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| Status |
Public on Jul 05, 2015 |
| Title |
Deletion of Rictor in brain and fat alters peripheral clock gene expression and increases blood pressure |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The mammalian target of rapamycin complex 2 (mTORC2) contains the essential protein RICTOR and is activated by growth factors. mTORC2 in adipose tissue contributes to regulating glucose and lipid metabolism. In the perivascular adipose tissue (PVAT) mTORC2 ensures normal vascular reactivity by controlling expression of inflammatory molecules. To assess whether RICTOR/mTORC2 contributes to blood pressure regulation, we applied a radiotelemetry approach in control and Rictor knockout (RictoraP2KO) mice generated by using adipocyte protein-2 gene promoter-driven CRE recombinase to delete Rictor. 24 hour mean arterial pressure (MAP) was increased in RictoraP2KO mice, and the physiologic decline in MAP during the dark period impaired. In parallel, heart rate and locomotor activity were elevated during the dark period with a pattern similar to blood pressure changes. This phenotype was associated with mild cardiomyocyte hypertrophy, decreased cardiac natriuretic peptides (NPs) and NP receptor expression in adipocytes. Moreover, clock gene expression was dampened or phase-shifted in PVAT. No differences in clock gene expression were observed in the master clock suprachiasmatic nucleus (SCN), though Rictor gene expression was also lower in brain of RictoraP2KO mice. Thus, the present study underscores the importance of RICTOR/mTORC2 for interactions between vasculature, adipocytes and brain to tune physiological outcomes such as blood pressure and locomotion.
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| Overall design |
Gene expression in PVAT of RictoraP2KO mice was compared to controls (Rictorfl/fl) mice.
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| Contributor(s) |
Drägert K, Bhattacharya I, Pellegrini G, Seebeck P, Azzi A, Brown S, Georgiopoulou S, Held U, Arras M, Humar R, Hall MN, Battegay E, Haas E |
| Citation(s) |
26101345 |
| Submission date |
Mar 19, 2015 |
| Last update date |
Apr 18, 2017 |
| Contact name |
Elvira Haas |
| E-mail(s) |
elvira.haas@usz.ch
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| Organization name |
University Hospital of Zurich
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| Department |
Division of Internal Medicine
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| Street address |
Wagistrasse 12, 3rd floor
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| City |
Schlieren |
| ZIP/Postal code |
8952 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL11533 |
[MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA278865 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE67077_RAW.tar |
32.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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