Department of Endocrinology, Hospital Ramón y Cajal, Ctra. de colmenar, Km 9,100, 28034 Madrid, Spain.
Eur J Endocrinol. 2012 Sep;167(3):301-9. doi: 10.1530/EJE-12-0357. Epub 2012 Jun 27.
Fibroblast growth factor 21 (FGF21), a 181 amino acid circulating protein, is a member of the FGF superfamily, with relevant metabolic actions. It acts through the interaction with specific FGF receptors and a cofactor called β-Klotho, whose expression is predominantly detected in metabolically active organs. FGF21 stimulates glucose uptake in adipocytes via the induction of glucose transporter-1. This action is additive and independent of insulin. β-Cell function and survival are preserved, and glucagon secretion is reduced by this protein, thus decreasing hepatic glucose production and improving insulin sensitivity. Lipid profile has been shown to be improved by FGF21 in several animal models. FGF21 increases energy expenditure in rodents and induces weight loss in diabetic nonhuman primates. It also exerts favorable effects on hepatic steatosis and reduces tissue lipid content in rodents. Adaptive metabolic responses to fasting, including stimulation of ketogenesis and fatty acid oxidation, seem to be partially mediated by FGF21. In humans, serum FGF21 concentrations have been found elevated in insulin-resistant states, such as impaired glucose tolerance and type 2 diabetes. FGF21 levels are correlated with hepatic insulin resistance index, fasting blood glucose, HbA1c, and blood glucose after an oral glucose tolerance test. A relationship between FGF21 levels and long-term diabetic complications, such as nephropathy and carotid atheromatosis, has been reported. FGF21 levels decreased in diabetic patients after starting therapy with insulin or oral agents. Increased FGF21 serum levels have also been found to be associated with obesity. In children, it is correlated with BMI and leptin levels, whereas in adults, FGF21 levels are mainly related to several components of the metabolic syndrome. Serum FGF21 levels have been found to be elevated in patients with ischemic heart disease. In patients with renal disease, FGF21 levels exhibited a progressive increase as renal function deteriorates. Circulating FGF21 levels seem to be related to insulin resistance and inflammation in dialysis patients. In summary, FGF21 is a recently identified hormone with antihyperglycemic, antihyperlipidemic, and thermogenic properties. Direct or indirect potentiation of its effects might be a potential therapeutic target in insulin-resistant states.
成纤维细胞生长因子 21（FGF21）是一种 181 个氨基酸的循环蛋白，属于成纤维细胞生长因子超家族，具有相关的代谢作用。它通过与特定的成纤维细胞生长因子受体和一种称为β-Klotho 的辅助因子相互作用发挥作用，β-Klotho 的表达主要在代谢活跃的器官中检测到。FGF21 通过诱导葡萄糖转运蛋白-1 刺激脂肪细胞摄取葡萄糖。这种作用是累加的，且不依赖于胰岛素。该蛋白可保护β细胞功能和存活，并减少胰高血糖素分泌，从而降低肝葡萄糖生成并改善胰岛素敏感性。在几种动物模型中已显示 FGF21 可改善血脂谱。FGF21 可增加啮齿动物的能量消耗并诱导非人类糖尿病灵长类动物减轻体重。它还可对肝脂肪变性产生有利影响并减少啮齿动物组织中的脂质含量。禁食引起的适应性代谢反应，包括酮体生成和脂肪酸氧化的刺激，似乎部分由 FGF21 介导。在人类中，已发现血清 FGF21 浓度在胰岛素抵抗状态下升高，如糖耐量受损和 2 型糖尿病。FGF21 水平与肝胰岛素抵抗指数、空腹血糖、HbA1c 和口服葡萄糖耐量试验后的血糖相关。已经报道了 FGF21 水平与长期糖尿病并发症（如肾病和颈动脉粥样硬化）之间的关系。开始胰岛素或口服药物治疗后，糖尿病患者的 FGF21 水平下降。还发现血清 FGF21 水平升高与肥胖有关。在儿童中，它与 BMI 和瘦素水平相关，而在成人中，FGF21 水平主要与代谢综合征的几个成分相关。在缺血性心脏病患者中发现血清 FGF21 水平升高。在肾功能恶化的肾病患者中，FGF21 水平呈进行性升高。在透析患者中，循环 FGF21 水平似乎与胰岛素抵抗和炎症有关。总之，FGF21 是一种新发现的具有降血糖、降血脂和产热特性的激素。直接或间接增强其作用可能是胰岛素抵抗状态的潜在治疗靶点。
