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From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation

Ghrelin 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...

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Autores principales: Howick, Ken, Griffin, Brendan T., Cryan, John F., Schellekens, Harriët
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343809/
https://www.ncbi.nlm.nih.gov/pubmed/28134808
http://dx.doi.org/10.3390/ijms18020273
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author Howick, Ken
Griffin, Brendan T.
Cryan, John F.
Schellekens, Harriët
author_facet Howick, Ken
Griffin, Brendan T.
Cryan, John F.
Schellekens, Harriët
author_sort Howick, Ken
collection PubMed
description Ghrelin 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 centrally-mediated 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.
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spelling pubmed-53438092017-03-16 From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation Howick, Ken Griffin, Brendan T. Cryan, John F. Schellekens, Harriët Int J Mol Sci Review Ghrelin 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 centrally-mediated 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. MDPI 2017-01-27 /pmc/articles/PMC5343809/ /pubmed/28134808 http://dx.doi.org/10.3390/ijms18020273 Text en © 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/).
spellingShingle Review
Howick, Ken
Griffin, Brendan T.
Cryan, John F.
Schellekens, Harriët
From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation
title From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation
title_full From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation
title_fullStr From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation
title_full_unstemmed From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation
title_short From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation
title_sort from belly to brain: targeting the ghrelin receptor in appetite and food intake regulation
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343809/
https://www.ncbi.nlm.nih.gov/pubmed/28134808
http://dx.doi.org/10.3390/ijms18020273
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