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FGF19 在代谢调节中的作用:从临床前模型到临床试验的见解。

The role of FGF19 in metabolic regulation: insights from preclinical models to clinical trials.

机构信息

Faculdade Israelita de Ciências da Saúde Albert Einstein, Hospital Israelita Albert Einstein, São Paulo, Brazil.

Hospital Israelita Albert Einstein, São Paulo, Brazil.

出版信息

Am J Physiol Endocrinol Metab. 2024 Sep 1;327(3):E279-E289. doi: 10.1152/ajpendo.00156.2024. Epub 2024 Jul 17.

DOI:10.1152/ajpendo.00156.2024
PMID:39017679
Abstract

Fibroblast growth factor 19 (FGF19) is a hormone synthesized in enterocytes in response to bile acids. This review explores the pivotal role of FGF19 in metabolism, addressing the urgent global health concern of obesity and its associated pathologies, notably type 2 diabetes. The intriguing inverse correlation between FGF19 and body mass or visceral adiposity, as well as its rapid increase following bariatric surgery, emphasizes its potential as a therapeutic target. This article meticulously examines the impact of FGF19 on metabolism by gathering evidence primarily derived from studies conducted in animal models or cell lines, using both FGF19 treatment and genetic modifications. Overall, these studies demonstrate that FGF19 has antidiabetic and antiobesogenic effects. A thorough examination across metabolic tissues, including the liver, adipose tissue, skeletal muscle, and the central nervous system, is conducted, unraveling the intricate interplay of FGF19 across diverse organs. Moreover, we provide a comprehensive overview of clinical trials involving an FGF19 analog called aldafermin, emphasizing promising results in diseases such as nonalcoholic steatohepatitis and diabetes. Therefore, we aim to foster a deeper understanding of FGF19 role and encourage further exploration of its clinical applications, thereby advancing the field and offering innovative approaches to address the escalating global health challenge of obesity and related metabolic conditions.

摘要

成纤维细胞生长因子 19(FGF19)是一种在肠细胞中响应胆汁酸合成的激素。本综述探讨了 FGF19 在代谢中的关键作用,解决了肥胖及其相关病理的紧迫全球健康问题,特别是 2 型糖尿病。FGF19 与体重或内脏脂肪呈负相关,以及在减肥手术后迅速增加,这强调了它作为治疗靶点的潜力。本文通过汇集主要来自动物模型或细胞系的研究中获得的证据,仔细研究了 FGF19 对代谢的影响,使用了 FGF19 治疗和遗传修饰。总的来说,这些研究表明 FGF19 具有抗糖尿病和抗肥胖作用。对包括肝脏、脂肪组织、骨骼肌和中枢神经系统在内的代谢组织进行了全面检查,揭示了 FGF19 在不同器官中的复杂相互作用。此外,我们还对涉及 FGF19 类似物aldafermin 的临床试验进行了全面概述,强调了其在非酒精性脂肪性肝炎和糖尿病等疾病中的有希望的结果。因此,我们旨在深入了解 FGF19 的作用,并鼓励进一步探索其临床应用,从而推进该领域的发展,并提供创新的方法来应对肥胖和相关代谢状况这一日益严重的全球健康挑战。

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