Document Detail


Leptin analog antagonizes leptin effects on food intake and body weight but mimics leptin-induced vagal afferent activation.
MedLine Citation:
PMID:  17363463     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A recombinantly produced murine leptin analog (MLA) antagonizes leptin-induced signaling in cell lines that express the long form of the leptin receptor. However, the effects of MLA on the activity of leptin-sensitive neurons and on central neural controls of food intake have not been reported. Here we report effects of MLA on food intake and body weight in adult rats and on the activity of cultured rat vagal afferent neurons. Daily intracerebroventricular coinjection of MLA with exogenous leptin significantly attenuated leptin-induced reduction of 48-h food intake and body weight. Coinjection of MLA with leptin also reduced leptin-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) in the hypothalamus. In addition, chronic intracerebroventricular MLA infusion over 14 d via osmotic minipumps significantly increased daily food intake, rate of body weight gain, fat-pad mass, and circulating plasma leptin concentrations. Surprisingly, however, MLA did not antagonize leptin-evoked increases in cytosolic calcium concentrations in vagal afferent neurons in primary culture. Rather, MLA itself produced acute activation selectively in leptin-responsive vagal afferent neurons. These data suggest that MLA is an antagonist for the central effects of leptin on food intake and body weight but an agonist at sites where leptin induces acute neuronal activation. This mixed antagonist/agonist action suggests either 1) that the coupling of a single leptin receptor (ObRb) to acute activation of neurons occurs by a signaling mechanism different from those that mediate centrally evoked reductions in food intake and body weight or 2) that acute neuronal activation and centrally induced reductions of food intake and body weight are mediated by different leptin receptor subtypes.
Authors:
J H Peters; S M Simasko; R C Ritter
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-03-15
Journal Detail:
Title:  Endocrinology     Volume:  148     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-17     Completed Date:  2007-07-24     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2878-85     Citation Subset:  AIM; IM    
Affiliation:
Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, OR 97239, USA. petersj.OHSU@gmail.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Weight / drug effects*
Cells, Cultured
Eating / drug effects*
Infusion Pumps
Leptin / administration & dosage,  analogs & derivatives*,  antagonists & inhibitors*,  pharmacology
Male
Molecular Mimicry
Neurons, Afferent / drug effects*,  metabolism
Rats
Rats, Sprague-Dawley
Recombinant Proteins / administration & dosage,  pharmacology*
Vagus Nerve / drug effects*,  metabolism
Grant Support
ID/Acronym/Agency:
DK 67146/DK/NIDDK NIH HHS; NS 20561/NS/NINDS NIH HHS; R01 DK067146-02/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Leptin; 0/Recombinant Proteins; 0/murine leptin analog
Comments/Corrections

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