Maternal fructose consumption down-regulates Lxra expression via miR-206-mediated regulation.
Maternal fructose consumption down-regulates Lxra expression via miR-206-mediated regulation.
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DOI：
10.1016/j.jnutbio.2020.108386
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发表时间：
2020-04
期刊：
影响因子：
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通讯作者：
Mirai Yamazaki;Eiji Munetsuna;Hiroya Yamada;Y. Ando;Genki Mizuno;R. Fujii;Yuki Nouchi;Itsuki Kageyama-Itsuk
中科院分区：
文献类型：
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作者：
Mirai Yamazaki;Eiji Munetsuna;Hiroya Yamada;Y. Ando;Genki Mizuno;R. Fujii;Yuki Nouchi;Itsuki Kageyama-Itsuk
母亲摄入果糖会影响后代晚年的新陈代谢功能。然而，其分子机制仍然知之甚少。MicroRNA表达谱和DNA甲基化状态的差异是解释导致代谢紊乱发展的发育编程的一个候选机制。这项研究从表观遗传修饰的角度考察了母亲摄入果糖的跨代效应。为此，我们收集了孕期和哺乳期接触母体蒸馏水或20%果糖水的雄性子代大鼠的血清和肝组织。果糖喂养的母鼠出生后第160天，血清高密度脂蛋白胆固醇(HDLC)水平下降。鉴于研究表明肝脏X受体α(LXRA)在胆固醇代谢中起作用，我们分析了LXRA的表达。实时聚合酶链式反应分析表明，喂食果糖的母鼠的后代在其肝脏组织中的Lxragene表达减少。Lxra的表达与DNA甲基化水平和miR-206表达之间存在明确的相关性。焦磷酸测序分析表明，Lxra启动子区域的DNA甲基化水平没有差异，而miR-206在PD 60和160时在肝脏中的表达增加。我们的数据表明，早期母亲接触果糖会导致肝脏miR-206表达水平的变化，从而抑制Lxra的表达。这种现象可能与子代血清高密度脂蛋白胆固醇水平降低有关。
Maternal fructose consumption affects the metabolic functions of offspring later in life. However, the molecular mechanism remains poorly understood. Differences of microRNA expression profile and DNA methylation status are a candidate mechanism to explain the developmental programming that contributes to the development of a metabolic disorder. This study examined the transgenerational effect of maternal fructose consumption from the perspective of epigenetic modification. To do this, we collected serum and liver tissues from male offspring rats that were exposed to maternal distilled water or 20% fructose water during gestation and lactation. A decreased serum high-density lipoprotein cholesterol (HDL-C) level was observed in the offspring of fructose-fed dams at postnatal day (PD) 160. Given research indicating a role of liver X receptor alpha (LXRA) in cholesterol metabolism, we analyzedLxraexpression. Real-time polymerase chain reaction analysis demonstrated that offspring that were delivered from fructose-fed dams exhibited decreasedLxragene expression in their liver tissue. There is a well-established association betweenLxraexpression and the level of DNA methylation and miR-206 expression. Pyrosequencing assays revealed no differences in the level of DNA methylation in theLxrapromoter region, whereas miR-206 expression was increased in the liver at PD 60 and 160. Our data indicate that early-life exposure to maternal fructose results in changing of miR-206 expression level in the liver that suppresses the expression ofLxra. This phenomenon may be associated with the decreased serum HDL-C level in offspring.