Gil-Ramírez Alicia, Caz Víctor, Martin-Hernandez Roberto, Marín Francisco R, Largo Carlota, Rodríguez-Casado Arantxa, Tabernero María, Ruiz-Rodríguez Alejandro, Reglero Guillermo, Soler-Rivas Cristina
Department of Production and Characterization of Novel Foods, CIAL - Research Institute in Food Science (UAM+CSIC), Universidad Autónoma de Madrid, C/Nicolas Cabrera 9, Campus de Cantoblanco, 28049, Madrid, Spain.
Department of Experimental Surgery, Research Institute Hospital La Paz (IdiPAZ), Paseo de la Castellana 261, 28046, Madrid, Spain.
Eur J Nutr. 2016 Apr;55(3):1041-57. doi: 10.1007/s00394-015-0918-x. Epub 2015 May 7.
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).
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.
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.
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.
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。其中一种提取物含有麦角固醇和其他真菌固醇（SFE），另一种含有β-葡聚糖和真菌固醇（EβG）。
首先，将标准品和SFE体外消化后产生的膳食混合微粒（DMMs）应用于Caco2细胞。然后，将Caco2转运实验后的下层隔室应用于HepG2细胞。通过低密度阵列（LDA）评估两种细胞系中的mRNA表达。在高胆固醇饮食4周后，小鼠接受提取物、麦角固醇或对照药物。测定血浆、肝脏和粪便的脂质谱。在肝脏和肠道中进行LDA分析。
SFE的DMM部分上调了Caco2细胞中LDLR mRNA的表达。Caco2转运实验后的下层隔室上调了HepG2细胞中的LDLR并调节了其他几个脂质相关基因。在小鼠中，SFE降低了TC/HDL比值并降低了肝脏甘油三酯，同时Dgat1表达下调，而EβG在无转录变化的情况下做到了这一点。添加SFE或麦角固醇在空肠中诱导出与辛伐他汀和依泽替米贝相似的转录反应；它们都下调了Srebf2和Nr1h4（FXR）基因。
双孢蘑菇中含麦角固醇的提取物降低了肝脏甘油三酯并改变了胆固醇相关基因的mRNA表达，尽管转录调节与血浆脂质谱的变化无关。这些提取物可能有助于限制肝脏脂肪变性，并作为生物活性成分用于设计预防非酒精性脂肪肝病等生活方式相关疾病的新型功能性食品。
