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Maternal fructose consumption down-regulates Lxra expression via miR-206-mediated regulation.
The Journal of Nutritional Biochemistry ( IF 5.6 ) Pub Date : 2020-04-14 , DOI: 10.1016/j.jnutbio.2020.108386
Mirai Yamazaki 1 , Eiji Munetsuna 2 , Hiroya Yamada 3 , Yoshitaka Ando 4 , Genki Mizuno 5 , Ryosuke Fujii 6 , Yuki Nouchi 4 , Itsuki Kageyama 4 , Atsushi Teshigawara 4 , Hiroaki Ishikawa 4 , Koji Suzuki 6 , Yohei Shimono 2 , Shuji Hashimoto 3 , Koji Ohashi 4
Affiliation  

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 analyzed Lxra expression. Real-time polymerase chain reaction analysis demonstrated that offspring that were delivered from fructose-fed dams exhibited decreased Lxra gene expression in their liver tissue. There is a well-established association between Lxra expression and the level of DNA methylation and miR-206 expression. Pyrosequencing assays revealed no differences in the level of DNA methylation in the Lxra promoter 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 of Lxra. This phenomenon may be associated with the decreased serum HDL-C level in offspring.



中文翻译:

孕妇摄入果糖可通过miR-206介导的调控下调Lxra表达。

孕妇摄入果糖会影响后代的后代代谢功能。但是,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有助于代谢性疾病发展的发育程序的候选机制。这项研究从表观遗传修饰的角度研究了母体果糖消耗的代际效应。为此,我们从雄性后代雄性大鼠中收集血清和肝脏组织,这些雌性后代在妊娠和哺乳期间暴露于母体蒸馏水或20%果糖水中。在出生后第160天,在果糖喂养的大坝的后代中观察到血清高密度脂蛋白胆固醇(HDL-C)水平降低。Lxra表达。实时聚合酶链反应分析表明,从果糖喂养的大坝中分娩的后代在肝脏组织中表现出降低的Lxra基因表达。Lxra表达与DNA甲基化水平和miR-206表达之间存在公认的关联。焦磷酸测序分析显示Lxra启动子区域的DNA甲基化水平无差异,而肝脏中PD 60和160处miR-206的表达增加。我们的数据表明,母亲果糖的早期暴露导致miR-的改变。肝脏中的206表达水平可抑制Lxra的表达。这种现象可能与后代血清HDL-C水平降低有关。

更新日期:2020-04-14
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