Associations between whole peripheral blood fatty acids and DNA methylation in humans.

Associations between whole peripheral blood fatty acids and DNA methylation in humans.
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DOI:
10.1038/srep25867
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发表时间:
2016-05-16
期刊:
影响因子:
4.6
通讯作者:
Lund G
Lund G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
de la Rocha C;Pérez-Mojica JE;León SZ;Cervantes-Paz B;Tristán-Flores FE;Rodríguez-Ríos D;Molina-Torres J;Ramírez-Chávez E;Alvarado-Caudillo Y;Carmona FJ;Esteller M;Hernández-Rivas R;Wrobel K;Wrobel K;Zaina S;Lund G

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脂肪酸(FA)在体外改变DNA甲基化,但有限的信息是在体内是否存在相应的协会,并反映任何短期的影响的饮食。在三个常规BMI类别中平均分布的哺乳期婴儿(LI; n = 49)和成年男性(AMM; n = 12)的血液中寻找整体DNA甲基化和FA之间的关联。AMM在单次西方饮食代表餐(餐后样本)或无餐(空腹样本)后8小时内以2小时间隔提供多个样本。在AMM中测定脂质/葡萄糖谱、HDAC 4启动子和PDK 4 5 'UTR甲基化。多元回归分析显示,全球(LI)和全球和PDK 4特异性DNA甲基化(AMM)与二十碳五烯酸和花生四烯酸呈正相关。HDAC 4甲基化与AMM患者餐后花生四烯酸呈负相关。整体DNA甲基化没有显示出任何明确的日内模式,表明对饮食的短期反应。尽管如此,总体DNA甲基化在正常体重受试者餐后和空腹时均较高,并且与相对于单不饱和和饱和脂肪酸的较高多不饱和脂肪酸相一致。我们首次在两个不同年龄、饮食和出生后发育阶段的人群中显示了DNA甲基化与特定FA的强相关性。
Fatty acids (FA) modify DNA methylation in vitro, but limited information is available on whether corresponding associations exist in vivo and reflect any short-term effect of the diet. Associations between global DNA methylation and FAs were sought in blood from lactating infants (LI; n = 49) and adult males (AMM; n = 12) equally distributed across the three conventional BMI classes. AMM provided multiple samples at 2-hour intervals during 8 hours after either a single Western diet-representative meal (post-prandial samples) or no meal (fasting samples). Lipid/glucose profile, HDAC4 promoter and PDK4 5’UTR methylation were determined in AMM. Multiple regression analysis revealed that global (in LI) and both global and PDK4-specific DNA methylation (in AMM) were positively associated with eicosapentaenoic and arachidonic acid. HDAC4 methylation was inversely associated with arachidonic acid post-prandially in AMM. Global DNA methylation did not show any defined within-day pattern that would suggest a short-term response to the diet. Nonetheless, global DNA methylation was higher in normal weight subjects both post-prandially and in fasting and coincided with higher polyunsaturated relative to monounsaturated and saturated FAs. We show for the first time strong associations of DNA methylation with specific FAs in two human cohorts of distinct age, diet and postnatal development stage.