Half a decade ago, transmembrane protein fibronectin type III domain-containing protein 5 (FNDC5) was found to be cleaved as a novel myokine irisin, which burst into prominence for browning of white adipose tissue during exercise. However, FNDC5, the precursor of irisin, has been paid relatively little attention compared with irisin despite evidence that FNDC5 is associated with the metabolic syndrome, which accounts for one-fourth of the world's adult population and contributes to diabetes, cardiovascular disease and all-cause mortality. Besides N-terminal and C-terminal sequences, the FNDC5 protein contains an irisin domain and a short transmembrane region. FNDC5 has shown to be widely distribute in different tissues and is highly expressed in heart, brain, liver, and skeletal muscle. Clinical studies have demonstrated that FNDC5 is essential for maintaining metabolic homeostasis and dysregulation of FNDC5 will lead to systemic metabolism imbalance and the onset of metabolic disorders. Growing evidence has suggested that FNDC5 gene polymorphisms are related to health and disease in different human populations. Additionally, FNDC5 has been found relevant to the regulation of metabolism and metabolic syndrome through diverse upstream and downstream signaling pathways in experimental studies. The present review summarizes the characteristics, clinical significance, and molecular mechanisms of FNDC5 in metabolic syndrome and proposes a novel concept that FNDC5 is activated by forming a putative ligand-receptor complex. Knowledge about the role of FNDC5 may be translated into drug development and clinical applications for the treatment of metabolic disorders.

半个十年前，发现跨膜蛋白纤连蛋白III型结构域蛋白5（FNDC5）被裂解为一种新型的肌动蛋白鸢尾素，在运动过程中突显出白色脂肪组织的褐变。然而，尽管有证据表明FNDC5与代谢综合征有关，而FNDC5是鸢尾素的前体，而FNDC5与代谢综合征有关，代谢综合征占世界成年人口的四分之一，并导致糖尿病，心血管疾病和所有疾病。导致死亡。除了N端和C端序列外，FNDC5蛋白还包含一个虹膜素结构域和一个短跨膜区。FNDC5已显示广泛分布在不同的组织中，并在心脏，大脑，肝脏和骨骼肌中高度表达。临床研究表明，FNDC5对于维持代谢稳态是必不可少的，而FNDC5的失调将导致系统性代谢失衡和新陈代谢紊乱的发作。越来越多的证据表明，FNDC5基因多态性与不同人群的健康和疾病有关。此外，在实验研究中，已发现FNDC5与代谢和代谢综合症的调节有关，通过多种上游和下游信号传导途径。本综述概述了代谢综合征中FNDC5的特征，临床意义和分子机制，并提出了一个新的概念，即FNDC5通过形成推定的配体-受体复合物而被激活。