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Review
. 2017 Apr 11;18(4):798.
doi: 10.3390/ijms18040798.

Therapeutic Potential of Targeting the Ghrelin Pathway

Gustav Colldén  1 , Matthias H Tschöp  2   3 , Timo D Müller  4   5
Affiliations
Review

Therapeutic Potential of Targeting the Ghrelin Pathway

Gustav Colldén et al. Int J Mol Sci. .

Abstract

Ghrelin was discovered in 1999 as the endogenous ligand of the growth-hormone secretagogue receptor 1a (GHSR1a). Since then, ghrelin has been found to exert a plethora of physiological effects that go far beyond its initial characterization as a growth hormone (GH) secretagogue. Among the numerous well-established effects of ghrelin are the stimulation of appetite and lipid accumulation, the modulation of immunity and inflammation, the stimulation of gastric motility, the improvement of cardiac performance, the modulation of stress, anxiety, taste sensation and reward-seeking behavior, as well as the regulation of glucose metabolism and thermogenesis. Due to a variety of beneficial effects on systems' metabolism, pharmacological targeting of the endogenous ghrelin system is widely considered a valuable approach to treat metabolic complications, such as chronic inflammation, gastroparesis or cancer-associated anorexia and cachexia. The aim of this review is to discuss and highlight the broad pharmacological potential of ghrelin pathway modulation for the treatment of anorexia, cachexia, sarcopenia, cardiopathy, neurodegenerative disorders, renal and pulmonary disease, gastrointestinal (GI) disorders, inflammatory disorders and metabolic syndrome.

Keywords: anorexia; ghrelin; inflammation; pathology; therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Physiological actions of ghrelin: schematic illustrating the various hormonal actions of ghrelin in different target organs. ACTH, adrenocorticotropic hormone. GH, growth hormone. IGF-1, insulin-like growth factor 1. Up/down arrows denote increase/decrease.
Figure 2
Figure 2
Intracellular processing of ghrelin: schematic illustrating the intracellular processing of ghrelin. The 117-aminoacid precursor peptide preproghrelin is cleaved to proghrelin, which is in turn cleaved by prohormone convertase 1/3 to the mature 28-amino acid ghrelin peptide. Prior to secretion, des-acyl ghrelin is acylated by the hormone ghrelin-O-acyltransferase (GOAT), which permits its binding to the growth-hormone secretagogue receptor 1a (GHSR1a). AG, acyl ghrelin. DAG, des-acyl ghrelin.
Figure 3
Figure 3
Avenues for ghrelin therapy: schematic of the various pathological conditions for which there is at least preclinical evidence suggesting potential therapeutic benefit of ghrelin treatment.
See this image and copyright information in PMC

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