| Experiment Id | GSE129518 | Name | Circadian gene expression in mouse gastrocnemius muscle after deletion of SIRT1 in SF1 neurons |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2022-03-17 |
| description | 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 insulin sensitivity of several metabolically relevant tissues fluctuates during the 24-hour period. For example, in mice 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) conveys photic inputs toentrain 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. Gastrocnemius muscle was dissected from 10-week old mice with deletion of SIRT1 in SF1 neurons (Sf1-Cre; Sirt1loxP/loxP) and intact controls (Sirt1loxP/loxP) at different Zeitgebers (0, 6, 12, 18). |
