Journal Article

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

Ruiz-Rodríguez, Alejandro, Reglero, Guillermo, Soler-Rivas, Cristina, Martin-Hernandez, Roberto, Largo, Carlota, Marín, Francisco R., Caz, Víctor, Gil-Ramírez, Alicia, Rodríguez-Casado, Arantxa, Tabernero, María

2016

Overview

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.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Agaricus - chemistry / Agaricus bisporus / Animals / beta-glucans / beta-Glucans - pharmacology / blood lipids / Caco-2 Cells / Chemistry / Chemistry and Materials Science / Cholesterol, Dietary - administration & dosage / Cholesterol, HDL - blood / Cholesterol, LDL - blood / Diacylglycerol O-Acyltransferase - genetics / Diacylglycerol O-Acyltransferase - metabolism / diet / Diet, High-Fat / Down-Regulation / drugs / ergosterol / Ergosterol - pharmacology / Ezetimibe - pharmacology / fatty liver / feces / Feces - chemistry / functional foods / fungi / gene expression / gene expression regulation / Gene Expression Regulation - drug effects / genes / Hep G2 Cells / high density lipoprotein / human cell lines / Humans / in vitro digestion / ingredients / jejunum / liver / Liver - metabolism / Male / messenger RNA / Mice / Mice, Inbred C57BL / micelles / Nutrition / Original Contribution / Receptors, Cytoplasmic and Nuclear - genetics / Receptors, Cytoplasmic and Nuclear - metabolism / RNA, Messenger - genetics / RNA, Messenger - metabolism / Simvastatin - pharmacology / Sterol Regulatory Element Binding Protein 2 - genetics / Sterol Regulatory Element Binding Protein 2 - metabolism / Sterols - pharmacology / transcription (genetics) / triacylglycerols / Triglycerides - blood / Up-Regulation