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. 2016 Apr;55(3):1041-57.
doi: 10.1007/s00394-015-0918-x. Epub 2015 May 7.

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

Alicia Gil-Ramírez  1 , Víctor Caz  2 , Roberto Martin-Hernandez  3 , Francisco R Marín  1 , Carlota Largo  2 , Arantxa Rodríguez-Casado  3 , María Tabernero  2 , Alejandro Ruiz-Rodríguez  1 , Guillermo Reglero  1   3 , Cristina Soler-Rivas  4
Affiliations

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

Alicia Gil-Ramírez et al. Eur J Nutr. 2016 Apr.

Abstract

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.

Keywords: Cholesterol; Ergosterol; Gene expression; Low-density array (LDA); Supercritical CO2 extraction; White button mushroom.

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