Background: Ghrelin, a unique 28 amino acid peptide hormone secreted by the gastric X/A like cells, is an endogenous ligand of the growth hormone secretagogue receptor (GHSR). Ghrelin-GHSR signaling has been found to exert various physiological functions, including stimulation of appetite, regulation of body weight, lipid and glucose metabolism, and increase of gut motility and secretion. This system is thus critical for energy homeostasis.

Objective: The objective of this review is to highlight the strategies of ghrelin-GHSR based intervention for therapy of obesity and its related metabolic diseases.

Results: Therapeutic strategies of metabolic disorders targeting the ghrelin-GHSR pathway involve neutralization of circulating ghrelin by antibodies and RNA spiegelmers, antagonism of ghrelin receptor by its antagonists and inverse agonists, inhibition of ghrelin O-acyltransferase (GOAT), as well as potential pharmacological approach to decrease ghrelin synthesis and secretion.

Conclusion: Various compounds targeting the ghrelin-GHSR system have shown promising efficacy for the intervention of obesity and relevant metabolic disorders in animals and in vitro. Further clinical trials to validate their efficacy in human beings are urgently needed.

背景：Ghrelin 是一种由胃 X/A 样细胞分泌的独特的 28 个氨基酸肽激素，是生长激素促分泌素受体 (GHSR) 的内源性配体。已发现 Ghrelin-GHSR 信号传导发挥多种生理功能，包括刺激食欲、调节体重、脂质和葡萄糖代谢，以及增加肠道运动和分泌。因此，该系统对于能量稳态至关重要。

目的：本综述的目的是强调基于 ghrelin-GHSR 的肥胖及其相关代谢疾病治疗的干预策略。

结果：针对 ghrelin-GHSR 途径的代谢疾病的治疗策略包括通过抗体和 RNA spiegelmers 中和循环 ghrelin、通过其拮抗剂和反向激动剂拮抗 ghrelin 受体、抑制 ghrelin O-酰基转移酶 (GOAT) 以及潜在的药理作用。减少生长素释放肽合成和分泌的方法。

结论：多种靶向 ghrelin-GHSR 系统的化合物在动物和体外干预肥胖和相关代谢紊乱方面显示出良好的疗效。迫切需要进一步的临床试验来验证它们在人类中的功效。