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| Status |
Public on Jun 21, 2013 |
| Title |
RAP1 protects from obesity, diabetes and metabolic syndrome through its extra telomeric role regulating gene expression (old mouse liver) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
RAP1 is one of the components of shelterin, the capping complex at chromosome ends or telomeres. Unlike other shelterins, however, RAP1 is not essential for preventing telomere fusions. RAP1 also binds along chromosome arms, where it is proposed to regulate gene expression. To investigate the non-telomeric roles of RAP1 in vivo, we generated a RAP1 whole-body knock-out mouse model. Unexpectedly, these mice presented an early onset of obesity, which was particularly severe in females and was aggravated under a high-fat diet. Rap1-deficient mice showed abnormal accumulation of fat in abdominal depots and developed signs of type II diabetes and metabolic syndrome, including hepatic steatosis and high fasting plasma levels of insulin, glucose, cholesterol, and alanine transaminase. Gene expression analyses of the liver and visceral white fat from Rap1-deficient mice before the onset of obesity indicated deregulation of key metabolic transcriptional programs including fatty acid metabolism, PPARa signalling and glucose metabolism. Transcriptome and Western blotting analyses in liver further identified Ppara and Pgc1a and their target genes as the key metabolic pathways affected by Rap1 deletion. Finally, we show here that RAP1 binds to Ppara and Pgc1a loci and modulates their transcription. These findings underscore an unprecedented role for a telomere-binding protein in the regulation of metabolism.
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| Overall design |
2 condition experiment: WT versus Rap1 knockout. Tissue: liver. 3 biological replicates per genotype. Mice were 30 weeks old.
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| Contributor(s) |
Martínez P, Gómez-López G, García F, Flores JM, Blasco MA |
| Citation(s) |
23791526 |
| Submission date |
Dec 27, 2012 |
| Last update date |
Feb 02, 2018 |
| Contact name |
Paula Martinez |
| E-mail(s) |
pmartinez@cnio.es
|
| Organization name |
CNIO
|
| Street address |
Melchor Fernandez Almagro 3
|
| City |
Madrid |
| State/province |
Madrid |
| ZIP/Postal code |
28029 |
| Country |
Spain |
| |
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| Platforms (1) |
| GPL10787 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE43174 |
RAP1 protects from obesity, diabetes and metabolic syndrome through its extra telomeric role regulating gene expression |
|
| Relations |
| BioProject |
PRJNA184841 |
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