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Liver X receptor controls a bifurcated transcriptional program where lipogenesis genes overshoot upon refeeding while cholesterol biosynthesis genes return to pre-fasting levels [lxr_chip]

GSE243051 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2024/07/10 Platform GPL13112
Summary
Transitions from a fed to a fasted state are common in mammals. The liver orchestrates adaptive responses to feeding/fasting by transcriptionally regulating metabolic pathways of energy usage and storage. Transcriptional and enhancer dynamics following cessation of fasting (refeeding) were never explored. We aimed to inspect the transcriptional and chromatin events occurring upon refeeding, their kinetic behavior and their molecular drivers. We found that the refeeding response is temporally-organized with an early response focused on ramping up protein translation while later stages of refeeding drive a bifurcated lipid synthesis program. While both lipid synthesis pathways were inhibited during fasting, cholesterol biosynthesis genes returned to their basal levels upon refeeding while lipogenesis genes significantly overshoot above pre-fasting levels. Lipogenic gene overshoot is dictated by Liver X Receptor alpha (LXRα) which directly binds and activates lipogenic enhancers. These findings unravel the mechanism behind the long-known phenomenon of refeeding fat overshoot.
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Direct links to NCBI, no account and no request form: the whole study as GSE243051_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1016296 and SRA study SRP460171. Searching any of these in the dataset finder brings you back here.

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