Center for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA; Division of Endocrinology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA; Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, USA.
Center for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA; Division of Endocrinology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA; Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, USA.
Mol Metab. 2021 Apr;46:101128. doi: 10.1016/j.molmet.2020.101128. Epub 2020 Nov 25.
The hormone ghrelin stimulates food intake, promotes adiposity, increases body weight, and elevates blood glucose. Consequently, 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.
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.
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.
激素 ghrelin 可刺激食欲、促进肥胖、增加体重并提高血糖。因此，血浆 ghrelin 水平的改变和更广泛的 ghrelin 系统的其他组成部分的功能被认为是肥胖和糖尿病的潜在诱因。此外，靶向 ghrelin 系统已被提议作为肥胖和糖尿病的一种新的治疗策略。
本综述重点关注将 ghrelin 及其作为肥胖和糖尿病治疗的 ghrelin 系统的其他蛋白质作为治疗靶点的潜力。介绍了 ghrelin 系统的主要组成部分。概述了支持内源性 ghrelin 系统在肥胖和糖尿病发展中起作用的数据，以及似乎否定这种作用的数据。阐述了进一步研究 ghrelin 系统靶向治疗剂开发的理由。还提供了基于证据的关于可能影响这类治疗剂疗效的潜在因素和情况的讨论。
可以合理地认为，靶向 ghrelin 系统的药物，包括降低酰基 ghrelin 水平、提高 LEAP2 水平、阻断 GHSR 活性和/或提高去酰基 ghrelin 信号的药物，可能成为肥胖和糖尿病的有效新型治疗方法。
