Dynamic 5-HT2C receptor editing in a mouse model of obesity

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dc.contributor.authorSchellekens, Harriƫt
dc.contributor.authorClarke, Gerard
dc.contributor.authorJeffery, Ian B.
dc.contributor.authorDinan, Timothy G.
dc.contributor.authorCryan, John F.
dc.contributor.editorBartolomucci, Alessandro
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderEnterprise Irelanden
dc.contributor.funderEuropean Commissionen
dc.contributor.funderAmerican Neurogastroenterology and Motility Societyen
dc.date.accessioned2012-12-12T10:29:02Z
dc.date.available2012-12-12T10:29:02Z
dc.date.copyright2012
dc.date.issued2012-03-20
dc.description.abstractThe central serotonergic signalling system has been shown to play an important role in appetite control and the regulation of food intake. Serotonin exerts its anorectic effects mainly through the 5-HT1B, 5-HT2C and 5-HT6 receptors and these are therefore receiving increasing attention as principal pharmacotherapeutic targets for the treatment of obesity. The 5-HT2C receptor has the distinctive ability to be modified by posttranscriptional RNA editing on 5 nucleotide positions (A, B, C, D, E), having an overall decreased receptor function. Recently, it has been shown that feeding behaviour and fat mass are altered when the 5-HT2C receptor RNA is fully edited, suggesting a potential role for 5-HT2C editing in obesity. The present studies investigate the expression of serotonin receptors involved in central regulation of food intake, appetite and energy expenditure, with particular focus on the level of 5-HT2C receptor editing. Using a leptin-deficient mouse model of obesity (ob/ob), we show increased hypothalamic 5-HT1A receptor expression as well as increased hippocampal 5-HT1A, 5-HT1B, and 5-HT6 receptor mRNA expression in obese mice compared to lean control mice. An increase in full-length 5-HT2C expression, depending on time of day, as well as differences in 5-HT2C receptor editing were found, independent of changes in total 5-HT2C receptor mRNA expression. This suggests that a dynamic regulation exists of the appetite-suppressing effects of the 5-HT2C receptor in both the hypothalamus and the hippocampus in the ob/ob mice model of obesity. The differential 5-HT1A, 5-HT1B and 5-HT6 receptor expression and altered 5-HT2C receptor editing profile reported here is poised to have important consequences for the development of novel anti-obesity therapies.en
dc.description.sponsorshipScience Foundation Ireland (SFI-CSET); Science Foundation Ireland (02/CE/B124); Science Foundation Ireland (07/CE/B1368); Enterprise Ireland (CC20080001); European Commission (FP7/2007ā€“2013, Grant Agreement 201714)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationSchellekens H, Clarke G, Jeffery IB, Dinan TG, Cryan JF (2012) Dynamic 5-HT2C Receptor Editing in a Mouse Model of Obesity. PLoS ONE 7(3): e32266. doi:10.1371/journal.pone.0032266en
dc.identifier.doi10.1371/journal.pone.0032266
dc.identifier.issn1932-6203
dc.identifier.issued3en
dc.identifier.journaltitlePLoS ONEen
dc.identifier.startpagee32266en
dc.identifier.urihttps://hdl.handle.net/10468/844
dc.identifier.volume7en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urihttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0032266
dc.rights2012 Schellekens et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permit unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/en
dc.subjectReceptor editingen
dc.subjectObesityen
dc.subjectSerotonin receptorsen
dc.subjectAppetite controlen
dc.subjectAnorecticen
dc.titleDynamic 5-HT2C receptor editing in a mouse model of obesityen
dc.typeArticle (peer-reviewed)en
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