Elevated serum neuregulin 4 levels in patients with hyperthyroidism
ENDOCRINE CONNECTIONS
Authors: Li, Min; Chen, Ying; Jiang, Jingjing; Lu, Yan; Song, Zhiyi; Zhang, Shengjie; Sun, Chao; Ying, Hao; Fan, Xiaofang; Song, Yuping; Yang, Jialin; Zhao, Lin
Abstract
Objective: 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. Design and methods: 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 T-3 and quantitative real-time PCR was performed to detect Nrg4 gene expression. Results: 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 T-3 was further confirmed by animal and cell culture experiments. Conclusions: 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.
Differences in Neuregulin 4 Expression in Children: Effects of Fat Depots and Obese Status
ENDOCRINE RESEARCH
Authors: Wang, Ran; Zhou, Wei; Zhu, Xiaolei; Zhou, Nan; Yang, Fan; Sun, Bin; Li, Xiaonan
Abstract
Purpose To observe the expression of Nrg4, uncoupling protein-1 (UCP1), tumor necrosis factor alpha (TNF alpha), CD31, VE-cadherin/CDH5 and vascular endothelial growth factor A (VEGF-A) mRNA in abdominal subcutaneous (SC), omental (OM) adipose tissue in children with relation to anthropometric parameters. Further to verify the effect of inflammatory mediators on Nrg4 and UCP1 mRNA expression in adipocytes. Methods Paired SC and OM adipose tissues were obtained from 58 children. In vitro, the adipocytes isolated from primary inguinal adipose tissue of mice were treated with TNF alpha (50 ng/ml) for 12-48 h. mRNA levels of Nrg4, UCP1 and TNF alpha were determined by real-time PCR. Results Nrg4, UCP1, VEGF-A and CDH5 mRNA levels in SC were significantly higher than those in OM adipose tissue and the mRNA level of TNF alpha showed the opposite result. Moreover, Nrg4 and UCP1 mRNA in SC were significantly lower in overweight children compared to normal weight children. Nrg4 in SC and OM was negatively associated with BMISDS, WHtR. CDH55 mRNA in OM was negatively associated with WHR. VEGF-A was positively correlated with Nrg4 in SC. In vitro, Nrg4 and UCP1 mRNA levels in adipocytes were dose- and time-dependently decreased under TNF alpha treatment. Conclusions Nrg4, UCP1, VEGF-A and CDH5 mRNA expression in adipose tissues display a depot-specific pattern. Nrg4 mRNA levels in adipose tissue are decreased with obesity and associated with WAT browning and angiogenesis. TNF alpha may be involved in the regulation of Nrg4 level in adipose tissue, which may be one of the causes of the down-regulation of Nrg4 expression in obesity with chronic inflammatory response.