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| Status |
Public on Jul 10, 2024 |
| Title |
LXR-dependent enhancer activation regulates the temporal organization of the liver's response to refeeding leading to lipogenic gene overshoot |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Transitions between the fed and 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) have not been explored. We examined the transcriptional and chromatin events occurring upon refeeding in mice, including kinetic behavior and molecular drivers. We found that the refeeding response is temporally-organized with the early response focused on ramping up protein translation while the later stages of refeeding drive a bifurcated lipid synthesis program. While both the cholesterol biosynthesis and lipogenesis pathways were inhibited during fasting, most cholesterol biosynthesis genes returned to their basal levels upon refeeding while most lipogenesis genes markedly overshoot above pre-fasting levels. Gene knockout, enhancer dynamics and ChIP-seq analyses revealed that lipogenic gene overshoot is dictated by LXRα. These findings from unbiased analyses unravel the mechanism behind the long-known phenomenon of refeeding fat overshoot.
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| Overall design |
Males, 8 weeks-old mice (C57BL/6J) were randomly assigned to either group (6 mice per group). The experiment started after 1 week of acclimation. The Adlib group had ad libitum access to food (Teklad TD2018) and water throughout the experiment. For the rest of the groups, food was removed at the beginning of the inactive phase (shortly after lights on, zeitgeber time 1). For the Refed groups, food was put back in the cage 24 h later while the fasted group was anesthetized and euthanized. The Refed groups were euthanized 3 h, 10 h and 24 h after food reintroduction. At each group endpoint, mice were anesthetized and euthanized (ketamine:xylazine 30:6 mg/ml) and the liver was excised.
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| Contributor(s) |
Korenfeld N, Goldstein I |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Sep 13, 2023 |
| Last update date |
Aug 05, 2024 |
| Contact name |
Ido Goldstein |
| Organization name |
The Hebrew University of Jerusalem
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| Department |
Institute of Biochemistry, Food Science and Nutrition
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| Street address |
POB 12
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| City |
Rehovot |
| ZIP/Postal code |
7610001 |
| Country |
Israel |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (15)
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| GSM7777893 |
fasting for 24h, 1 |
| GSM7777894 |
fasting for 24h, 2 |
| GSM7777895 |
fasting for 24h, 3 |
| GSM7777896 |
fasting for 24h followed by 3h of refeeding, 1 |
| GSM7777897 |
fasting for 24h followed by 3h of refeeding, 2 |
| GSM7777898 |
fasting for 24h followed by 3h of refeeding, 3 |
| GSM7777899 |
fasting for 24h followed by 10h of refeeding, 1 |
| GSM7777900 |
fasting for 24h followed by 10h of refeeding, 2 |
| GSM7777901 |
fasting for 24h followed by 10h of refeeding, 3 |
| GSM7777902 |
fasting for 24h followed by 24h of refeeding, 1 |
| GSM7777903 |
fasting for 24h followed by 24h of refeeding, 2 |
| GSM7777904 |
fasting for 24h followed by 24h of refeeding, 3 |
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| This SubSeries is part of SuperSeries: |
| GSE243057 |
Liver X receptor controls a bifurcated transcriptional program where lipogenesis genes overshoot upon refeeding while cholesterol biosynthesis genes return to pre-fasting levels |
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| Relations |
| BioProject |
PRJNA1016288 |
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