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

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM American journal of physiology. Endocrinology and metabolism Pub Date : 2024-09-01 Epub Date: 2024-07-17 DOI:10.1152/ajpendo.00156.2024
Marcela Botelho de Carvalho, Gabriel Machado Chavez Passos Jorge, Luiza Wolf Zanardo, Leticia Miho Hamada, Larissa Dos Santos Izabel, Sergio Santoro, Juliana Magdalon
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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.

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FGF19在新陈代谢调节中的作用:从临床前模型到临床试验的启示。
成纤维细胞生长因子 19 (FGF19) 是一种在肠细胞中合成的激素,对胆汁酸做出反应。本综述探讨了 FGF19 在新陈代谢中的关键作用,探讨了肥胖及其相关病症(尤其是 2 型糖尿病)这一紧迫的全球健康问题。FGF19与体重或内脏脂肪率之间存在着令人感兴趣的反相关关系,而且在减肥手术后FGF19会迅速增加,这都强调了FGF19作为治疗靶点的潜力。本文通过收集主要来自动物模型或细胞系研究的证据,采用 FGF19 治疗和基因修饰方法,细致研究了 FGF19 对新陈代谢的影响。总体而言,这些研究表明 FGF19 具有抗糖尿病和抗肥胖的作用。我们对肝脏、脂肪组织、骨骼肌和中枢神经系统等新陈代谢组织进行了深入研究,揭示了 FGF19 在不同器官中错综复杂的相互作用。此外,我们还全面综述了一种名为 aldafermin 的 FGF19 类似物的临床试验,强调了其在非酒精性脂肪性肝炎和糖尿病等疾病中的良好效果。因此,我们旨在加深对 FGF19 作用的理解,并鼓励进一步探索其临床应用,从而推动该领域的发展,并提供创新方法来应对肥胖和相关代谢疾病这一不断升级的全球健康挑战。
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来源期刊
CiteScore
9.80
自引率
0.00%
发文量
98
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Endocrinology and Metabolism publishes original, mechanistic studies on the physiology of endocrine and metabolic systems. Physiological, cellular, and molecular studies in whole animals or humans will be considered. Specific themes include, but are not limited to, mechanisms of hormone and growth factor action; hormonal and nutritional regulation of metabolism, inflammation, microbiome and energy balance; integrative organ cross talk; paracrine and autocrine control of endocrine cells; function and activation of hormone receptors; endocrine or metabolic control of channels, transporters, and membrane function; temporal analysis of hormone secretion and metabolism; and mathematical/kinetic modeling of metabolism. Novel molecular, immunological, or biophysical studies of hormone action are also welcome.
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