Department of Endocrinology and Nephrology, University of Leipzig, 04103 Leipzig, Germany; Leipzig University Medical Center, IFB Adiposity Diseases, 04103 Leipzig, Germany.
Department of Endocrinology and Nephrology, University of Leipzig, 04103 Leipzig, Germany.
Diabetes Metab. 2018 Mar;44(2):150-154. doi: 10.1016/j.diabet.2017.06.001. Epub 2017 Jul 11.
Neuregulin 4 has recently been recognized as a novel adipokine secreted by brown adipose tissue (BAT), with beneficial effects on murine insulin resistance and hepatic steatosis. Yet, thus far, neither regulation of neuregulin 4 in gestational diabetes mellitus (GDM) nor its longitudinal changes in the peripartum period have been elucidated.
Circulating neuregulin 4 levels were measured by ELISA in 74 women with GDM and 74 healthy, gestational-age-matched controls. Also, neuregulin 4 was quantified during pregnancy and compared with postpartum levels in a follow-up study of 25 women with previous GDM and 25 healthy control women.
Women with GDM had lower median serum levels of the novel BAT-secreted adipokine neuregulin 4 (3.0μg/L) compared with healthy (non-GDM) pregnant controls (3.5μg/L; P=0.020), and the area under the glucose curve (AUC) was an independent and negative predictor of circulating neuregulin 4 (P=0.033). Also, median postpartum serum concentrations of neuregulin 4 (3.2μg/L) were not significantly different from prepartum levels (2.8μg/L; P=0.328). In addition, neuregulin 4 was positively and independently associated with irisin (P=0.009), but not other BAT-secreted adipokines.
CONCLUSION/INTERPRETATION: Women with GDM have significantly lower circulating neuregulin 4 levels compared with healthy pregnant controls, and the AUC is negatively and independently associated with neuregulin 4 during pregnancy. Neuregulin 4 is positively correlated with irisin during pregnancy, as well as in a longitudinal fashion. Future studies are now needed to better elucidate the precise pathomechanisms of the regulation of BAT-secreted adipokines during pregnancy.
神经调节蛋白 4 最近被认为是一种由棕色脂肪组织（BAT）分泌的新型脂肪因子，对小鼠胰岛素抵抗和肝脂肪变性具有有益作用。然而，迄今为止，妊娠期糖尿病（GDM）中神经调节蛋白 4 的调节及其在围产期的纵向变化尚未阐明。
采用 ELISA 法检测 74 例 GDM 妇女和 74 例健康、孕龄匹配对照者的循环神经调节蛋白 4 水平。此外，在 25 例既往 GDM 妇女和 25 例健康对照妇女的随访研究中，比较了孕期和产后的神经调节蛋白 4 水平。
GDM 妇女的新型 BAT 分泌脂肪因子神经调节蛋白 4 的血清水平中位数（3.0μg/L）低于健康（非 GDM）妊娠对照组（3.5μg/L；P=0.020），血糖曲线下面积（AUC）是循环神经调节蛋白 4 的独立负性预测因子（P=0.033）。此外，产后血清神经调节蛋白 4 中位数（3.2μg/L）与产前水平（2.8μg/L；P=0.328）无显著差异。此外，神经调节蛋白 4 与鸢尾素呈正相关（P=0.009），但与其他 BAT 分泌脂肪因子无相关性。
结论/解释：与健康妊娠对照组相比，GDM 妇女的循环神经调节蛋白 4 水平明显降低，AUC 在妊娠期间与神经调节蛋白 4 呈负相关且独立相关。神经调节蛋白 4 在妊娠期间与鸢尾素呈正相关，且呈纵向相关。目前需要进一步的研究来更好地阐明妊娠期间 BAT 分泌脂肪因子调节的确切病理机制。
