Li Min, Chen Ying, Jiang Jingjing, Lu Yan, Song Zhiyi, Zhang Shengjie, Sun Chao, Ying Hao, Fan Xiaofang, Song Yuping, Yang Jialin, Zhao Lin
Department of Endocrinology and Metabolism, Fudan Institute of Metabolic Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Endocr Connect. 2019 Jun 1;8(6):728-735. doi: 10.1530/EC-19-0175.
Recent studies have shown that neuregulin 4 (Nrg4), a member of the epidermal growth factor (EGF) family of extracellular ligands, plays an important role in the prevention of obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD). Considering that thyroid hormone (TH) has profound effects on whole-body energy metabolism, we speculate that circulating Nrg4 levels might be altered in patients with hyperthyroidism.
A total of 129 hyperthyroid patients and 100 healthy subjects were recruited. Of them, 39 hyperthyroid patients received thionamide treatment for 3 months until euthyroidism. Serum Nrg4 levels were determined using the ELISA method. To further confirm the relationship between TH and Nrg4, C57BL/6 mice were treated with T3 and quantitative real-time PCR was performed to detect Nrg4 gene expression.
Serum Nrg4 levels were significantly elevated in hyperthyroid patients as compared with normal controls (3.84 ± 1.63 vs 2.21 ± 1.04 ng/mL, P < 0.001). After achieving euthyroidism by thionamide treatment, serum Nrg4 levels dropped markedly from 3.57 ± 1.26 to 1.94 ± 0.72 ng/ml (P < 0.001). After adjustment for potential confounders, serum Nrg4 levels were independently associated with hyperthyroidism. The upregulation of Nrg4 expression in the livers and white adipose tissues by T3 was further confirmed by animal and cell culture experiments.
Serum Nrg4 levels were increased in patients with hyperthyroidism. The liver and white adipose tissue might be primary sources contributing to elevated serum Nrg4 concentrations.
近期研究表明，神经调节蛋白4（Nrg4）作为细胞外配体的表皮生长因子（EGF）家族成员，在预防肥胖、胰岛素抵抗和非酒精性脂肪性肝病（NAFLD）中发挥重要作用。鉴于甲状腺激素（TH）对全身能量代谢有深远影响，我们推测甲状腺功能亢进患者的循环Nrg4水平可能会发生改变。
共招募了129例甲状腺功能亢进患者和100名健康受试者。其中，39例甲状腺功能亢进患者接受硫代酰胺治疗3个月直至甲状腺功能正常。采用酶联免疫吸附测定（ELISA）法测定血清Nrg4水平。为进一步证实TH与Nrg4之间的关系，对C57BL/6小鼠进行T3处理，并进行定量实时聚合酶链反应（PCR）以检测Nrg4基因表达。
与正常对照组相比，甲状腺功能亢进患者的血清Nrg4水平显著升高（3.84±1.63对2.21±1.04 ng/mL，P<0.001）。通过硫代酰胺治疗实现甲状腺功能正常后，血清Nrg4水平从3.57±1.26显著降至1.94±0.72 ng/ml（P<0.001）。在调整潜在混杂因素后，血清Nrg4水平与甲状腺功能亢进独立相关。动物和细胞培养实验进一步证实了T3对肝脏和白色脂肪组织中Nrg4表达的上调作用。
甲状腺功能亢进患者的血清Nrg4水平升高。肝脏和白色脂肪组织可能是导致血清Nrg4浓度升高的主要来源。
