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肥胖的分子机制及其在当前和未来治疗中的潜在应用。

Molecular Mechanisms behind Obesity and Their Potential Exploitation in Current and Future Therapy.

机构信息

Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Medyków 18, 40-752 Katowice, Poland.

出版信息

Int J Mol Sci. 2024 Jul 27;25(15):8202. doi: 10.3390/ijms25158202.

Abstract

Obesity is a chronic disease caused primarily by the imbalance between the amount of calories supplied to the body and energy expenditure. Not only does it deteriorate the quality of life, but most importantly it increases the risk of cardiovascular diseases and the development of type 2 diabetes mellitus, leading to reduced life expectancy. In this review, we would like to present the molecular pathomechanisms underlying obesity, which constitute the target points for the action of anti-obesity medications. These include the central nervous system, brain-gut-microbiome axis, gastrointestinal motility, and energy expenditure. A significant part of this article is dedicated to incretin-based drugs such as GLP-1 receptor agonists (e.g., liraglutide and semaglutide), as well as the brand new dual GLP-1 and GIP receptor agonist tirzepatide, all of which have become "block-buster" drugs due to their effectiveness in reducing body weight and beneficial effects on the patient's metabolic profile. Finally, this review article highlights newly designed molecules with the potential for future obesity management that are the subject of ongoing clinical trials.

摘要

肥胖是一种由摄入体内的卡路里量与能量消耗之间的不平衡引起的慢性疾病。它不仅降低了生活质量,而且最重要的是增加了心血管疾病和 2 型糖尿病的风险,导致预期寿命缩短。在这篇综述中,我们希望介绍肥胖症的分子病理机制,这些机制是抗肥胖药物作用的靶点。这些靶点包括中枢神经系统、脑-肠-微生物群轴、胃肠道动力和能量消耗。本文的重要部分专门介绍了基于肠促胰岛素的药物,如 GLP-1 受体激动剂(如利拉鲁肽和司美格鲁肽),以及全新的双重 GLP-1 和 GIP 受体激动剂替西帕肽,它们都因在减轻体重和改善患者代谢特征方面的有效性而成为“重磅炸弹”药物。最后,这篇综述文章强调了具有未来肥胖症管理潜力的新设计分子,这些分子是正在进行的临床试验的主题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9d/11311839/9d58e70f874d/ijms-25-08202-g001.jpg

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