Methyl Donor Supplementation Blocks the Adverse Effects of Maternal High Fat Diet on Offspring Physiology
Methyl Donor Supplementation Blocks the Adverse Effects of Maternal High Fat Diet on Offspring Physiology
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DOI：
10.1371/journal.pone.0063549
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发表时间：
2013-05-02
期刊：
影响因子：
3.7
通讯作者：
Reyes, Teresa M.
中科院分区：
文献类型：
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作者：
Carlin, JesseLea;George, Robert;Reyes, Teresa M.
孕期母亲摄入高脂肪饮食会增加后代肥胖的风险。我们之前利用小鼠模型表明，母亲摄入高脂肪（60%）饮食会导致后代大脑中DNA甲基化的整体和基因特异性降低。本实验旨在尝试通过在母亲饮食中补充甲基供体来逆转这种DNA低甲基化，并确定甲基供体补充是否能够阻止或减轻与母亲摄入高脂肪饮食相关的表型。对成年雄性和雌性后代的代谢和行为（脂肪偏好）结果进行了评估。测量了大脑中μ-阿片受体和多巴胺转运体mRNA的表达以及整体DNA甲基化情况。在母亲饮食中补充甲基供体减轻了高脂肪饮食母鼠的后代中出现的一些不良影响的发展，包括体重增加、脂肪偏好增加（雄性）、中枢神经系统基因表达的变化以及前额叶皮质的整体低甲基化。观察到了显著的性别差异。这些发现确定了孕期平衡的甲基化状态的重要性，特别是在母亲摄入高脂肪饮食的情况下，对于后代的最佳结果至关重要。
Maternal consumption of a high fat diet during pregnancy increases the offspring risk for obesity. Using a mouse model, we have previously shown that maternal consumption of a high fat (60%) diet leads to global and gene specific decreases in DNA methylation in the brain of the offspring. The present experiments were designed to attempt to reverse this DNA hypomethylation through supplementation of the maternal diet with methyl donors, and to determine whether methyl donor supplementation could block or attenuate phenotypes associated with maternal consumption of a HF diet. Metabolic and behavioral (fat preference) outcomes were assessed in male and female adult offspring. Expression of the mu-opioid receptor and dopamine transporter mRNA, as well as global DNA methylation were measured in the brain. Supplementation of the maternal diet with methyl donors attenuated the development of some of the adverse effects seen in offspring from dams fed a high fat diet; including weight gain, increased fat preference (males), changes in CNS gene expression and global hypomethylation in the prefrontal cortex. Notable sex differences were observed. These findings identify the importance of balanced methylation status during pregnancy, particularly in the context of a maternal high fat diet, for optimal offspring outcome.