Background

The hormone ghrelin stimulates food intake, promotes adiposity, increases body weight, and elevates blood glucose. Consquently, alterations in plasma ghrelin levels and the functioning of other components of the broader ghrelin system have been proposed as potential contributors to obesity and diabetes. Furthermore, targeting the ghrelin system has been proposed as a novel therapeutic strategy for obesity and diabetes.

Scope of Review

The current review focuses on the potential for targeting ghrelin and other proteins comprising the ghrelin system as a treatment for obesity and diabetes. The main components of the ghrelin system are introduced. Data supporting a role for the endogenous ghrelin system in the development of obesity and diabetes along with data that seemingly refute such a role are outlined. An argument for further research into the development of ghrelin system-targeted therapeutic agents is delineated. Also, an evidence-based discussion of potential factors and contexts that might influence the efficacy of this class of therapeutics is provided.

Major Conclusions

It would not be a “leap to” conclusions to suggest that agents which target the ghrelin system – including those that lower acyl-ghrelin levels, raise LEAP2 levels, block GHSR activity, and/or raise desacyl-ghrelin signaling – could represent efficacious novel treatments for obesity and diabetes.

中文翻译：

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“A LEAP 2 结论？：针对 Ghrelin 系统治疗肥胖和糖尿病”

背景

激素ghrelin刺激食物摄入，促进肥胖，增加体重，并升高血糖。因此，血浆 ghrelin 水平的改变和更广泛的 ghrelin 系统其他成分的功能被认为是肥胖和糖尿病的潜在因素。此外，针对 ghrelin 系统已被提议作为肥胖和糖尿病的新治疗策略。

审查范围

当前的审查重点关注靶向生长素释放肽和其他包含生长素释放肽系统的蛋白质作为治疗肥胖症和糖尿病的潜力。介绍了ghrelin系统的主要组成部分。概述了支持内源性生长素释放肽系统在肥胖和糖尿病发展中的作用的数据以及似乎反驳这种作用的数据。描述了进一步研究开发生长素释放肽系统靶向治疗剂的论点。此外，还提供了对可能影响此类疗法疗效的潜在因素和背景的循证讨论。

主要结论

建议针对 ghrelin 系统的药剂——包括那些降低酰基 - ghrelin 水平、提高 LEAP2 水平、阻断 GHSR 活性和/或提高去酰基 - ghrelin 信号传导的试剂 - 可以代表有效的小说，这并不是一个“飞跃”的结论肥胖症和糖尿病的治疗方法。