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Int. J. Mol. Sci. 2017, 18(2), 273; doi:10.3390/ijms18020273

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

1
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
2
School of Pharmacy, University College Cork, Cork, Ireland
3
Food for Health Ireland, University College Cork, Cork, Ireland
4
Alimentary Pharmabiotic Centre (APC) Microbiome Institute, University College Cork, Cork, Ireland
*
Author to whom correspondence should be addressed.
Academic Editor: Suzanne L. Dickson
Received: 19 December 2016 / Revised: 12 January 2017 / Accepted: 19 January 2017 / Published: 27 January 2017
(This article belongs to the Special Issue Neurobiological Perspectives on Ghrelin)
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Abstract

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 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. View Full-Text
Keywords: ghrelin; desacyl-ghrelin; appetite; GHSR-1a; obesity; cachexia; food reward; mesolimbic reward circuitry; blood brain barrier ghrelin; desacyl-ghrelin; appetite; GHSR-1a; obesity; cachexia; food reward; mesolimbic reward circuitry; blood brain barrier
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Howick, K.; Griffin, B.T.; Cryan, J.F.; Schellekens, H. From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation. Int. J. Mol. Sci. 2017, 18, 273.

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