Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis

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dc.contributor.authorBerglund, Eric Dko
dc.contributor.authorLiu, Chenko
dc.contributor.authorSohn, Jong Wooko
dc.contributor.authorLiu, Tieminko
dc.contributor.authorKim, Mi Hwako
dc.contributor.authorLee, Charlotte Eko
dc.contributor.authorVianna, Claudia Rko
dc.contributor.authorWilliams, Kevin Wko
dc.contributor.authorXu, Yongko
dc.contributor.authorElmquist, Joel Kko
dc.date.accessioned2015-01-27T02:24:16Z-
dc.date.available2015-01-27T02:24:16Z-
dc.date.created2014-11-25-
dc.date.created2014-11-25-
dc.date.issued2013-12-
dc.identifier.citationJOURNAL OF CLINICAL INVESTIGATION, v.123, no.12, pp.5061 - 5070-
dc.identifier.issn0021-9738-
dc.identifier.urihttp://hdl.handle.net/10203/193113-
dc.description.abstractEnergy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor agonists on energy and glucose homeostasis are unknown. Here, we show that mice lacking serotonin 2C receptors (Htr2c) specifically in pro-opiomelanocortin (POMC) neurons had normal body weight but developed glucoregulatory defects including hyperinsulinemia, hyperglucagonemia, hyperglycemia, and insulin resistance. Moreover, these mice did not show anorectic responses to serotonergic agents that suppress appetite and developed hyperphagia and obesity when they were fed a high-fat/high-sugar diet. A requirement of serotonin 2C receptors in POMC neurons for the maintenance of normal energy and glucose homeostasis was further demonstrated when Htr2c loss was induced in POMC neurons in adult mice using a tamoydfen-inducible POMC-cre system. These data demonstrate that serotonin 2C receptor-expressing POMC neurons are required to control energy and glucose homeostasis and implicate POMC neurons as the target for the effect of serotonin 2C receptor agonists on weight-loss induction and improved glycemic control.-
dc.languageEnglish-
dc.publisherAMER SOC CLINICAL INVESTIGATION INC-
dc.subjectHEPATIC INSULIN SENSITIVITY-
dc.subjectD-FENFLURAMINE-
dc.subjectLEPTIN ACTION-
dc.subjectPOMC NEURONS-
dc.subjectMICE-
dc.subjectACTIVATION-
dc.subjectGLUCAGON-
dc.subjectSYSTEM-
dc.subjectDRUGS-
dc.subjectHYPOTHALAMUS-
dc.titleSerotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis-
dc.typeArticle-
dc.identifier.wosid000327826100014-
dc.identifier.scopusid2-s2.0-84890109255-
dc.type.rimsART-
dc.citation.volume123-
dc.citation.issue12-
dc.citation.beginningpage5061-
dc.citation.endingpage5070-
dc.citation.publicationnameJOURNAL OF CLINICAL INVESTIGATION-
dc.identifier.doi10.1172/JCI70338-
dc.contributor.localauthorSohn, Jong Woo-
dc.contributor.nonIdAuthorBerglund, Eric D-
dc.contributor.nonIdAuthorLiu, Chen-
dc.contributor.nonIdAuthorLiu, Tiemin-
dc.contributor.nonIdAuthorKim, Mi Hwa-
dc.contributor.nonIdAuthorLee, Charlotte E-
dc.contributor.nonIdAuthorVianna, Claudia R-
dc.contributor.nonIdAuthorWilliams, Kevin W-
dc.contributor.nonIdAuthorXu, Yong-
dc.contributor.nonIdAuthorElmquist, Joel K-
dc.type.journalArticleArticle-
dc.subject.keywordPlusHEPATIC INSULIN SENSITIVITY-
dc.subject.keywordPlusD-FENFLURAMINE-
dc.subject.keywordPlusLEPTIN ACTION-
dc.subject.keywordPlusPOMC NEURONS-
dc.subject.keywordPlusMICE-
dc.subject.keywordPlusACTIVATION-
dc.subject.keywordPlusGLUCAGON-
dc.subject.keywordPlusSYSTEM-
dc.subject.keywordPlusDRUGS-
dc.subject.keywordPlusHYPOTHALAMUS-
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