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

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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.

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Abbreviations

CH+ERG-lard:

Lard enriched with cholesterol and ergosterol

CH-Lard:

Lard enriched with cholesterol

CH+SFE-lard:

Lard enriched with cholesterol and the SFE extract

DMM:

Dietary mixed micelles

EβG extract:

Extract containing ergosterol and β-glucans

FXR:

Farnesoid X receptor

HDL:

High-density lipoprotein

LDA:

Low-density array

LDL:

Low-density lipoprotein

LXR:

Liver X receptor

SFE extract:

Extract obtained by supercritical fluid extraction

SREBP:

Sterol regulatory element-binding protein

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Acknowledgments

The research was supported by AGL2010-21537 national R+D program from the Spanish Ministry of Science and Innovation and ALIBIRD-C M S2009/AGR-1469 regional program from the Community of Madrid (Spain). CTICH (Centro Tecnológico de Investigación del Champiñón de La Rioja, Autol, Spain) is also acknowledged for the cultivation and supplying of the mushrooms fruiting bodies and Maria Navarro-Rubio for her technical assistance.

Conflict of interest

None.

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    Authors and Affiliations

    1. 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

      Alicia Gil-Ramírez, Francisco R. Marín, Alejandro Ruiz-Rodríguez, Guillermo Reglero & Cristina Soler-Rivas

    2. Department of Experimental Surgery, Research Institute Hospital La Paz (IdiPAZ), Paseo de la Castellana 261, 28046, Madrid, Spain

      Víctor Caz, Carlota Largo & María Tabernero

    3. IMDEA Food Institute, Pabellón Central del Antiguo Hospital de Cantoblanco (Edificio no 7), Crta. de Cantoblanco no 8, 28049, Madrid, Spain

      Roberto Martin-Hernandez, Arantxa Rodríguez-Casado & Guillermo Reglero

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    1. Alicia Gil-Ramírez
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    Correspondence to Cristina Soler-Rivas.

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    Alicia Gil-Ramírez and Víctor Caz have equally contributed.

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    Gil-Ramírez, A., Caz, V., Martin-Hernandez, R. et al. Modulation of cholesterol-related gene expression by ergosterol and ergosterol-enriched extracts obtained from Agaricus bisporus . Eur J Nutr 55, 1041–1057 (2016). https://doi.org/10.1007/s00394-015-0918-x

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