Document Detail

Impaired anorectic effect of leptin in neurotensin receptor 1-deficient mice.
MedLine Citation:
PMID:  18639588     Owner:  NLM     Status:  MEDLINE    
Neurotensin plays a role in regulating feeding behavior. Central injection of neurotensin reduces food intake and the anorectic effect of neurotensin is mediated through neurotensin receptor 1 (Ntsr1). Ntsr1-deficient mice are characterized by mild hyperphagia and overweight without hyperleptinemia. The mechanism by which Ntsr1-deficient mice develop these metabolic abnormalities is not well understood. Leptin, secreted by adipocytes, regulates food intake by acting on hypothalamic neurons including neurotensin-producing neurons. Since the anorectic effect of leptin is blocked by neurotensin receptor antagonist, we hypothesized that the anorectic effect of leptin is mediated through Ntsr1 in the central nervous system and that decreased sensitivity to the anorectic effect of leptin contributes to metabolic perturbations in Ntsr1-deficient mice. To address this hypothesis, we examined the effect of intracerebroventricular (i.c.v.) administration of leptin on food intake in Ntsr1-deficient mice. A single i.c.v. injection of leptin caused robust reductions in food intake in wild-type mice. These effects were markedly attenuated in Ntsr1-deficient mice. These data are consistent with our hypothesis that the anorectic effect of leptin is at least partly mediated through central Ntsr1 and that the leptin-Ntsr1 signaling pathway is involved in the regulation of food intake. Our data also suggest that the lack of Ntsr1 reduces sensitivity to the anorectic action of leptin, causing hyperphagia and abnormal weight gain.
Eun Ran Kim; Arnold Leckstrom; Tooru M Mizuno
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-01
Journal Detail:
Title:  Behavioural brain research     Volume:  194     ISSN:  0166-4328     ISO Abbreviation:  Behav. Brain Res.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-09-01     Completed Date:  2009-01-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8004872     Medline TA:  Behav Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  66-71     Citation Subset:  IM    
Department of Physiology, University of Manitoba, Winnipeg, MB, Canada.
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MeSH Terms
Analysis of Variance
Appetite Depressants / therapeutic use*
Behavior, Animal
Blood Glucose / drug effects,  genetics
Body Temperature / drug effects,  genetics
Body Weight / drug effects,  genetics
Eating / drug effects,  genetics
Gene Expression Regulation / drug effects,  genetics
Hyperphagia / drug therapy*,  genetics*
Hypothalamus / drug effects,  metabolism
Leptin / therapeutic use*
Mice, Inbred C57BL
Mice, Knockout
Motor Activity / drug effects,  genetics
Neurotensin / genetics,  metabolism
Receptors, Neurotensin / deficiency*,  genetics,  metabolism
Reg. No./Substance:
0/Appetite Depressants; 0/Blood Glucose; 0/Leptin; 0/Ntsr2 protein, mouse; 0/Receptors, Neurotensin; 0/neurotensin type 1 receptor; 39379-15-2/Neurotensin

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

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