| Impaired anorectic effect of leptin in neurotensin receptor 1-deficient mice. | |
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MedLine Citation:
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PMID: 18639588 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Eun Ran Kim; Arnold Leckstrom; Tooru M Mizuno |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-07-01 |
Journal Detail:
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Title: Behavioural brain research Volume: 194 ISSN: 0166-4328 ISO Abbreviation: Behav. Brain Res. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-09-01 Completed Date: 2009-01-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8004872 Medline TA: Behav Brain Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 66-71 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Manitoba, Winnipeg, MB, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Appetite Depressants / therapeutic use* Behavior, Animal Blood Glucose / drug effects, genetics Body Temperature / drug effects, genetics Body Weight / drug effects, genetics Calorimetry Eating / drug effects, genetics Gene Expression Regulation / drug effects, genetics Hyperphagia / drug therapy*, genetics* Hypothalamus / drug effects, metabolism Leptin / therapeutic use* Mice Mice, Inbred C57BL Mice, Knockout Motor Activity / drug effects, genetics Neurotensin / genetics, metabolism Receptors, Neurotensin / deficiency*, genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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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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