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Modulation of cholesterol-related gene expression by ergosterol and ergosterol-enriched extracts obtained from Agaricus bisporus

机译:双孢蘑菇中麦角固醇和富含麦角固醇的提取物对胆固醇相关基因表达的调节

摘要

[Purpose]: To investigate the effect of two extracts obtained from Agaricus bisporus on the mRNA expression of cholesterol-related genes. One of the extracts contained ergosterol and other fungal sterols (SFE) and the other contained β-glucans and fungal sterols (EβG). [Methods]: Firstly, the dietary mixed micelles (DMMs) generated after in vitro digestion of standards and SFE were applied to Caco2 cells. Then, the lower compartment after a Caco2-transport experiment was applied to HepG2 cells. The mRNA expression was assessed in both cell lines by low-density arrays (LDA). Mice received the extracts, ergosterol or control drugs after 4 weeks of a high-cholesterol diet. The lipid profile of plasma, liver and feces was determined. LDA assays were performed in liver and intestines. [Results]: The DMM fraction of SFE up-regulated the LDLR mRNA expression in Caco2 cells. The lower compartment after Caco2-transport experiments up-regulated LDLR and modulated several other lipid-related genes in HepG2 cells. In mice, SFE decreased TC/HDL ratio and reduced hepatic triglycerides paralleled with down-regulation of Dgat1 expression, while EβG did it without transcriptional changes. Addition of SFE or ergosterol induced in jejunum a similar transcriptional response to simvastatin and ezetimibe; they all down-regulated Srebf2 and Nr1h4 (FXR) genes. [Conclusion]: Ergosterol-containing extracts from A. bisporus lowered hepatic triglyceride and modify the mRNA expression of cholesterol-related genes although the transcriptional regulation was unrelated to changes in plasma lipid profile. These extracts may be useful limiting hepatic steatosis and as bioactive ingredients to design novel functional foods preventing lifestyle-related diseases such as non-alcoholic fatty liver disease.
机译:[目的]研究双孢蘑菇的两种提取物对胆固醇相关基因mRNA表达的影响。其中一种提取物包含麦角固醇和其他真菌固醇(SFE),另一种包含β-葡聚糖和真菌固醇(EβG)。 [方法]:首先,将标准品和SFE体外消化后产生的膳食混合胶束(DMM)应用于Caco2细胞。然后,将Caco2转运实验后的下隔室应用于HepG2细胞。通过低密度阵列(LDA)评估两种细胞系中的mRNA表达。高胆固醇饮食4周后,小鼠接受了提取物,麦角固醇或对照药物。测定血浆,肝和粪便的脂质分布。在肝和肠中进行LDA测定。 [结果]:SFE的DMM组分上调了Caco2细胞中LDLR mRNA的表达。 Caco2转运后的下隔室实验上调了LDLR并调节了HepG2细胞中其他几个与脂质相关的基因。在小鼠中,SFE降低了TC / HDL比率,降低了肝甘油三酸酯,同时下调了Dgat1表达,而EβG却没有转录变化。在空肠中加入SFE或麦角固醇对辛伐他汀和依泽替米贝的转录反应相似;他们都下调了Srebf2和Nr1h4(FXR)基因。 [结论]双孢曲霉含麦角固醇的提取物可降低肝甘油三酯并修饰胆固醇相关基因的mRNA表达,尽管其转录调控与血浆脂质谱的改变无关。这些提取物可用于限制肝脂肪变性,并作为生物活性成分来设计新颖的功能食品,以预防与生活方式有关的疾病,例如非酒精性脂肪肝。

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