From belly to brain: targeting the ghrelin receptor in appetite and food intake regulation

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dc.contributor.authorHowick, Kenneth P.
dc.contributor.authorGriffin, Brendan T.
dc.contributor.authorCryan, John F.
dc.contributor.authorSchellekens, Harriët
dc.date.accessioned2017-01-31T15:52:03Z
dc.date.available2017-01-31T15:52:03Z
dc.date.issued2017-01-27
dc.date.updated2017-01-31T15:44:35Z
dc.description.abstractGhrelin is the only known peripherally-derived orexigenic hormone, increasing appetite and subsequent food intake. The ghrelinergic system has therefore received considerable attention as a therapeutic target to reduce appetite in obesity as well as to stimulate food intake in conditions of anorexia, malnutrition and cachexia. As the therapeutic potential of targeting this hormone becomes clearer, it is apparent that its pleiotropic actions span both the central nervous system and peripheral organs. Despite a wealth of research, a therapeutic compound specifically targeting the ghrelin system for appetite modulation remains elusive although some promising effects on metabolic function are emerging. This is due to many factors, ranging from the complexity of the ghrelin receptor (Growth Hormone Secretagogue Receptor, GHSR-1a) internalisation and heterodimerization, to biased ligand interactions and compensatory neuroendocrine outputs. Not least is the ubiquitous expression of the GHSR-1a, which makes it impossible to modulate centrallymediated appetite regulation without encroaching on the various peripheral functions attributable to ghrelin. It is becoming clear that ghrelin’s central signalling is critical for its effects on appetite, body weight regulation and incentive salience of food. Improving the ability of ghrelin ligands to penetrate the blood brain barrier would enhance central delivery to GHSR-1a expressing brain regions, particularly within the mesolimbic reward circuitry.en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationHowick, K., Griffin, B., Cryan, J. and Schellekens, H. (2017) 'From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation', International Journal of Molecular Sciences, 18(2), 273. doi:10.3390/ijms18020273en
dc.identifier.doi10.3390/ijms18020273
dc.identifier.endpage273-38en
dc.identifier.issn1422-0067
dc.identifier.issued2en
dc.identifier.journaltitleInternational Journal of Molecular Sciencesen
dc.identifier.startpage273-1en
dc.identifier.urihttps://hdl.handle.net/10468/3546
dc.identifier.volume18en
dc.language.isoenen
dc.publisherMDPIen
dc.rights© 2017 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectGhrelinen
dc.subjectDesacyl-ghrelinen
dc.subjectAppetiteen
dc.subjectGHSR-1aen
dc.subjectObesityen
dc.subjectCachexiaen
dc.subjectFood rewarden
dc.subjectMesolimbic reward circuitryen
dc.subjectBlood brain barrieren
dc.titleFrom belly to brain: targeting the ghrelin receptor in appetite and food intake regulationen
dc.typeArticle (peer-reviewed)en
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