Cuevas-Ramos Daniel, Aguilar-Salinas Carlos A
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Horm Mol Biol Clin Investig. 2016 Jun 20;30(1):/j/hmbci.2017.30.issue-1/hmbci-2016-0023/hmbci-2016-0023.xml. doi: 10.1515/hmbci-2016-0023.
Fibroblast growth factors (FGFs) are a superfamily of 22 proteins related to cell proliferation and tissue repair after injury. A subgroup of three proteins, FGF19, FGF21, and FGF23, are major endocrine mediators. These three FGFs have low affinity to heparin sulfate during receptor binding; in contrast they have a strong interaction with the cofactor Klotho/β-Klotho. FGF21 has received particular attention because of its key role in carbohydrate, lipids, and energy balance regulation. FGF21 improves glucose and lipids metabolism as well as increasing energy expenditure in animal models and humans. Conditions that induce human physical stress such as exercise, lactation, obesity, insulin resistance, and type 2 diabetes influence FGF21 circulating levels. FGF21 also has an anti-oxidant function in human metabolic diseases which contribute to understanding the FGF21 compensatory increment in obesity, the metabolic syndrome, and type 2 diabetes. Interestingly, energy expenditure and weight loss is induced by FGF21. The mechanism involved is through "browning" of white adipose tissue, increasing brown adipose tissue activity and heat production. Therefore, clinical evaluation of therapeutic action of exogenous FGF21 administration is warranted, particularly to treat diabetes and obesity.
成纤维细胞生长因子（FGFs）是一个由22种蛋白质组成的超家族，与损伤后的细胞增殖和组织修复有关。FGF19、FGF21和FGF23这三种蛋白质组成的亚群是主要的内分泌介质。这三种FGF在受体结合过程中对硫酸乙酰肝素的亲和力较低；相反，它们与辅因子α-klotho/β-klotho有很强的相互作用。FGF21因其在碳水化合物、脂质和能量平衡调节中的关键作用而受到特别关注。在动物模型和人类中，FGF21可改善葡萄糖和脂质代谢，并增加能量消耗。运动、哺乳、肥胖、胰岛素抵抗和2型糖尿病等诱发人类身体应激的情况会影响FGF21的循环水平。FGF21在人类代谢疾病中还具有抗氧化功能，这有助于理解肥胖、代谢综合征和2型糖尿病中FGF21的代偿性增加。有趣的是，FGF21可诱导能量消耗和体重减轻。其涉及的机制是通过白色脂肪组织的“褐变”，增加棕色脂肪组织的活性和产热。因此，有必要对外源性FGF21给药的治疗作用进行临床评估，特别是用于治疗糖尿病和肥胖症。
