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Fibroblast Growth Factor Signaling in Metabolic Regulation

机译:代谢调控中的成纤维细胞生长因子信号

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The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance, and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed. In this review, we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also, the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease and to provide starting points for the development of FGF-based therapies against metabolic conditions.
机译:肥胖的流行是日益严重的健康问题。肥胖与多种合并症密切相关,例如非酒精性脂肪性肝病,某些癌症,胰岛素抵抗和2型糖尿病,这些都会降低预期寿命和生活质量。已经提出了几种药物来治疗这些疾病,但是许多药物具有有害的副作用。成纤维细胞生长因子家族在能量代谢调节中的出乎意料的作用为治疗代谢性疾病提供了新方法,并提供了有价值的工具来深入了解代谢调节。 FGF19和FGF21对代谢的已知有益作用以及最近发现的FGF1类似作用表明,FGF及其衍生物具有巨大的潜力,可作为治疗代谢疾病的新疗法。为了促进具有改善的靶向性和最小的副作用的新疗法的发展,需要对FGF作用的分子机制有更好的了解。在这篇综述中,我们将讨论关于FGF信号转导在对体内代谢稳态很重要的组织中的生理作用的当前已知信息。此外,在代谢性疾病的背景下,我们将讨论有关其药理特性和效应器组织的最新概念。同样,将综述FGF变体开发中的最新进展。我们的目标是全面概述有关代谢健康和疾病中FGF信号传导的当前概念和共识,并为开发针对代谢状况的FGF疗法提供起点。

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