Abstract：
UNASSIGNED: One billion people live with obesity. The most promising medications for its treatment are incretin-based therapies, based on enteroendocrine peptides released in response to oral nutrients, specifically glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The mechanisms by which GLP-1 receptor agonism cause weight reduction are becoming increasingly understood. However, the mechanisms by which GIP receptor-modulating medications cause weight loss remain to be clarified.
UNASSIGNED: This review describes GLP-1 and GIP physiology and explores the conflicting data regarding GIP and weight management. It details examples of how to reconcile the contradictory findings that both GIP receptor agonism and antagonism cause weight reduction. Specifically, it discusses the concept of \'biased agonism\' wherein exogenous peptides cause different post-receptor signaling patterns than native ligands. It discusses how GIP effects in adipose tissue and the central nervous system may cause weight reduction. It describes GIP receptor-modulating compounds and their most current trials regarding weight reduction.
UNASSIGNED: Effects of GIP receptor-modulating compounds on different tissues have implications for both weight reduction and other cardiometabolic diseases. Further study is needed to understand the implications of GIP agonism on not just weight reduction, but also cardiovascular disease, liver disease, bone health and fat storage.
UNASSIGNED: This review describes GLP-1 and GIP physiology and explores the conflicting data regarding GIP and weight management. It details examples of how to reconcile the contradictory findings that both GIP receptor agonism and antagonism cause weight reduction. Specifically, it discusses the concept of \'biased agonism\' wherein exogenous peptides cause different post-receptor signaling patterns than native ligands. It discusses how GIP effects in adipose tissue and the central nervous system may cause weight reduction. It describes GIP receptor-modulating compounds and their most current trials regarding weight reduction.
UNASSIGNED: Effects of GIP receptor-modulating compounds on different tissues have implications for both weight reduction and other cardiometabolic diseases. Further study is needed to understand the implications of GIP agonism on not just weight reduction, but also cardiovascular disease, liver disease, bone health and fat storage.
摘要：
■10亿人患有肥胖症。最有前途的治疗药物是基于肠促胰岛素的治疗，基于响应口服营养素而释放的肠内分泌肽，特别是胰高血糖素样肽-1（GLP-1）和葡萄糖依赖性促胰岛素分泌肽（GIP）。GLP-1受体激动导致体重减轻的机制正变得越来越清楚。然而,GIP受体调节药物导致体重减轻的机制仍有待阐明.
■这篇综述描述了GLP-1和GIP生理学，并探讨了关于GIP和体重管理的相互矛盾的数据。它详细说明了如何调和GIP受体激动和拮抗作用导致体重减轻的矛盾发现的例子。具体来说,它讨论了“偏向激动”的概念，其中外源肽引起与天然配体不同的受体后信号模式。它讨论了脂肪组织和中枢神经系统中的GIP效应如何导致体重减轻。它描述了GIP受体调节化合物及其关于减肥的最新试验。
■GIP受体调节化合物对不同组织的作用对减轻体重和其他心脏代谢疾病都有影响。需要进一步的研究来了解GIP激动不仅对减肥的影响，还有心血管疾病，肝病,骨骼健康和脂肪储存。
■这篇综述描述了GLP-1和GIP生理学，并探讨了关于GIP和体重管理的相互矛盾的数据。它详细说明了如何调和GIP受体激动和拮抗作用导致体重减轻的矛盾发现的例子。具体来说,它讨论了“偏向激动”的概念，其中外源肽引起与天然配体不同的受体后信号模式。它讨论了脂肪组织和中枢神经系统中的GIP效应如何导致体重减轻。它描述了GIP受体调节化合物及其关于减肥的最新试验。
■GIP受体调节化合物对不同组织的作用对减轻体重和其他心脏代谢疾病都有影响。需要进一步的研究来了解GIP激动不仅对减肥的影响，还有心血管疾病，肝病,骨骼健康和脂肪储存。
