Deletion of Rictor in Brain and Fat Alters Peripheral Clock Gene Expression and Increases Blood Pressure

Drägert, Katja and Bhattacharya, Indranil and Pellegrini, Giovanni and Seebeck, Petra and Azzi, Abdelhalim and Brown, Steven A. and Georgiopoulou, Stavroula and Held, Ulrike and Blyszczuk, Przemyslaw and Arras, Margarete and Humar, Rok and Hall, Michael N. and Battegay, Edouard and Haas, Elvira. (2015) Deletion of Rictor in Brain and Fat Alters Peripheral Clock Gene Expression and Increases Blood Pressure. Hypertension, 66 (2). pp. 332-339.

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Official URL: http://edoc.unibas.ch/dok/A6411185

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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 the regulation of glucose and lipid metabolism. In the perivascular adipose tissue, 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 (Rictor(aP2KO)) mice generated using adipocyte protein-2 gene promoter-driven CRE recombinase expression to delete Rictor. The 24-hour mean arterial pressure was increased in Rictor(aP2KO) mice, and the physiological decline in mean arterial pressure during the dark period was 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, and their receptor expression in adipocytes. Moreover, clock gene expression was reduced or phase-shifted in perivascular adipose tissue. No differences in clock gene expression were observed in the master clock suprachiasmatic nucleus, although Rictor gene expression was also lower in brain of Rictor(aP2KO) mice. Thus, this study highlights the importance of RICTOR/mTORC2 for interactions between vasculature, adipocytes, and brain to tune physiological outcomes, such as blood pressure and locomotor activity.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
UniBasel Contributors:Hall, Michael N.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Heart Association
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:09 Nov 2017 08:14
Deposited On:02 Oct 2015 10:00

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