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

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dc.contributor.author Schellekens, Harriët
dc.contributor.author Clarke, Gerard
dc.contributor.author Jeffery, Ian B.
dc.contributor.author Dinan, Timothy G.
dc.contributor.author Cryan, John F.
dc.contributor.editor Bartolomucci, Alessandro
dc.date.accessioned 2012-12-12T10:29:02Z
dc.date.available 2012-12-12T10:29:02Z
dc.date.copyright 2012
dc.date.issued 2012-03-20
dc.identifier.citation Schellekens 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.0032266 en
dc.identifier.volume 7 en
dc.identifier.issued 3 en
dc.identifier.startpage e32266 en
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10468/844
dc.identifier.doi 10.1371/journal.pone.0032266
dc.description.abstract The 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.sponsorship Science Foundation Ireland (SFI-CSET); Science Foundation Ireland (02/CE/B124); Science Foundation Ireland (07/CE/B1368); Enterprise Ireland (CC20080001); European Commission (FP7/2007–2013, Grant Agreement 201714) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher PLOS en
dc.relation.uri http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0032266
dc.rights 2012 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.uri http://creativecommons.org/licenses/by/2.5/ en
dc.subject Receptor editing en
dc.subject Obesity en
dc.subject Serotonin receptors en
dc.subject Appetite control en
dc.subject Anorectic en
dc.title Dynamic 5-HT2C receptor editing in a mouse model of obesity en
dc.type Article (peer-reviewed) en
dc.internal.authorurl http://publish.ucc.ie/researchprofiles/C003/jcryan en
dc.internal.authorcontactother Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland. Email: J.Cryan@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.rssid 133793730
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Enterprise Ireland en
dc.contributor.funder European Commission en
dc.contributor.funder American Neurogastroenterology and Motility Society en
dc.description.status Peer reviewed en
dc.identifier.journaltitle PLoS ONE en
dc.internal.copyrightchecked Sherpa Romeo Green Journal. Policy: The Public Library of Science (PLOS) applies the Creative Commons Attribution License (CC-BY) to works we publish (read the human-readable summary or the full license legal code). Under this license, authors retain ownership of the copyright for their content, but allow anyone to download, reuse, reprint, modify, distribute, and/or copy the content as long as the original authors and source are cited. No permission is required from the authors or the publishers. Appropriate attribution can be provided by simply citing the original article (e.g., Kaltenbach LS et al. (2007) Huntingtin Interacting Proteins Are Genetic Modifiers of Neurodegeneration. PLOS Genet 3(5): e82. doi:10.1371/journal.pgen.0030082). en
dc.internal.IRISemailaddress j.cryan@ucc.ie en


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2012 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. Except where otherwise noted, this item's license is described as 2012 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.
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