Metabolic Research Laboratory, Clínica Universidad de Navarra, Avda. Pío XII, 36, 31008, Pamplona, Spain.
CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.
Curr Diab Rep. 2017 Jun;17(6):43. doi: 10.1007/s11892-017-0866-3.
Obesity and its associated metabolic diseases have reached epidemic proportions worldwide, reducing life expectancy and quality of life. Several drugs have been tested to treat these diseases but many of them have damaging side effects. Consequently, there is an urgent need to develop more effective therapies. Recently, endocrine fibroblast growth factors (FGFs) have become attractive targets in the treatment of metabolic diseases. This review summarizes their most important functions as well as FGF-based therapies for the treatment of obesity and type 2 diabetes (T2D).
Recent studies demonstrate that circulating levels of FGF19 are reduced in obesity. In fact, exogenous FGF19 administration is associated with a reduction in food intake as well as with improvements in glycaemia. In contrast, FGF21 levels are elevated in subjects with abdominal obesity, insulin resistance and T2D, probably representing a compensatory response. Additionally, elevated levels of circulating FGF23 in individuals with obesity and T2D are reported in most clinical studies. Finally, increased FGF1 levels in obese patients associated with adipogenesis have been described. FGFs constitute important molecules in the treatment of metabolic diseases due to their beneficial effects on glucose and lipid metabolism. Among all members, FGF19 and FGF21 have demonstrated the ability to improve glucose, lipid and energy homeostasis, along with FGF1, which was recently discovered to have beneficial effects on metabolic homeostasis. Additionally, FGF23 may also play a role in insulin resistance or energy homeostasis beyond mineral metabolism control. These results highlight the relevant use of FGFs as potential biomarkers for the early diagnosis of metabolic diseases. In this regard, notable progress has been made in the development of FGF-based therapies and different approaches are being tested in different clinical trials. However, further studies are needed to determine their potential therapeutic use in the treatment of obesity and obesity-related comorbidities.
综述目的：肥胖及其相关代谢性疾病在全球范围内已达到流行程度，降低了预期寿命和生活质量。已经测试了几种药物来治疗这些疾病，但其中许多药物都有不良的副作用。因此，迫切需要开发更有效的治疗方法。最近，内分泌成纤维细胞生长因子（FGFs）已成为治疗代谢性疾病的有吸引力的靶点。本综述总结了它们最重要的功能以及基于 FGF 的治疗肥胖和 2 型糖尿病（T2D）的方法。
最新发现：最近的研究表明，肥胖症患者的循环 FGF19 水平降低。事实上，外源性 FGF19 给药与食物摄入减少以及血糖改善有关。相比之下，腹部肥胖、胰岛素抵抗和 T2D 患者的 FGF21 水平升高，可能代表一种代偿反应。此外，大多数临床研究报告肥胖和 T2D 个体的循环 FGF23 水平升高。最后，在肥胖患者中与脂肪生成相关的 FGF1 水平增加已被描述。由于对葡萄糖和脂质代谢的有益作用，FGFs 成为治疗代谢性疾病的重要分子。在所有成员中，FGF19 和 FGF21 已被证明具有改善葡萄糖、脂质和能量稳态的能力，而最近发现 FGF1 对代谢稳态具有有益作用。此外，FGF23 可能在胰岛素抵抗或能量稳态方面发挥作用，而不仅仅是在矿物质代谢控制方面。这些结果强调了 FGFs 作为代谢性疾病早期诊断的潜在生物标志物的重要作用。在这方面，基于 FGF 的治疗方法的开发取得了显著进展，并且正在不同的临床试验中测试不同的方法。然而，还需要进一步的研究来确定它们在治疗肥胖和肥胖相关合并症方面的潜在治疗用途。
