Project description:We mapped the genome-wide binding profiles of GR throughout the day/night cycle (ZT0-ZT4-ZT8-ZT12-ZT16-ZT20) by using ChIP-Seq in livers from control mice and mice fed High Fat Diet (HFD) for 12 weeks
Project description:We mapped the genome-wide binding profiles of GR throughout the day/night cycle (ZT0-ZT4-ZT8-ZT12-ZT16-ZT20) by using ChIP-Seq in livers from control mice and mice fed High Fat Diet (HFD) for 12 weeks
Project description:We mapped the genome-wide binding profiles of GR by using ChIP-Seq in livers from mice fed control or HFD diet after acute exogenous ligand (DEX) administration.
Project description:We mapped the genome-wide profiles of Histone H3K27 acetylation (two time points, ZT0 and ZT12) by using ChIP-Seq in livers from control mice and mice fed High Fat Diet (HFD) for 12 weeks
Project description:We investigated remodeling of the mitochondrial proteome to determine mechanisms of changes to lipid oxidation following high-fat feeding. C57BL/6J mice consumed either a high-fat diet (HFD, 60% fat) or low fat diet (LFD, 10% fat) for 12 weeks. Mice were fasted 4 hours then anaesthetized by sodium pentobarbital for tissue collection. A mitochondrial-enriched fraction was prepared from gastrocnemius muscles and underwent proteomic analysis by high-resolution mass spectrometry.
Project description:The Glucocorticoid Receptor (GR) is a potent metabolic regulator and a major drug target. While GR was shown to play various important roles in circadian biology, its rhythmic genomic actions have never been studied. Here we mapped GR’s genome-wide chromatin occupancy in mouse livers throughout the day/night cycle. We show how GR partitions metabolic processes during fasting (cellular maintenance, gluconeogenesis) and feeding (lipid and amino acid metabolism) by time-dependent binding and target gene regulation. Highlighting the dominant role GR plays in synchronizing circadian pathways, we find that the majority of oscillating genes harbor GR binding sites and depend on GR for amplitude stability . Surprisingly, this rhythmic pattern is altered by exposure to high fat diet in a ligand-independent manner. We show how the remodeling of oscillatory gene expression and GR binding result from a concomitant increase with Stat5 co-occupancy in obese mice, and that loss of GR reduces circulating glucose and triglycerides differentially during feeding and fasting. Altogether, our findings highlight GR’s fundamental role in the rhythmic orchestration of hepatic metabolism.