Department of Foods and Nutrition, University of Georgia, Athens, GA, USA.
Department of Foods and Nutrition, University of Georgia, Athens, GA, USA.
Obes Res Clin Pract. 2017 Nov-Dec;11(6):665-676. doi: 10.1016/j.orcp.2017.06.004. Epub 2017 Jul 18.
BACKGROUND/OBJECTIVES: Obesity and maternal folate deficiency are associated with increased risk for neural tube defects (NTDs). Limited knowledge exists on the impact of folate status or obesity on DNA methylation of genes related to NTD risk and folate metabolism.
SUBJECTS/METHODS: Women (18-35y) with normal weight (NW; BMI 18.5-24.9kg/m; n=12) and obesity (OB; BMI >30kg/m; n=6) were provided FA (800μg/d) for 8-weeks. Serum folate concentration and changes in DNA methylation across 2098 CpG sites in 91 genes related to NTD risk and folate metabolism were examined.
Serum folate concentration increased in both groups following FA supplementation, but OB maintained a relative lower concentration (NW; 38.36±2.50-71.41±3.02nmol/L and OB; 27.12±3.09-56.85±3.90nmol/L). Methylation of 56 and 99 CpG sites changed in response to supplementation in NW and OB, respectively, and majority of these sites decreased in methylation in both groups. Only 4 CpG sites responded to supplementation in both groups. Gene ontology analysis revealed a response to supplementation in 61 biological processes (BPs) from the selected genes. Five of the 61 BPs were identified only in NW, including neural tube closure, while 13 of the 61 BPs were enriched only in OB, including folate metabolism, vitamin B12 metabolism and methylation related processes.
Changes in DNA methylation in genes related to NTD risk and folate metabolism in response to FA supplementation were different in NW and OB. Increased NTD risk and abnormal folate metabolism in obesity may be due to a distinctive epigenetic response to folate status in these genes.
背景/目的：肥胖和母体叶酸缺乏与神经管缺陷（NTD）风险增加有关。目前对于叶酸状态或肥胖对与 NTD 风险和叶酸代谢相关的基因的 DNA 甲基化的影响知之甚少。
受试者/方法：将体重正常（NW；BMI 18.5-24.9kg/m；n=12）和肥胖（OB；BMI>30kg/m；n=6）的女性（18-35 岁）提供 FA（800μg/d）补充 8 周。检测了与 NTD 风险和叶酸代谢相关的 91 个基因中的 2098 个 CpG 位点的血清叶酸浓度和 DNA 甲基化变化。
两组人群在 FA 补充后血清叶酸浓度均增加，但 OB 仍保持相对较低的浓度（NW；38.36±2.50-71.41±3.02nmol/L 和 OB；27.12±3.09-56.85±3.90nmol/L）。NW 和 OB 中分别有 56 和 99 个 CpG 位点的甲基化对补充有反应，并且大多数这些位点的甲基化在两组中均降低。两组仅 4 个 CpG 位点对补充有反应。基因本体分析显示，从选定基因中，有 61 个生物学过程（BPs）对补充有反应。在 NW 中鉴定出 5 个仅存在于 NW 中的 BPs，包括神经管闭合，而在 OB 中鉴定出 13 个仅存在于 OB 中的 BPs，包括叶酸代谢、维生素 B12 代谢和甲基化相关过程。
NW 和 OB 中，FA 补充对与 NTD 风险和叶酸代谢相关的基因的 DNA 甲基化变化不同。肥胖中 NTD 风险增加和叶酸代谢异常可能是由于这些基因中叶酸状态的独特表观遗传反应所致。
