The unexpected role of GIP in transforming obesity treatment.

IF 11.4 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Trends in Endocrinology and Metabolism Pub Date : 2024-08-27 DOI:10.1016/j.tem.2024.07.022
Inuk Zandvakili, Diego Perez-Tilve
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Abstract

Despite sharing incretin activity with glucagon-like peptide 1 (GLP-1), the development of gastric inhibitory polypeptide (GIP)-based drugs has been hindered by the minor effects of native GIP on appetite and body weight and genetic studies associating loss-of-function with reduced obesity. Yet, pharmacologically optimized GIP-based molecules have demonstrated profound weight lowering benefits of GIPR agonism when combined with GLP-1-based therapies, which has re-energized deeper exploration of the molecular mechanisms and downstream signaling of GIPR. Interestingly, both GIPR agonism and antagonism offer metabolic benefits, leading to differing viewpoints on how to target GIPR therapeutically. Here we summarize the emerging evidence about the tissue-specific mechanisms that positions GIP-based therapies as important targets for the next generation of anti-obesity and metabolic therapies.

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GIP 在改变肥胖症治疗方面发挥了意想不到的作用。
尽管胃抑制多肽(GIP)与胰高血糖素样肽 1(GLP-1)具有相同的增量素活性,但由于原生 GIP 对食欲和体重的影响较小,而且基因研究表明功能缺失会导致肥胖症减轻,因此阻碍了基于 GIP 的药物的开发。然而,经过药理优化的 GIP 分子与基于 GLP-1 的疗法相结合后,GIPR 激动剂具有显著的降低体重的功效,这重新激发了对 GIPR 分子机制和下游信号传导的深入探索。有趣的是,GIPR 的激动和拮抗作用都能带来新陈代谢方面的益处,这导致人们对如何针对 GIPR 进行治疗产生了不同的观点。在此,我们总结了有关组织特异性机制的新证据,这些证据将基于 GIP 的疗法定位为下一代抗肥胖和代谢疗法的重要靶点。
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来源期刊
Trends in Endocrinology and Metabolism
Trends in Endocrinology and Metabolism 医学-内分泌学与代谢
CiteScore
20.10
自引率
0.00%
发文量
98
审稿时长
82 days
期刊介绍: Trends in Endocrinology and Metabolism (TEM) stands as a premier Reviews journal in the realms of metabolism and endocrinology. Our commitment is reflected in the publication of refined, concise, and highly impactful articles that delve into cutting-edge topics, encompassing basic, translational, and clinical aspects. From state-of-the-art treatments for endocrine diseases to groundbreaking developments in molecular biology, TEM provides comprehensive coverage. Explore recent advancements in diabetes, endocrine diseases, obesity, neuroendocrinology, immunometabolism, molecular and cellular biology, and a myriad of other areas through our journal. TEM serves as an invaluable resource for researchers, clinicians, lecturers, teachers, and students. Each monthly issue is anchored by Reviews and Opinion articles, with Reviews meticulously chronicling recent and significant developments, often contributed by leading researchers in specific fields. Opinion articles foster debate and hypotheses. Our shorter pieces include Science & Society, shedding light on issues at the intersection of science, society, and policy; Spotlights, which focus on exciting recent developments in the literature, and single-point hypotheses as Forum articles. We wholeheartedly welcome and encourage responses to previously published TEM content in the form of Letters.
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