Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI, USA; Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, USA.
Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI, USA.
Mol Cell Endocrinol. 2020 Apr 5;505:110739. doi: 10.1016/j.mce.2020.110739. Epub 2020 Jan 29.
Maternal diet is an important factor in prenatal development that also has implications for disease risk later in life. The adipokine leptin is a key regulator of energy homeostasis and may be involved in the association between maternal nutrition, maternal obesity, and infant outcomes. DNA methylation of placenta genes may occur in response to exposures and may program subsequent infant development. This study examined maternal diet, placenta leptin gene DNA methylation, and neonatal growth in a sample of healthy neonates and their mothers.
Mothers and their healthy neonates (N = 135) were recruited within 1-2 days following delivery at Women and Infants Hospital in Providence, RI. A structured interview was conducted to assess maternal dietary intake. Maternal pre-pregnancy weight, weight gain during pregnancy, maternal health, medications, and vitamin use were obtained from medical records. Bisulfite pyrosequencing was used to measure methylation of CpG sites in the promoter region of the placenta leptin gene and determine genotype of the leptin single nucleotide polymorphism (SNP) rs2167270, which is known to influence leptin methylation. Bivariate analyses and linear regression models were used to evaluate associations of demographics, diet, and mean leptin methylation.
Genotype was a significant predictor of placenta leptin DNA methylation (p < .01), and after controlling for this and other relevant maternal and infant covariates, lower levels of leptin methylation were significantly associated with greater intake of carbohydrates (p < .05), in particular added sugars (p < .05) and white/refined carbohydrates (p < .05). Total caloric intake was also associated with placenta leptin methylation (p < .05), however after controlling for relevant covariates, significance diminished to trend-level. There were no significant associations of placenta leptin methylation and intake of protein (p > .05) or fat (p > .05).
These findings underline the importance of intake of carbohydrate consumption for methylation of the placenta leptin gene. Because methylation reduces gene transcription, lower methylation may indicate a placenta response to high caloric intake and carbohydrate food that would result in higher levels of this hormone during fetal development. Further investigation of the developmental ramifications of epigenetic changes to placenta leptin methylation should be pursued.
母体饮食是胎儿发育的一个重要因素，也与生命后期的疾病风险有关。脂肪细胞因子瘦素是能量平衡的关键调节剂，可能与母体营养、母体肥胖和婴儿结局之间的关联有关。胎盘基因的 DNA 甲基化可能是对暴露的反应，并可能影响随后的婴儿发育。本研究在罗德岛州普罗维登斯妇女和婴儿医院的健康新生儿及其母亲的样本中研究了母体饮食、胎盘瘦素基因 DNA 甲基化和新生儿生长。
在罗得岛普罗维登斯妇女和婴儿医院分娩后 1-2 天内，招募母亲及其健康新生儿（N=135）。通过结构化访谈评估了母亲的饮食摄入情况。从病历中获得了母亲的孕前体重、孕期体重增加、母亲健康状况、药物使用和维生素使用情况。使用亚硫酸氢盐焦磷酸测序来测量胎盘瘦素基因启动子区域的 CpG 位点的甲基化，并确定瘦素单核苷酸多态性（SNP）rs2167270 的基因型，该 SNP 已知会影响瘦素甲基化。使用双变量分析和线性回归模型评估了人口统计学、饮食和平均瘦素甲基化的关联。
基因型是胎盘瘦素 DNA 甲基化的显著预测因子（p<0.01），在控制了这一因素和其他相关的母婴变量后，瘦素甲基化水平与碳水化合物（尤其是添加糖，p<0.05）和白/精制碳水化合物（p<0.05）的摄入量呈显著负相关。总热量摄入也与胎盘瘦素甲基化相关（p<0.05），但在控制了相关协变量后，其显著性降低至趋势水平。胎盘瘦素甲基化与蛋白质（p>0.05）或脂肪（p>0.05）的摄入量无显著关联。
这些发现强调了碳水化合物摄入对胎盘瘦素基因甲基化的重要性。因为甲基化会降低基因转录，所以较低的甲基化可能表明胎盘中对高热量和碳水化合物食物的反应，这将导致在胎儿发育过程中这种激素的水平升高。应进一步研究胎盘瘦素甲基化的表观遗传变化对发育的影响。
