Prepregnancy maternal diabetes combined with obesity impairs placental mitochondrial function involving Nrf2/ARE pathway and detrimentally alters metabolism of offspring
Prepregnancy maternal diabetes combined with obesity impairs placental mitochondrial function involving Nrf2/ARE pathway and detrimentally alters metabolism of offspring
复制标题
DOI：
10.1016/j.orcp.2017.01.002
复制
发表时间：
2018-01-01
影响因子：
4.3
通讯作者：
Liu, Geli
中科院分区：
文献类型：
--
作者：
Duan, Yang;Sun, Fuqiang;Liu, Geli
代谢紊乱通常会增加活性氧 (ROS) 水平并损害线粒体功能。胎盘向胎儿提供营养和激素信号以调节胎儿的新陈代谢，但也容易受到氧化剂的损伤。本研究的目的是确定母亲已有 2 型糖尿病 (DM) 合并肥胖对胎盘线粒体功能和后代代谢紊乱的影响。该研究纳入了 96 名孕妇。这些女性被分为以下几组：健康女性（对照组，n = 24）、患有糖尿病的女性（DM，n = 24）、肥胖女性（OB，n = 24）以及患有糖尿病和肥胖的女性（DM + OB，n = 24）。测量四组胎盘的ROS水平、线粒体含量和线粒体呼吸复合物活性。免疫荧光染色和Western blotting检测核因子红细胞2相关因子2（Nrf2）和血红素加氧酶-1（HO-1）的表达。此外，还测量了其后代的胰岛素、葡萄糖、瘦素、非酯化脂肪酸（NEFA）、脂联素和甘油三酯的血清水平。与对照组和DM组胎盘相比，合并肥胖的母体DM胎盘中ROS水平显着升高，线粒体DNA（mtDNA）含量和线粒体呼吸复合物I、II-III活性降低。母亲糖尿病合并肥胖显着降低 Nrf2 和 HO-1 表达。此外，母亲糖尿病与肥胖相结合影响了后代的葡萄糖和脂质代谢。总之，患有 DM 和肥胖症的女性会不利地改变胎盘在氧化应激调节中的功能，并且涉及 Nrf2/ARE（抗氧化反应元件）途径。这可能会增加其后代代谢紊乱的易感性。 (C) 2017 年亚洲大洋洲肥胖研究协会。由爱思唯尔有限公司出版。保留所有权利。
Metabolic disorders usually increase the level of reactive oxygen species (ROS) and damage mitochondrial function. The placenta supplies nutrients and hormonal signals to the fetus for regulating fetal metabolism, and is also prone to injury by oxidants. The aim of this study was to determine the effect of pre-existing maternal type 2 diabetes mellitus (DM) combined with obesity on placental mitochondrial function and metabolism disorders of offspring. The study included 96 pregnant women. The women were put into the following groups: healthy women (control, n = 24), women with DM (DM, n =24), women with obesity (OB, n =24) and women with both DM and obesity (DM + OB, n = 24). The ROS level, mitochondrial content, and the mitochondrial respiratory complex activities of the placenta were measured in the four groups. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was detected by immunofluorescence staining and western blotting. In addition, serum levels of insulin, glucose, leptin, nonesterified fatty acid (NEFA), adiponectin and triglycerides of their offspring were also measured. Maternal DM combined with obesity markedly increased ROS level, reduced mitochondrial DNA (mtDNA) content and mitochondrial respiratory complex I, II-III activities in placenta compared to the placenta from the control group and the DM group. Maternal DM combined with obesity significantly decreased Nrf2 and HO-1 expression. Furthermore, maternal DM combined with obesity influenced the glucose and lipid metabolism in their offspring. In conclusion, women with both DM and obesity detrimentally alter placenta function in oxidative stress regulation, and the Nrf2/ARE (antioxidant responsive element) pathway is involved. This may increase metabolic disturbance susceptibility in their offspring. (C) 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.