazzale L.A. Scuro 10, Verona 37134, Italy.
⁶ 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.

PMID: 31116983
DOI: 10.1016/j.celrep.2019.04.093

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Circadian Rhythm
Humans
Insulin / metabolism*
Mice
Muscle, Skeletal / metabolism*
Phototherapy / methods*
Ventromedial Hypothalamic Nucleus / physiopathology*

Substances

Insulin