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Gestational hypercholesterolemia alters fetal hepatic lipid metabolism and microRNA expression in Apo-E-deficient mice

机译:妊娠高胆固醇血症在Apo-E缺陷小鼠中改变胎儿肝脂代谢和MicroRNA表达

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摘要

Maternal hypercholesterol-emia (MHC) is a pathological condition characterized by an exaggerated rise in maternal serum cholesterol during gestation, which can alter offspring hepatic lipid metabolism. However, the extent that these maladaptations occur during gestation and the molecular mechanisms involved remain unknown. MicoRNAs (miRNA) are small, noncoding RNAs that contribute to the development and progression of nonalcoholic fatty liver disease. Therefore, we sought to determine the degree to which in utero exposure to excessive cholesterol affects fetal hepatic lipid metabolism and miRNA expression. Twelve female apoE ' mice were randomly assigned to two different chow-based diets throughout gestation: control (CON) or the CON diet with cholesterol (0.15%). MHC reduced maternal fecundity and reduced litter size and weight. On gestational day 18, fetuses from MHC dams possessed increased placenta! cholesterol and hepatic triglycerides (TG), which were accompanied by a downregulation in the expression of hepatic lipogenic and TG synthesis and transport genes. Furthermore, fetal livers from MHC mothers showed increased miRNA-27a and reduced miRNA-200c expression. In summary, in utero exposure to MHC alters fetal lipid metabolism and lends mechanistic insight that implicates early changes in miRNA expression that may link to later-life programming of disease risk.
机译:母体高胆固醇 - emia(MHC)是一种病理状况,其特征在于妊娠期间母体血清胆固醇的夸张升高,这可以改变后代肝脂代谢。然而,在妊娠期间发生这些治疗的程度和所涉及的分子机制仍然未知。 Micornas(miRNA)是小的,非典型的RNA有助于非酒精性脂肪肝病的发展和进展。因此,我们试图确定子宫暴露于过量胆固醇的程度影响胎儿肝脂代谢和miRNA表达。在妊娠中随机分配12个女Apoe的小鼠:控制(CON)或胆固醇的肠果(0.15%)。 MHC减少产妇繁殖力,减少凋落物尺寸和重量。在妊娠第18天,来自MHC水坝的胎儿具有增加的胎盘!胆固醇和肝甘油三酯(Tg),其伴随着肝脂肪生成和Tg合成和运输基因表达的下调。此外,来自MHC母亲的胎儿肝脏显示MiRNA-27a和MiRNA-200C表达减少。总之,在UTERO暴露于MHC时改变胎儿脂质代谢并提供机械洞察力,这意味着MIRNA表达的早期变化可能链接到疾病风险的后期生命编程。

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