In utero exposure to a maternal high-fat diet alters the epigenetic histone code in a murine model.
In utero exposure to a maternal high-fat diet alters the epigenetic histone code in a murine model.
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DOI：
10.1016/j.ajog.2014.01.045
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发表时间：
2014-05
影响因子：
9.8
通讯作者：
Aagaard, Kjersti M.
中科院分区：
文献类型：
--
作者：
Suter, Melissa A.;Ma, Jun;Vuguin, Patricia M.;Hartil, Kirsten;Fiallo, Ariana;Harris, R. Alan;Charron, Maureen J.;Aagaard, Kjersti M.
来自动物模型的数据显示，在子宫内暴露于母体高脂肪饮食（HFD）使得这些后代对成年代谢综合征的发病易感。我们和其他人先前已经表明，组蛋白的表观遗传修饰可能作为子宫内暴露的分子记忆，导致成人疾病的风险。由于野生型（WT）母亲所生的GLUT 4（胰岛素敏感性葡萄糖转运蛋白）杂合子小鼠在子宫内暴露于高脂肪饮食时表现出代谢综合征，因此我们试图分析易感后代胎儿肝脏中发生的全基因组表观遗传变化。研究了WT母亲在子宫内暴露于对照或HF饮食的WT和Glut 4 +/−（G4+/−）后代。免疫印迹法用于测量胎儿和5周动物的肝组蛋白修饰。染色质免疫沉淀（ChIP），然后杂交到芯片阵列（ChIP芯片）被用来检测组蛋白修饰的全基因组变化与HFD曝光。我们发现，肝H3 K14 ac和H3 K9 me 3的水平显着增加与HFD暴露在WT和G4+/−胎儿和5周的后代。我们的ChIP芯片数据的途径分析揭示了沿着调节脂质代谢的途径的差异H3 K14 ac和H3 K9 me 3富集沿着，特别是在Pparg、Ppara、Rxra和Rora的启动子区域中。我们得出结论，子宫内HFD暴露与WT和G4+/−后代中胎肝组蛋白修饰的功能改变相关，其中一些持续至5周龄。
Data from animal models show that in utero exposure to a maternal high fat diet (HFD) renders susceptibility of these offspring to the adult onset of metabolic syndrome. We and others have previously shown that epigenetic modifications to histones may serve as a molecular memory of the in utero exposure, rendering risk of adult disease. Because mice heterozygous for GLUT4 (insulin sensitive glucose transporter) born to wild-type (WT) mothers demonstrate exacterbated metabolic syndrome when exposed to a high fat diet in utero, we sought to analyze the genome-wide epigenetic changes which occur in the fetal liver in susceptible offspring. WT and Glut4+/− (G4+/−) offspring of WT mothers exposed either to a control or a HF diet in utero were studied. Immunoblotting was used to measure hepatic histone modifications of fetal and 5 week animals. Chromatin immunoprecipitation (ChIP) followed by hybridization to chip arrays (ChIP on chip) was utilized to detect genome-wide changes of histone modifications with HFD exposure. We found that levels of hepatic H3K14ac and H3K9me3 significantly increased with HFD exposure in WT and G4+/− fetal and 5 week offspring. Pathway analysis of our ChIP on chip data reveal differential H3K14ac and H3K9me3 enrichment along pathways which regulate lipid metabolism, specifically in the promoter regions of Pparg, Ppara, Rxra and Rora. We conclude that HFD exposure in utero is associated with functional alterations to fetal hepatic histone modifications in both WT and G4+/− offspring, some which persist up to 5 weeks of age.
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