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

研究成果: Article査読

8 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)2385-2398.e3
ジャーナルCell Reports
27
8
DOI
出版ステータスPublished - 2019 5 21
外部発表はい

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)

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