Supplementation with N-3 long-chain polyunsaturated fatty acids or olive oil in men and women with renal disease induces differential changes in the DNA methylation of FADS2 and ELOVL5 in peripheral blood mononuclear cells.
Supplementation with N-3 long-chain polyunsaturated fatty acids or olive oil in men and women with renal disease induces differential changes in the DNA methylation of FADS2 and ELOVL5 in peripheral blood mononuclear cells.
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在肾脏疾病的男性和女性中补充N-3长链多不饱和脂肪酸或橄榄油会引起外周血单核细胞中FADS2和ElOVL5的DNA甲基化的差异变化。
DOI：
10.1371/journal.pone.0109896
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Burdge GC
中科院分区：
文献类型：
--
作者：
Hoile SP;Clarke-Harris R;Huang RC;Calder PC;Mori TA;Beilin LJ;Lillycrop KA;Burdge GC
在动物模型和培养细胞中的研究表明，脂肪酸可以诱导特定基因的DNA甲基化改变。目前还没有关于补充脂肪酸对成年人基因表观遗传调控的影响的研究。我们研究了肾脏病患者每天补充4 g n-3长链多不饱和脂肪酸（n-3 LCPUFA）或橄榄油（OO）8周对男性和女性（年龄53 - 63岁）外周血单核细胞PUFA生物合成相关基因5′调控区单个CpG位点甲基化状态的影响。OO和n-3 LCPUFA分别改变（甲基化差异>10%）2/22脂肪酸去饱和酶（FADS）-2 CpG，而n-3 LCPUFA，但不是OO，改变（>10%）1/12男性中的VL 5 CpG。OO改变了（>6%）8/22个FADS 2 CpG和（>3%）3/12个延长酶（VL）-5 CpG，而在女性中，n-3 LCPUFA改变了（>5%）3/22个FADS 2 CpG和2/12个（>3%）LCPVL 5 CpG。FADS 1或FADVL 2甲基化没有改变。补充n-3 PUFA的结果在健康成年人（23至30岁）的血液DNA中得到了复制。FADS 2和FADVVL 5中改变的CpG的甲基化状态与其转录物的水平负相关。这些发现表明，适量的脂肪酸补充剂可以诱导成年人特定CpG位点的甲基化改变，这取决于补充剂的性质和性别。这对于理解脂肪酸对PUFA代谢和细胞功能的影响具有意义。
Studies in animal models and in cultured cells have shown that fatty acids can induce alterations in the DNA methylation of specific genes. There have been no studies of the effects of fatty acid supplementation on the epigenetic regulation of genes in adult humans. We investigated the effect of supplementing renal patients with 4 g daily of either n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) or olive oil (OO) for 8 weeks on the methylation status of individual CpG loci in the 5′ regulatory region of genes involved in PUFA biosynthesis in peripheral blood mononuclear cells from men and women (aged 53 to 63 years). OO and n-3 LCPUFA each altered (>10% difference in methylation) 2/22 fatty acid desaturase (FADS)-2 CpGs, while n-3 LCPUFA, but not OO, altered (>10%) 1/12 ELOVL5 CpGs in men. OO altered (>6%) 8/22 FADS2 CpGs and (>3%) 3/12 elongase (ELOVL)-5 CpGs, while n-3 LCPUFA altered (>5%) 3/22 FADS2 CpGs and 2/12 (>3%) ELOVL5 CpGs in women. FADS1 or ELOVL2 methylation was unchanged. The n-3 PUFA supplementation findings were replicated in blood DNA from healthy adults (aged 23 to 30 years). The methylation status of the altered CpGs in FADS2 and ELOVL5 was associated negatively with the level of their transcripts. These findings show that modest fatty acid supplementation can induce altered methylation of specific CpG loci in adult humans, contingent on the nature of the supplement and on sex. This has implications for understanding the effect of fatty acids on PUFA metabolism and cell function.
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影响因子：
4.1
作者：
GARG, ML;SEBOKOVA, E;CLANDININ, MT
通讯作者：
CLANDININ, MT
影响因子：
4.8
作者：
Devlin, Angela M.;Singh, Ranji;Lentz, Steven R.
通讯作者：
Lentz, Steven R.
影响因子：
4.2
作者：
Burdge, Graham C.;Lillycrop, Karen A.;Hanson, Mark A.
通讯作者：
Hanson, Mark A.
影响因子：
64.5
作者：
Goldberg, Aaron D.;Allis, C. David;Bernstein, Emily
通讯作者：
Bernstein, Emily
影响因子：
12.3
作者：
Burdge, Graham C.;Lillycrop, Karen A.
通讯作者：
Lillycrop, Karen A.