High folate gestational and post-weaning diets alter hypothalamic feeding pathways by DNA methylation in Wistar rat offspring
High folate gestational and post-weaning diets alter hypothalamic feeding pathways by DNA methylation in Wistar rat offspring
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DOI：
10.4161/epi.24948
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发表时间：
2013-07-01
期刊：
影响因子：
3.7
通讯作者：
Anderson, G. Harvey
中科院分区：
文献类型：
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作者：
Cho, Clara E.;Sanchez-Hernandez, Diana;Anderson, G. Harvey
过量的维生素，特别是叶酸，在怀孕期间被消耗，但对后代的后期影响尚不清楚。高多种维生素（10倍AIN-93 G，HV）妊娠饮食会增加Wistar大鼠后代代谢综合征的特征。我们假设叶酸，一种在DNA甲基化中具有活性的维生素，通过食物摄入调节基因的表观遗传修饰来解释这些效应。在妊娠期间喂食10倍叶酸（HFol）饮食并断奶至推荐维生素（RV）或HFol饮食的母鼠的雄性后代与RV母鼠出生并断奶至RV饮食29周的雄性后代进行比较。喂食RV饲料的HFol母鼠后代的摄食量和体重最高。相比之下，HFol母鼠后代的HFol幼鼠饮食减少了食物摄入（7%，p = 0.02）、体重（9%，p = 0.03）和对葡萄糖负荷的葡萄糖反应（21%，p = 0.02），并改善了对胰岛素负荷的葡萄糖反应（20%，p = 0.009）。HFol单独在妊娠期或幼鼠饮食中改变了喂养相关神经肽的基因表达。前阿黑皮素（POMC）启动子的低甲基化发生在HFol幼鼠饮食中。POMC特异性甲基化与葡萄糖对葡萄糖负荷的反应呈正相关（r = 0.7，p = 0.03）。总之，来自喂食HFol妊娠期饮食的母鼠的后代的致肥胖表型可以通过喂食HFol饮食来纠正。我们的工作是新颖的，显示断奶后下丘脑的表观遗传可塑性，并在子宫内编程维生素妊娠饮食可以修改的维生素含量的幼犬饮食。
Excess vitamins, especially folate, are consumed during pregnancy but later-life effects on the offspring are unknown. High multivitamin (10-fold AIN-93G, HV) gestational diets increase characteristics of metabolic syndrome in Wistar rat offspring. We hypothesized that folate, the vitamin active in DNA methylation, accounts for these effects through epigenetic modification of food intake regulatory genes. Male offspring of dams fed 10-fold folate (HFol) diet during pregnancy and weaned to recommended vitamin (RV) or HFol diets were compared with those born to RV dams and weaned to RV diet for 29 weeks. Food intake and body weight were highest in offspring of HFol dams fed the RV diet. In contrast, the HFol pup diet in offspring of HFol dams reduced food intake (7%, p = 0.02), body weight (9%, p = 0.03) and glucose response to a glucose load (21%, p = 0.02), and improved glucose response to an insulin load (20%, p = 0.009). HFol alone in either gestational or pup diet modified gene expression of feeding-related neuropeptides. Hypomethylation of the pro-opiomelanocortin (POMC) promoter occurred with the HFol pup diet. POMC-specific methylation was positively associated with glucose response to a glucose load (r = 0.7, p = 0.03). In conclusion, the obesogenic phenotype of offspring from dams fed the HFol gestational diet can be corrected by feeding them a HFol diet. Our work is novel in showing post-weaning epigenetic plasticity of the hypothalamus and that in utero programming by vitamin gestational diets can be modified by vitamin content of the pup diet.