Document Detail

Effects of chronic central leptin infusion on proopiomelanocortin and neurotensin gene expression in the rat hypothalamus.
MedLine Citation:
PMID:  18562101     Owner:  NLM     Status:  MEDLINE    
Leptin signaling in the hypothalamus is critical for normal food intake and body weight regulation. While hyperleptinemia in obese people suggests a state of leptin resistance, the mechanism is not clearly understood. In a rat model of central leptin infusion in which animals develop resistance to the satiety action of leptin, orexigenic peptide producing neuropeptide Y neurons in the hypothalamus develop leptin resistance. However, it is still unknown if increased hypothalamic leptin tone caused by central leptin infusion results in the development of leptin resistance in anorexigenic peptide producing proopiomelanocortin (POMC) and neurotensin (NT) neurons. To this end, male rats were infused chronically with leptin (160 ng/h) or vehicle into the lateral cerebroventricle for 16 days. On day 4 of leptin infusion when food intake was decreased, POMC and NT mRNA levels, as determined by RNAse protection assay, were significantly increased as compared to control. By contrast, on day 16 of leptin infusion, when food intake was mostly normalized, both POMC and NT mRNA levels remained unchanged compared with control. These findings suggest the development of leptin resistance in the POMC and NT neurons following chronic elevation of hypothalamic leptin tone, which may be involved in the development of resistance to the satiety action of leptin following central infusion of this peptide hormone.
Abhiram Sahu
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-05-28
Journal Detail:
Title:  Neuroscience letters     Volume:  440     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-06-23     Completed Date:  2008-09-15     Revised Date:  2010-09-22    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  125-9     Citation Subset:  IM    
Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Magee-Womens Research Institute, 204 Craft Avenue, Room B303, Pittsburgh, PA 15213, USA.
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MeSH Terms
Appetite Regulation / drug effects
Body Weight / drug effects
Eating / drug effects
Gene Expression / drug effects*
Hypothalamus / drug effects*,  metabolism
Injections, Intraventricular
Leptin / administration & dosage,  pharmacology*
Neurons / drug effects,  metabolism
Neurotensin / genetics*
Nuclease Protection Assays / methods
Pro-Opiomelanocortin / genetics*
RNA, Messenger / genetics,  isolation & purification,  metabolism
Rats, Sprague-Dawley
Time Factors
Grant Support
Reg. No./Substance:
0/Leptin; 0/RNA, Messenger; 39379-15-2/Neurotensin; 66796-54-1/Pro-Opiomelanocortin

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