Journal article
Hypothalamic mTORC1 Signaling Controls Sympathetic Nerve Activity and Arterial Pressure and Mediates Leptin Effects
Cell metabolism, Vol.17(4), pp.599-606
04/02/2013
DOI: 10.1016/j.cmet.2013.02.017
PMCID: PMC3657313
PMID: 23541372
Abstract
The fundamental importance of the hypothalamus in the regulation of autonomic and cardiovascular functions is well established. However, the molecular processes involved are not well understood. Here, we show that the mammalian (or mechanistic) target of rapamycin (mTOR) signaling in the hypothalamus is tied to the activity of the sympathetic nervous system and cardiovascular function. Modulation of mTORC1 signaling caused dramatic changes in sympathetic traffic, blood flow and arterial pressure. Our data also demonstrate the importance of hypothalamic mTORC1 signaling in transducing the sympathetic and cardiovascular actions of leptin. Moreover, we show that PI3K pathway links the leptin receptor to mTORC1 signaling and changes in its activity impacts the sympathetic traffic and arterial pressure. These findings establish mTORC1 activity in the hypothalamus as a key determinant of sympathetic and cardiovascular regulation and suggest that dysregulated hypothalamic mTORC1 activity may influence the development of cardiovascular diseases.
Details
- Title: Subtitle
- Hypothalamic mTORC1 Signaling Controls Sympathetic Nerve Activity and Arterial Pressure and Mediates Leptin Effects
- Creators
- Shannon M Harlan - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IowaDeng-Fu Guo - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IowaDonald A Morgan - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IowaCaroline Fernandes-Santos - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IowaKamal Rahmouni - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Cell metabolism, Vol.17(4), pp.599-606
- DOI
- 10.1016/j.cmet.2013.02.017
- PMID
- 23541372
- PMCID
- PMC3657313
- ISSN
- 1550-4131
- eISSN
- 1932-7420
- Grant note
- P01 HL014388 || HL / National Heart, Lung, and Blood Institute : NHLBI
- Language
- English
- Date published
- 04/02/2013
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040485502771
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