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Role of hypothalamic Foxo1 in the regulation of food intake and energy homeostasis

Cited 218 time in Web of Science Cited 239 time in Scopus
Authors
Kim, Min-Seon; Pak, Youngmi; Jang, Pil-Geum; Namkoong, Cherl; Choi, Yon-Sik; Won, Jong-Chul; Kim, Kyung-Sup; Kim, Seung-Whan; Kim, Hyo-Soo; Park, Joong-Yeol; Kim, Young-Bum; Lee, Ki-Up
Issue Date
2006-06-20
Publisher
Nature Publishing Group
Citation
Nat Neurosci. 2006 Jul;9(7):901-6. Epub 2006 Jun 18.
Keywords
Analysis of VarianceAnimalsBlotting, Western/methodsBody Weight/drug effects/physiologyCell Line, TumorChromatin Immunoprecipitation/methodsEating/drug effects/*physiologyElectrophoretic Mobility Shift Assay/methodsEnergy Metabolism/drug effects/*physiologyForkhead Transcription Factors/*physiologyGene Expression/drug effects/physiologyGreen Fluorescent Proteins/metabolismHomeostasis/drug effects/*physiologyHumansHypothalamus/drug effects/*metabolismImmunohistochemistry/methodsInsulin/pharmacologyLeptin/pharmacologyMaleMiceMice, Inbred C57BLNeuroblastomaRNA, Small Interfering/pharmacology
Abstract
Insulin signaling in the hypothalamus plays a role in maintaining body weight. Studies suggest that the forkhead transcription factor Foxo1 is an important mediator of insulin signaling in peripheral tissues. Here we demonstrate that in normal mice, hypothalamic Foxo1 expression is reduced by the anorexigenic hormones insulin and leptin. These hormones' effects on feeding are inhibited when hypothalamic Foxo1 is activated, establishing a new signaling pathway through which insulin and leptin regulate food intake in hypothalamic neurons. Moreover, activation of Foxo1 in the hypothalamus increases food intake and body weight, whereas inhibition of Foxo1 decreases both. Foxo1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti-related protein through the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway, but suppresses the transcription of anorexigenic proopiomelanocortin by antagonizing the activity of signal transducer-activated transcript-3 (STAT3). Our data suggest that hypothalamic Foxo1 is an important regulator of food intake and energy balance.
ISSN
1097-6256 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16783365

https://hdl.handle.net/10371/42982
DOI
https://doi.org/10.1038/nn1731
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College of Medicine/School of Medicine (의과대학/대학원)Molecular and Genomic Medicine (분자유전체의학전공)Journal Papers (저널논문_분자유전체의학전공)
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