Document Detail


EGR1 Is a target for cooperative interactions between cholecystokinin and leptin, and inhibition by ghrelin, in vagal afferent neurons.
MedLine Citation:
PMID:  20534729     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Food intake is regulated by signals from peripheral organs, but the way these are integrated remains uncertain. Cholecystokinin (CCK) from the intestine and leptin from adipocytes interact to inhibit food intake. Our aim was to examine the hypothesis that these interactions occur at the level of vagal afferent neurons via control of the immediate early gene EGR1. We now report that CCK stimulates redistribution to the nucleus of early growth response factor-1 (EGR1) in these neurons in vivo and in culture, and these effects are not dependent on EGR1 synthesis. Leptin stimulates EGR1 expression; leptin alone does not stimulate nuclear translocation, but it strongly potentiates the action of CCK. Ghrelin inhibits CCK-stimulated nuclear translocation of EGR1 and leptin-stimulated EGR1 expression. Expression of the gene encoding the satiety peptide cocaine- and amphetamine-regulated transcript (CARTp) is stimulated by CCK via an EGR1-dependent mechanism, and this is strongly potentiated by leptin. Leptin potentiated inhibition of food intake by endogenous CCK in the rat in conditions reflecting changes in EGR1 activation. The data indicate that by separately regulating EGR1 activation and synthesis, CCK and leptin interact cooperatively to define the capacity for satiety signaling by vagal afferent neurons; manipulation of these interactions may be therapeutically beneficial.
Authors:
Guillaume de Lartigue; Gyorgy Lur; Rod Dimaline; Andrea Varro; Helen Raybould; Graham J Dockray
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-06-09
Journal Detail:
Title:  Endocrinology     Volume:  151     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-27     Completed Date:  2010-09-08     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3589-99     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Appetite Regulation / drug effects,  genetics
Cell Nucleus / drug effects,  metabolism
Cells, Cultured
Cholecystokinin / metabolism,  pharmacology*,  physiology
Down-Regulation / drug effects
Drug Antagonism
Drug Synergism
Early Growth Response Protein 1 / genetics*,  metabolism,  physiology
Ghrelin / metabolism,  pharmacology,  physiology*
Leptin / metabolism,  pharmacology*,  physiology
Male
Neurons, Afferent / drug effects*,  metabolism
Protein Transport / drug effects
Rats
Rats, Wistar
Transcriptional Activation / drug effects
Vagus Nerve / drug effects*,  metabolism
Grant Support
ID/Acronym/Agency:
G8714277//Medical Research Council; R01 DK041004/DK/NIDDK NIH HHS; R01 DK041004-22/DK/NIDDK NIH HHS; //Biotechnology and Biological Sciences Research Council; //Medical Research Council
Chemical
Reg. No./Substance:
0/Early Growth Response Protein 1; 0/Egr1 protein, mouse; 0/Ghrelin; 0/Leptin; 9011-97-6/Cholecystokinin
Comments/Corrections

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