Unacylated Ghrelin: A Gut-Limb Connection

Chakrabarti, Subrata

doi:10.2337/db14-1825

Cited by 2 publications

(4 citation statements)

References 13 publications

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“…In glucose-intolerant mice, des-acyl ghrelin provides a protective effect on skeletal muscle and endothelial cells that are subjected to ischaemia conditions [ 73 ]. Des-acyl ghrelin treatment also led to the prevention of cellular damage through activation of endothelial oxidative defense [ 69 ]. In another study, incubation of human differentiating omental adipocytes with des-acyl ghrelin impeded TNF-α-induced activation of caspase-8 and caspase-3 leading to a reduction in apoptosis.…”

Section: Role Of Acylation In Ghrelin Signallingmentioning

confidence: 99%

“…As a result, the unacylated form of ghrelin (des-acyl ghrelin) was thought to be a nonfunctional peptide [65][66][67]. However, des-acyl ghrelin has been shown to modulate a range of physiological processes, both independently of and in opposition to acyl ghrelin [68,69]. For example, treatment with either des-acyl ghrelin or ghrelin can stimulate insulin release in β-cell lines [70,71].…”

Section: Biological Signalling By Des-acyl Ghrelinmentioning

confidence: 99%

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Ghrelin octanoylation by ghrelin O -acyltransferase: protein acylation impacting metabolic and neuroendocrine signalling

et al. 2021

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The acylated peptide hormone ghrelin impacts a wide range of physiological processes but is most well known for controlling hunger and metabolic regulation. Ghrelin requires a unique posttranslational modification, serine octanoylation, to bind and activate signalling through its cognate GHS-R1a receptor. Ghrelin acylation is catalysed by ghrelin O -acyltransferase (GOAT), a member of the membrane-bound O -acyltransferase (MBOAT) enzyme family. The ghrelin/GOAT/GHS-R1a system is defined by multiple unique aspects within both protein biochemistry and endocrinology. Ghrelin serves as the only substrate for GOAT within the human proteome and, among the multiple hormones involved in energy homeostasis and metabolism such as insulin and leptin, acts as the only known hormone in circulation that directly stimulates appetite and hunger signalling. Advances in GOAT enzymology, structural modelling and inhibitor development have revolutionized our understanding of this enzyme and offered new tools for investigating ghrelin signalling at the molecular and organismal levels. In this review, we briefly summarize the current state of knowledge regarding ghrelin signalling and ghrelin/GOAT enzymology, discuss the GOAT structural model in the context of recently reported MBOAT enzyme superfamily member structures, and highlight the growing complement of GOAT inhibitors that offer options for both ghrelin signalling studies and therapeutic applications.

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Section: Role Of Acylation In Ghrelin Signallingmentioning

confidence: 99%

Section: Biological Signalling By Des-acyl Ghrelinmentioning

confidence: 99%

Ghrelin octanoylation by ghrelin O -acyltransferase: protein acylation impacting metabolic and neuroendocrine signalling

et al. 2021

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“…The pathological events which lead to the presentation of CLI are multifactorial, complex, and beyond the scope of this review [reviewed in Ref. ( 24 )]. The underlying pathological events leading to CLI are macro- and microvascular circulation defects, resulting in diminished arterial perfusion.…”

Section: Pathophysiology Of CLImentioning

confidence: 99%

“…The 28-amino acid peptide hormone ghrelin, first discovered in 1999 as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R) ( 21 ), has recently been proposed as a novel therapeutic for CLI ( 22 – 24 ). The GHS-R is a G-protein coupled receptor, ubiquitous throughout the cardiovascular and autonomic nervous systems ( 25 , 26 ), which plausibly accounts for the diverse range of effects ghrelin has on cardiovascular function ( 25 , 26 ).…”

Section: Introductionmentioning

confidence: 99%

Ghrelin, MicroRNAs, and Critical Limb Ischemia: Hungering for a Novel Treatment Option

et al. 2017

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Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease. It is characterized by chronic pain at rest, skin ulcerations, and gangrene tissue loss. CLI is a highly morbid condition, resulting in a severely diminished quality of life and a significant risk of mortality. The primary goal of therapy for CLI is to restore blood flow to the affected limb, which is only possible by surgery, but is inadvisable in up to 50% of patients. This subset of patients who are not candidates for revascularisation are referred to as “no-option” patients and are the focus of investigation for novel therapeutic strategies. Angiogenesis, arteriogenesis and vasculogenesis are the processes whereby new blood vessel networks form from the pre-existing vasculature and primordial cells, respectively. In therapeutic angiogenesis, exogenous stimulants are administered to promote angiogenesis and augment limb perfusion, offering a potential treatment option for “no option” patients. However, to date, very few clinical trials of therapeutic angiogenesis in patients with CLI have reported clinically significant results, and it remains a major challenge. Ghrelin, a 28-amino acid peptide, is emerging as a potential novel therapeutic for CLI. In pre-clinical models, exogenous ghrelin has been shown to induce therapeutic angiogenesis, promote muscle regeneration, and reduce oxidative stress via the modulation of microRNAs (miRs). miRs are endogenous, small, non-coding ribonucleic acids of ~20–22 nucleotides which regulate gene expression at the post-transcriptional level by either translational inhibition or by messenger ribonucleic acid cleavage. This review focuses on the mounting evidence for the use of ghrelin as a novel therapeutic for CLI, and highlights the miRs which orchestrate these physiological events.

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Unacylated Ghrelin: A Gut-Limb Connection

Cited by 2 publications

References 13 publications

Ghrelin octanoylation by ghrelin O -acyltransferase: protein acylation impacting metabolic and neuroendocrine signalling

Ghrelin octanoylation by ghrelin O -acyltransferase: protein acylation impacting metabolic and neuroendocrine signalling

Ghrelin, MicroRNAs, and Critical Limb Ischemia: Hungering for a Novel Treatment Option

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