{"title":"The unexpected role of GIP in transforming obesity treatment.","authors":"Inuk Zandvakili, Diego Perez-Tilve","doi":"10.1016/j.tem.2024.07.022","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54415,"journal":{"name":"Trends in Endocrinology and Metabolism","volume":" ","pages":""},"PeriodicalIF":11.4000,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in Endocrinology and Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.tem.2024.07.022","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
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.
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.
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