An overview of ghrelin<i>O</i>-acyltransferase inhibitors: a literature and patent review for 2010-2019

Moose, Jacob E.; Leets, Katelyn A.; Mate, Nilamber A.; Chisholm, John D.; Hougland, James L.

doi:10.1080/13543776.2020.1776263

Cited by 20 publications

(18 citation statements)

References 155 publications

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“…Despite the role of the ghrelin system in stress-related psychiatric disorders is not fully resolved yet, it provides a new and interesting vantage point in the search for more efficient diagnostic and therapeutic strategies (also see Figure 1). It remains unknown whether a modulation of the ghrelin system could be beneficial in the treatment of stress-related psychiatric disorders, however multiple pharmacological tools to do so have become available over the last two decades (McGovern et al, 2016;Lee et al, 2020;Moose et al, 2020). This includes GHSR agonists and antagonists as well as inverse agonists and GOAT inhibitors, although no authorized medicine is commercially available to date.…”

Section: Therapeutic Potential Of Targeting the Ghrelin System In Strmentioning

confidence: 99%

The Good, the Bad and the Unknown Aspects of Ghrelin in Stress Coping and Stress-Related Psychiatric Disorders

Fritz

Singewald

Bundel

2020

Front. Synaptic Neurosci.

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Ghrelin is a peptide hormone released by specialized X/A cells in the stomach and activated by acylation. Following its secretion, it binds to ghrelin receptors in the periphery to regulate energy balance, but it also acts on the central nervous system where it induces a potent orexigenic effect. Several types of stressors have been shown to stimulate ghrelin release in rodents, including nutritional stressors like food deprivation, but also physical and psychological stressors such as foot shocks, social defeat, forced immobilization or chronic unpredictable mild stress. The mechanism through which these stressors drive ghrelin release from the stomach lining remains unknown and, to date, the resulting consequences of ghrelin release for stress coping remain poorly understood. Indeed, ghrelin has been proposed to act as a stress hormone that reduces fear, anxiety-and depression-like behaviors in rodents but some studies suggest that ghrelin may-in contrast-promote such behaviors. In this review, we aim to provide a comprehensive overview of the literature on the role of the ghrelin system in stress coping. We discuss whether ghrelin release is more than a byproduct of disrupted energy homeostasis following stress exposure. Furthermore, we explore the notion that ghrelin receptor signaling in the brain may have effects independent of circulating ghrelin and in what way this might influence stress coping in rodents. Finally, we examine how the ghrelin system could be utilized as a therapeutic avenue in stressrelated psychiatric disorders (with a focus on anxiety-and trauma-related disorders), for example to develop novel biomarkers for a better diagnosis or new interventions to tackle relapse or treatment resistance in patients.

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Section: Therapeutic Potential Of Targeting the Ghrelin System In Strmentioning

confidence: 99%

The Good, the Bad and the Unknown Aspects of Ghrelin in Stress Coping and Stress-Related Psychiatric Disorders

Fritz

Singewald

Bundel

2020

Front. Synaptic Neurosci.

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“…Additional data from longitudinal studies with larger samples could highlight specific patterns and associations of this hormone with psychopathology and behaviors during the course of treatment and recovery, eventually supporting the use of ghrelin assessment in clinical practice for a better characterization of EDs. Finally, targeted pharmacological interventions could be used in patients with a history of childhood trauma, such as ghrelin O‐acyltransferase inhibitors (Moose et al., 2020), to modulate reward circuits and reduce pathological behaviors.…”

Section: Discussionmentioning

confidence: 99%

Ghrelin as a possible biomarker and maintaining factor in patients with eating disorders reporting childhood traumatic experiences

Rossi

Cassioli

Gironi

et al. 2021

Euro Eating Disorders Rev

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Objective The recent conceptualization of ghrelin as a stress hormone suggested that its chronic alterations may have a role in maintaining overeating behaviors in subjects with eating disorders (EDs) reporting childhood traumatic experiences. The aim of this study was to investigate the alterations of ghrelin levels in patients with EDs, their associations with early trauma, binge and emotional eating, and possible moderation/mediation models. Method Sixty‐four patients with EDs and 42 healthy controls (HCs) had their plasma ghrelin levels measured and completed questionnaires evaluating general and ED‐specific psychopathology, emotional eating, and childhood traumatic experiences. Results Participants with anorexia nervosa had higher ghrelin levels than HCs in body mass index (BMI)‐adjusted comparisons. Moreover, patients reporting a history of childhood trauma had higher ghrelin levels. Childhood sexual abuse (CSA), BMI, and self‐induced vomiting were independent predictors of ghrelin levels. Moderation analyses showed that ghrelin levels were associated with binge and emotional eating only for higher levels of childhood trauma. Elevated ghrelin was a significant mediator for the association of CSA with binge eating. Conclusions These results support the hypothesis that chronic alterations in ghrelin levels following childhood traumatic experiences could represent a neurobiological maintaining factor of pathological overeating behaviors in EDs.

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“…Next, the ghrelin O-acyltransferase (GOAT) enzyme acylates or, more specifically, octanoylates proghrelin at the serine-3 residue, and the mature, 28-amino acid ghrelin is secreted [ 43 ]. Acyl ghrelin (AG) and desacyl ghrelin (DAG) can both be found in the blood stream, but only AG is capable of high-affinity binding to the growth hormone secretagogue receptor (GHSR) [ 49 , 50 ].…”

Section: Ghrelin and The Ghrelin Receptormentioning

confidence: 99%

Gut peptides and the microbiome: focus on ghrelin

Leeuwendaal

Cryan²,

Schellekens

2021

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of review In this review, we present recent insights into the role of the gut microbiota on gastrointestinal (GI) peptide secretion and signalling, with a focus on the orexigenic hormone, ghrelin. Recent findings Evidence is accumulating suggesting that secretion of GI peptides is modulated by commensal bacteria present in our GI tract. Recent data shows that the gut microbiome impacts on ghrelinergic signalling through its metabolites, at the level of the ghrelin receptor (growth hormone secretagogue receptor) and highlights concomitant changes in circulating ghrelin levels with specific gut microbiota changes. However, the mechanisms by which the gut microbiota interacts with gut peptide secretion and signalling, including ghrelin, are still largely unknown. Summary The gut microbiota may directly or indirectly influence secretion of the orexigenic hormone, ghrelin, similar to the modulation of satiety inducing GI hormones. Although data demonstrating a role of the microbiota on ghrelinergic signalling is starting to emerge, future mechanistic studies are needed to understand the full impact of the microbiota-ghrelin axis on metabolism and central-regulated homeostatic and non-homeostatic controls of food intake.

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An overview of ghrelinO-acyltransferase inhibitors: a literature and patent review for 2010-2019

Cited by 20 publications

References 155 publications

The Good, the Bad and the Unknown Aspects of Ghrelin in Stress Coping and Stress-Related Psychiatric Disorders

The Good, the Bad and the Unknown Aspects of Ghrelin in Stress Coping and Stress-Related Psychiatric Disorders

Ghrelin as a possible biomarker and maintaining factor in patients with eating disorders reporting childhood traumatic experiences

Gut peptides and the microbiome: focus on ghrelin

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