Cited 5 times in
FoxO1 regulates leptin-induced mood behavior by targeting tyrosine hydroxylase
DC Field | Value | Language |
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dc.contributor.author | 김기우 | - |
dc.contributor.author | 신동민 | - |
dc.contributor.author | 최윤희 | - |
dc.date.accessioned | 2019-03-15T02:25:31Z | - |
dc.date.available | 2019-03-15T02:25:31Z | - |
dc.date.issued | 2019 | - |
dc.identifier.issn | 0026-0495 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/167468 | - |
dc.description.abstract | PURPOSE: While leptin has been associated with various psycho-physiological functions, the molecular network in leptin-mediated mood regulation remains elusive. METHODS: Anxiolytic behaviors and tyrosine hydroxylase (TH) levels were examined after leptin administration. Functional roles of STAT3 and FoxO1 in regulation of TH expression were investigated using in vivo and in vitro systems. A series of animal behavioral tests using dopaminergic neuron-specific FoxO1 KO (FoxO1 KODAT) were performed and investigated the roles of FoxO1 in regulation of mood behaviors. RESULTS: Here, we show that administration of leptin induces anxiolytic-like phenotype through the activation of signal transducer and activator of transcription 3 (STAT3) and the inhibition of forkhead box protein O1 (FoxO1) in dopaminergic (DA) neurons of the midbrain. Specifically, STAT3 and FoxO1 directly bind to and exert opposing effects on tyrosine hydroxylase (TH) expression, where STAT3 acts as an enhancer and FoxO1 acts as a prominent repressor. Accordingly, suppression of the prominent suppressor FoxO1 by leptin strongly increased TH expression. Furthermore, our previous results showed that specific deletion of FoxO1 in DA neurons (FoxO1 KODAT) led to a profound elevation of TH activity and dopamine contents. Finally, FoxO1 KODAT mice exhibited enhanced leptin sensitivity as well as displayed reduced anxiety- and depression-like behaviors. CONCLUSIONS: This work establishes a novel molecular mechanism of mood behavior regulation by leptin and suggests FoxO1 suppression by leptin might be a key for leptin-induced behavioral manifestation in DA neurons. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | W.B. Saunders | - |
dc.relation.isPartOf | METABOLISM-CLINICAL AND EXPERIMENTAL | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | FoxO1 regulates leptin-induced mood behavior by targeting tyrosine hydroxylase | - |
dc.type | Article | - |
dc.contributor.college | College of Dentistry (치과대학) | - |
dc.contributor.department | Dept. of Oral Biology (구강생물학교실) | - |
dc.contributor.googleauthor | Dong Hwee Son | - |
dc.contributor.googleauthor | Khanh V. Doan | - |
dc.contributor.googleauthor | Dong Joo Yang | - |
dc.contributor.googleauthor | Ji Su Sun | - |
dc.contributor.googleauthor | Seul Ki Kim | - |
dc.contributor.googleauthor | Namju Kang | - |
dc.contributor.googleauthor | Jung Yun Kang | - |
dc.contributor.googleauthor | Ji-Hye Paik | - |
dc.contributor.googleauthor | Ronald A. DePinho | - |
dc.contributor.googleauthor | Yun-Hee Choi | - |
dc.contributor.googleauthor | Dong Min Shin | - |
dc.contributor.googleauthor | Ki Woo Kim | - |
dc.identifier.doi | 10.1016/j.metabol.2018.11.013 | - |
dc.contributor.localId | A05301 | - |
dc.contributor.localId | A02091 | - |
dc.contributor.localId | A04144 | - |
dc.relation.journalcode | J02223 | - |
dc.identifier.eissn | 1532-8600 | - |
dc.identifier.pmid | 30500562 | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S002604951830252X | - |
dc.subject.keyword | Anxiolytic | - |
dc.subject.keyword | Dopaminergic neuron | - |
dc.subject.keyword | Forkhead transcriptional factor O1 | - |
dc.subject.keyword | Leptin | - |
dc.subject.keyword | Midbrain | - |
dc.subject.keyword | Signal transducer and activator of transcription 3 | - |
dc.subject.keyword | Tyrosine hydroxylase | - |
dc.contributor.alternativeName | kim, KiWoo | - |
dc.contributor.affiliatedAuthor | 김기우 | - |
dc.contributor.affiliatedAuthor | 신동민 | - |
dc.contributor.affiliatedAuthor | 최윤희 | - |
dc.citation.volume | 91 | - |
dc.citation.startPage | 43 | - |
dc.citation.endPage | 52 | - |
dc.identifier.bibliographicCitation | METABOLISM-CLINICAL AND EXPERIMENTAL, Vol.91 : 43-52, 2019 | - |
dc.identifier.rimsid | 48807 | - |
dc.type.rims | ART | - |
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