Document Detail


The brain subfornical organ mediates leptin-induced increases in renal sympathetic activity but not its metabolic effects.
MedLine Citation:
PMID:  23357182     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The adipocyte-derived hormone leptin acts within the central nervous system to decrease food intake and body weight and to increase renal and thermogenic brown adipose tissue sympathetic nerve activity (SNA). Previous studies have focused on hypothalamic brain regions, although recent findings have identified leptin receptors (ObR) in a distributed brain network, including the circumventricular subfornical organ (SFO), a forebrain region devoid of a blood-brain barrier. We tested the hypothesis that ObR in the SFO are functionally linked to leptin-induced decreases in food intake and body weight and increases in SNA. SFO-targeted microinjections of an adenovirus encoding Cre-recombinase in ObR(flox/flox) mice resulted in selective ablation of ObR in the SFO. Interestingly, deletion of ObR in the SFO did not influence the decreases in either food intake or body weight in response to daily systemic or cerebroventricular administration of leptin. In line with these findings, reduction in SFO ObR did not attenuate leptin-mediated increases in thermogenic brown adipose tissue SNA. In contrast, increases in renal SNA induced by systemic or cerebroventricular administration of leptin were abolished in mice with SFO-targeted deletion of ObR. These results demonstrate that ObR in the SFO play an important role in leptin-induced renal sympathoexcitation, but not in the body weight, food intake, or brown adipose tissue SNA thermogenic effects of leptin. These findings highlight the concept of a distributed brain network of leptin action and illustrate that brain regions, including the SFO, can mediate distinct cardiovascular and metabolic responses to leptin.
Authors:
Colin N Young; Donald A Morgan; Scott D Butler; Allyn L Mark; Robin L Davisson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-28
Journal Detail:
Title:  Hypertension     Volume:  61     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-14     Completed Date:  2013-04-12     Revised Date:  2014-03-06    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  737-44     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue, Brown / drug effects,  innervation,  metabolism
Animals
Body Weight / drug effects
Brain / drug effects
Eating / drug effects
Gene Silencing
Injections, Intraventricular
Kidney / drug effects*,  innervation
Leptin / administration & dosage*
Male
Mice
Receptors, Leptin / genetics
Subfornical Organ / drug effects*
Sympathetic Nervous System / drug effects*
Thermogenesis / drug effects
Grant Support
ID/Acronym/Agency:
HL063887/HL/NHLBI NIH HHS; HL084207/HL/NHLBI NIH HHS; HL096571/HL/NHLBI NIH HHS; P01 HL084207/HL/NHLBI NIH HHS; P01 HL096571/HL/NHLBI NIH HHS; R01 HL063887/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Leptin; 0/Receptors, Leptin; 0/leptin receptor, mouse
Comments/Corrections

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