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Status |
Public on Mar 16, 2015 |
Title |
Liver Med23 ablation improves glucose and lipid metabolism and prevent diet-induced obesity |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Mediator complex function as an integrative hub for transcriptional regulation. Here we show that Mediator subunit MED23 regulate glucose and lipid metabolism via FOXO1 in liver. Here, we have generated a liver-specific Med23-knockout (LMKO) mouse and found that Med23-deletion in liver improved glucose and lipid metabolism, as well as insulin responsiveness, and prevented diet-induced obesity. Mechanistically, MED23 participated in gluconeogenesis and cholesterol synthesis by interacting with FOXO1. Disruption of this interaction by hepatic Med23-deletion impaired the Mediator and RNAP II recruitment and partially reduced the expression of the FOXO1 target genes. Remarkably, acute hepatic Med23 knockdown in db/db mice significantly improved insulin sensitivity. Overall, our data revealed Mediator MED23 as a critical regulator of glucose and lipid metabolism, suggesting novel therapeutic strategies against metabolic diseases.
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Overall design |
Comparison of mRNA expression profile of control and LMKO mice fasted 24 h (fasted) or fasted 24 h then re-fed 24 h (re-fed) (n = 2 per group)
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Contributor(s) |
Chu Y, Xu Y, Yao X, Wang G |
Citation(s) |
25223702 |
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Submission date |
Jul 17, 2013 |
Last update date |
May 15, 2019 |
Contact name |
Yajing Chu |
E-mail(s) |
chuyajing@ihcams.ac.cn
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Phone |
86-22-23909396
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Organization name |
Institute of Hematology, Chinese Academy of Medical Sciences
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Department |
State Key Laboratory of Experimental Hematology
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Lab |
Weiping Yuan Lab
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Street address |
Nanjing Road 288
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City |
Tianjin |
ZIP/Postal code |
300020 |
Country |
China |
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Platforms (1) |
GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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Samples (8)
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Relations |
BioProject |
PRJNA212436 |
SRA |
SRP027536 |