Document Detail


Hypothalamic mTORC1 signaling controls sympathetic nerve activity and arterial pressure and mediates leptin effects.
MedLine Citation:
PMID:  23541372     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 to cardiovascular function. Modulation of mTOR complex 1 (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 the PI3K pathway links the leptin receptor to mTORC1 signaling and that changes in its activity impact 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.
Authors:
Shannon M Harlan; Deng-Fu Guo; Donald A Morgan; Caroline Fernandes-Santos; Kamal Rahmouni
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell metabolism     Volume:  17     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-05-16     Completed Date:  2013-09-27     Revised Date:  2014-04-04    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  599-606     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Arterial Pressure / drug effects
Class I Phosphatidylinositol 3-Kinases / antagonists & inhibitors,  genetics,  metabolism
Hypothalamus / metabolism*
Leptin / metabolism*
Leucine / pharmacology
Mice
Mice, Inbred C57BL
Multiprotein Complexes
Phosphatidylinositol 3-Kinases / antagonists & inhibitors,  metabolism
Phosphorylation
Proteins / antagonists & inhibitors,  metabolism*
RNA Interference
RNA, Small Interfering / metabolism
Rats
Rats, Sprague-Dawley
Receptors, Leptin / metabolism
Ribosomal Protein S6 Kinases, 70-kDa / metabolism
Signal Transduction / drug effects
Sirolimus / pharmacology
Sympathetic Nervous System / drug effects,  metabolism
TOR Serine-Threonine Kinases
Grant Support
ID/Acronym/Agency:
HL014388/HL/NHLBI NIH HHS; HL084207/HL/NHLBI NIH HHS; P01 HL014388/HL/NHLBI NIH HHS; P01 HL084207/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Leptin; 0/Multiprotein Complexes; 0/Proteins; 0/RNA, Small Interfering; 0/Receptors, Leptin; 0/mechanistic target of rapamycin complex 1; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.1.137/Class I Phosphatidylinositol 3-Kinases; EC 2.7.1.137/p110delta protein, rat; EC 2.7.11.1/Ribosomal Protein S6 Kinases, 70-kDa; GMW67QNF9C/Leucine; W36ZG6FT64/Sirolimus
Comments/Corrections

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