Ghrelin Receptor Mutations and Human Obesity

Wang, W.; Tao, Ya-Xiong

doi:10.1016/bs.pmbts.2016.02.001

Cited by 19 publications

(6 citation statements)

References 78 publications

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“…Human genetic studies have identified that rare mutations and single-nucleotide polymorphisms of GHSR gene might be associated with obesity. 598 In circulation, esterases can remove the octanoyl group of acylated ghrelin and switch it to unacylated ghrelin. Intriguingly, membrane-anchored GOAT can reacylate unacylated ghrelin to acylated one, which can still function through GHS-R1a signaling.…”

Section: Drugs/compounds For the Treatment Of Obesitymentioning

confidence: 99%

Signaling pathways in obesity: mechanisms and therapeutic interventions

Wen

Zhang

et al. 2022

Sig Transduct Target Ther

182

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Obesity is a complex, chronic disease and global public health challenge. Characterized by excessive fat accumulation in the body, obesity sharply increases the risk of several diseases, such as type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease, and is linked to lower life expectancy. Although lifestyle intervention (diet and exercise) has remarkable effects on weight management, achieving long-term success at weight loss is extremely challenging, and the prevalence of obesity continues to rise worldwide. Over the past decades, the pathophysiology of obesity has been extensively investigated, and an increasing number of signal transduction pathways have been implicated in obesity, making it possible to fight obesity in a more effective and precise way. In this review, we summarize recent advances in the pathogenesis of obesity from both experimental and clinical studies, focusing on signaling pathways and their roles in the regulation of food intake, glucose homeostasis, adipogenesis, thermogenesis, and chronic inflammation. We also discuss the current anti-obesity drugs, as well as weight loss compounds in clinical trials, that target these signals. The evolving knowledge of signaling transduction may shed light on the future direction of obesity research, as we move into a new era of precision medicine.

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Section: Drugs/compounds For the Treatment Of Obesitymentioning

confidence: 99%

Signaling pathways in obesity: mechanisms and therapeutic interventions

Wen

Zhang

et al. 2022

Sig Transduct Target Ther

182

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“…This high level of basal activity may serve as a “signaling set point” to counterbalance the inhibitory input from leptin and insulin in appetite regulation 12 . Several naturally occurring mutations of ghrelin receptor , such as A204E and F279L, decrease the basal activity of the receptor and have been found to associate with obesity, diabetes, and short stature 14 , which led to the idea of ghrelin receptor being an attractive therapeutic target for these diseases. However, there are only two orally active synthetic agonists, pralmorelin and macimorelin, been approved as diagnostic agents for GHD to date.…”

Section: Introductionmentioning

confidence: 99%

Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor

et al. 2021

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Ghrelin, also called “the hunger hormone”, is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward, cognition, learning and memory. One unique feature of ghrelin is its acylation, primarily with an octanoic acid, which is essential for its binding and activation of the ghrelin receptor, a G protein-coupled receptor. The multifaceted roles of ghrelin make ghrelin receptor a highly attractive drug target for growth retardation, obesity, and metabolic disorders. Here we present two cryo-electron microscopy structures of Gq-coupled ghrelin receptor bound to ghrelin and a synthetic agonist, GHRP-6. Analysis of these two structures reveals a unique binding pocket for the octanoyl group, which guides the correct positioning of the peptide to initiate the receptor activation. Together with mutational and functional data, our structures define the rules for recognition of the acylated peptide hormone and activation of ghrelin receptor, and provide structural templates to facilitate drug design targeting ghrelin receptor.

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“…Several human genetic studies identified rare mutations and single nucleotide polymorphisms (SNPs) in the gene encoding ghrelin receptor, which might be associated with human obesity and short stature [60]. Moreover, two SNPs in the receptor (Ala204Glu and Phe279Leu) have been associated with obesity and very short height [61].…”

Section: Ghrelinmentioning

confidence: 99%

Obesity–An Update on the Basic Pathophysiology and Review of Recent Therapeutic Advances

et al. 2021

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Obesity represents a major public health problem with a prevalence increasing at an alarming rate worldwide. Continuous intensive efforts to elucidate the complex pathophysiology and improve clinical management have led to a better understanding of biomolecules like gut hormones, antagonists of orexigenic signals, stimulants of fat utilization, and/or inhibitors of fat absorption. In this article, we will review the pathophysiology and pharmacotherapy of obesity including intersection points to the new generation of antidiabetic drugs. We provide insight into the effectiveness of currently approved anti-obesity drugs and other therapeutic avenues that can be explored.

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Ghrelin Receptor Mutations and Human Obesity

Cited by 19 publications

References 78 publications

Signaling pathways in obesity: mechanisms and therapeutic interventions

Signaling pathways in obesity: mechanisms and therapeutic interventions

Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor

Obesity–An Update on the Basic Pathophysiology and Review of Recent Therapeutic Advances

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