Document Detail


Silencing of estrogen receptor alpha in the ventromedial nucleus of hypothalamus leads to metabolic syndrome.
MedLine Citation:
PMID:  17284595     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Estrogen receptor alpha (ERalpha) plays a pivotal role in the regulation of food intake and energy expenditure by estrogens. Although it is well documented that a disruption of ERalpha signaling in ERalpha knockout (ERKO) mice leads to an obese phenotype, the sites of estrogen action and mechanisms underlying this phenomenon are still largely unknown. In the present study, we exploited RNA interference mediated by adeno-associated viral vectors to achieve focused silencing of ERalpha in the ventromedial nucleus of the hypothalamus, a key center of energy homeostasis. After suppression of ERalpha expression in this nucleus, female mice and rats developed a phenotype characteristic for metabolic syndrome and marked by obesity, hyperphagia, impaired tolerance to glucose, and reduced energy expenditure. This phenotype persisted despite normal ERalpha levels elsewhere in the brain. Although an increase in food intake preceded weight gain, our data suggest that a leading factor of obesity in this model is likely a decline in energy expenditure with all three major constituents being affected, including voluntary activity, basal metabolic rate, and diet-induced thermogenesis. Together, these findings indicate that ERalpha in the ventromedial nucleus of the hypothalamus neurons plays an essential role in the control of energy balance and the maintenance of normal body weight.
Authors:
Sergei Musatov; Walter Chen; Donald W Pfaff; Charles V Mobbs; Xue-Jun Yang; Deborah J Clegg; Michael G Kaplitt; Sonoko Ogawa
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-02-06
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  104     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-02-14     Completed Date:  2007-05-17     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2501-6     Citation Subset:  IM    
Affiliation:
Neurologix, Inc., Fort Lee, NJ 07024, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Animals
Basal Metabolism
Energy Metabolism
Estrogen Receptor alpha / genetics*,  physiology
Metabolic Syndrome X / etiology*,  metabolism
Mice
Obesity / etiology
RNA Interference*
Thermogenesis
Ventromedial Hypothalamic Nucleus / chemistry,  physiology*
Grant Support
ID/Acronym/Agency:
MH62147/MH/NIMH NIH HHS; MH67775/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Estrogen Receptor alpha
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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