McKay Jill A, Xie Long, Adriaens Michiel, Evelo Chris T, Ford Dianne, Mathers John C
Human Nutrition Research Centre, Institute for Health and Society, Newcastle University, UK.
Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, UK.
Mol Nutr Food Res. 2017 Apr;61(4). doi: 10.1002/mnfr.201600713. Epub 2017 Feb 6.
The 'Predictive Adaptive Response' hypothesis suggests that the in utero environment when mismatched with the post-natal environment can influence later life health. Underlying mechanisms are poorly understood, but may involve gene transcription changes regulated via epigenetic mechanisms.
In a 2 × 2 factorial design, female C57Bl/6 mice were randomised to low or normal folate diets (0.4 mg/2 mg folic acid/kg diet) prior to and during pregnancy and lactation with offspring randomised to high- or low-fat diets at weaning. Genome-wide gene expression and promoter DNA methylation were measured using microarrays in adult male livers. Maternal folate depletion and high fat intake post-weaning influenced gene expression (1859 and 1532 genes, respectively) and promoter DNA methylation (201 and 324 loci, respectively) but changes in expression and methylation were poorly matched for both dietary interventions. Expression of 642 genes was altered in response to both maternal folate depletion and post-weaning high fat feeding, treatments imposed separately. In addition, there was evidence that the combined dietary insult (i.e. maternal folate depletion followed by high fat post-weaning) caused the largest expression change for most genes.
Our observations align with, and provide evidence in support of, a potential underlying mechanism for the 'Predictive Adaptive Response' hypothesis.
“预测性适应反应”假说表明，子宫内环境若与出生后环境不匹配，可能会影响后期健康。其潜在机制尚不清楚，但可能涉及通过表观遗传机制调节的基因转录变化。
采用2×2析因设计，将雌性C57Bl/6小鼠在怀孕和哺乳前及期间随机分为低叶酸或正常叶酸饮食组（0.4毫克/2毫克叶酸/千克饮食），子代在断奶时随机分为高脂肪或低脂肪饮食组。使用微阵列测量成年雄性肝脏中的全基因组基因表达和启动子DNA甲基化。母体叶酸缺乏和断奶后高脂肪摄入分别影响基因表达（分别为1859个和1532个基因）和启动子DNA甲基化（分别为201个和324个位点），但两种饮食干预的表达和甲基化变化匹配度较差。单独施加的母体叶酸缺乏和断奶后高脂肪喂养这两种处理，均使642个基因的表达发生改变。此外，有证据表明，联合饮食损伤（即母体叶酸缺乏后断奶后高脂肪喂养）导致大多数基因的表达变化最大。
我们的观察结果与“预测性适应反应”假说的潜在机制相符，并提供了支持证据。
