Maternal fat intake in rats alters 20:4n-6 and 22:6n-3 status and the epigenetic regulation of Fads2 in offspring liver.

Maternal fat intake in rats alters 20:4n-6 and 22:6n-3 status and the epigenetic regulation of Fads2 in offspring liver.
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DOI:
10.1016/j.jnutbio.2012.09.005
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发表时间:
2013-07
期刊:
The Journal of nutritional biochemistry
影响因子:
--
通讯作者:
Burdge GC
Burdge GC
中科院分区:
其他
文献类型:
--
作者:
Hoile SP;Irvine NA;Kelsall CJ;Sibbons C;Feunteun A;Collister A;Torrens C;Calder PC;Hanson MA;Lillycrop KA;Burdge GC

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不良的产前营养,通过表观遗传过程,导致后代表型的持续变化。我们研究了母体脂肪摄入对成年子代多不饱和脂肪酸状态以及编码Δ-6去饱和酶(多不饱和脂肪酸合成的速率限制)的FADS2表观遗传调控的影响。大鼠(每组6只)从妊娠前14天起至断奶前分别饲喂3.5%(w/w)、7%(w/w)或21%(w/w)的黄油或鱼油(FO)。仔鼠(每组6只雄性和雌性)饲喂4%(w/w)豆油,直到出生后第77天。肝脏磷脂酰胆碱、卵磷脂乙醇胺和血浆磷脂酰胆碱的20:4n-6和22:6n-3水平在饲喂21%脂肪和3.5%或7%脂肪的仔鼠中均低于3.5%和7%脂肪。肝脏Fads2的表达与母亲的膳食脂肪呈负相关。FADS2信使核糖核酸的表达与−623、−394、−84和−76碱基相对于转录起始点的甲基化呈负相关(均P<0.005)。在饲喂21%脂肪的母鸡后代中,这些CPGS的甲基化程度高于3.5%和7%的脂肪;FO高于黄油。饲喂7%脂肪饲料的成年雌性大鼠肝脏PC和FADS2表达的20:4N-6状态降低,CpGS−623、−394、−84和−76的甲基化增加,而在7%到4%脂肪饲料的动物中,这一现象正好相反。这些发现表明,发育过程中的脂肪暴露通过Fads2的表观遗传调节导致子代肝脏PUFA状态的持续性变化,而成年鼠则表现出短暂的反应。因此,Fads2的表观遗传调控可能有助于PUFA合成的短期和长期调控。
Poor prenatal nutrition, acting through epigenetic processes, induces persistent changes in offspring phenotype. We investigated the effect of maternal fat intake on polyunsaturated fatty acid (PUFA) status and on the epigenetic regulation of Fads2, encoding Δ6 desaturase (rate limiting in PUFA synthesis), in the adult offspring. Rats (n=6 per dietary group) were fed either 3.5% (w/w), 7% (w/w) or 21% (w/w) butter or fish oil (FO) from 14 days preconception until weaning. Offspring (n=6 males and females per dietary group) were fed 4% (w/w) soybean oil until postnatal day 77. 20:4n-6 and 22:6n-3 levels were lower in liver phosphatidylcholine (PC) and phosphatidylethanolamine and plasma PC (all P<.0001) in offspring of dams fed 21% than 3.5% or 7% fat regardless of type. Hepatic Fads2 expression related inversely to maternal dietary fat. Fads2 messenger RNA expression correlated negatively with methylation of CpGs at −623, −394, −84 and −76 bases relative to the transcription start site (all P<.005). Methylation of these CpGs was higher in offspring of dams fed 21% than 3.5% or 7% fat; FO higher than butter. Feeding adult female rats 7% fat reduced 20:4n-6 status in liver PC and Fads2 expression and increased methylation of CpGs −623, −394, −84 and −76 that reversed in animals switched from 7% to 4% fat diets. These findings suggest that fat exposure during development induces persistent changes, while adults exhibit a transient response, in hepatic PUFA status in offspring through epigenetic regulation of Fads2. Thus, epigenetic regulation of Fads2 may contribute to short- and long-term regulation of PUFA synthesis.
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