Department of Pediatric and Adolescents Medicine, Akershus University Hospital, Lørenskog, Norway.
Institute of Clinical Medicine, University of Oslo, Lørenskog, Norway.
Front Endocrinol (Lausanne). 2021 Dec 24;12:809916. doi: 10.3389/fendo.2021.809916. eCollection 2021.
Leptin, mainly secreted by fat cells, plays a core role in the regulation of appetite and body weight, and has been proposed as a mediator of metabolic programming. During pregnancy leptin is also secreted by the placenta, as well as being a key regulatory cytokine for the development, homeostatic regulation and nutrient transport within the placenta. South Asians have a high burden of type 2 diabetes, partly attributed to a "thin-fat-phenotype".
Our aim was to investigate how maternal ethnicity, adiposity and glucose- and lipid/cholesterol levels in pregnancy are related to placental leptin gene () DNA methylation.
We performed DNA methylation analyses of 13 placental CpG sites in 40 ethnic Europeans and 40 ethnic South Asians participating in the STORK-Groruddalen cohort.
South Asian ethnicity and gestational diabetes (GDM) were associated with higher placental methylation. The largest ethnic difference was found for CpG11 [5.8% (95% CI: 2.4, 9.2), p<0.001], and the strongest associations with GDM was seen for CpG5 [5.2% (1.4, 9.0), p=0.008]. Higher maternal LDL-cholesterol was associated with lower placental methylation, in particular for CpG11 [-3.6% (-5.5, -1.4) per one mmol/L increase in LDL, p<0.001]. After adjustments, including for nutritional factors involved in the one-carbon-metabolism cycle (vitamin D, B12 and folate levels), ethnic differences in placental methylation were strongly attenuated, while associations with glucose and LDL-cholesterol persisted.
Maternal glucose and lipid metabolism is related to placental methylation, whilst metabolic and nutritional factors largely explain a higher methylation level among ethnic South Asians.
瘦素主要由脂肪细胞分泌，在调节食欲和体重方面发挥核心作用，被认为是代谢编程的中介。在怀孕期间，胎盘也会分泌瘦素，同时也是胎盘发育、稳态调节和营养物质运输的关键调节细胞因子。南亚人患 2 型糖尿病的负担很重，部分原因是“瘦胖表型”。
我们旨在研究孕妇的种族、肥胖程度以及孕期血糖和血脂/胆固醇水平与胎盘瘦素基因（）DNA 甲基化的关系。
我们对参与 STORK-Groruddalen 队列的 40 名欧洲裔和 40 名南亚裔孕妇的 13 个胎盘 CpG 位点进行了 DNA 甲基化分析。
南亚裔种族和妊娠糖尿病（GDM）与较高的胎盘 甲基化有关。CpG11 差异最大[5.8%（95%CI：2.4，9.2），p<0.001]，与 GDM 最强的关联见于 CpG5[5.2%（1.4，9.0），p=0.008]。母亲 LDL 胆固醇水平升高与胎盘 甲基化水平降低有关，尤其是 CpG11[每增加一 mmol/L LDL，降低-3.6%（-5.5，-1.4），p<0.001]。调整包括涉及一碳代谢循环（维生素 D、B12 和叶酸水平）的营养因素后，胎盘 甲基化的种族差异明显减弱，而与血糖和 LDL 胆固醇的关联仍然存在。
母体的葡萄糖和脂质代谢与胎盘 甲基化有关，而代谢和营养因素在很大程度上解释了南亚裔种族中较高的甲基化水平。
