title: Modulation of cholesterol-related gene expression by ergosterol and ergosterol-enriched extracts obtained from Agaricus bisporus.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Alicia
authors.initials: A
authors.lastname: Gil-Ramírez
authors.affiliation: Department of Experimental Surgery, Research Institute Hospital La Paz (IdiPAZ), Paseo de la Castellana 261, 28046, Madrid, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Caz
authors.affiliation: IMDEA Food Institute, Pabellón Central del Antiguo Hospital de Cantoblanco (Edificio no 7), Crta. de Cantoblanco no 8, 28049, Madrid, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Martin-Hernandez
authors.affiliation: 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.
authors.forename: Francisco R
authors.initials: FR
authors.lastname: Marín
authors.affiliation: Department of Experimental Surgery, Research Institute Hospital La Paz (IdiPAZ), Paseo de la Castellana 261, 28046, Madrid, Spain.
authors.forename: Carlota
authors.initials: C
authors.lastname: Largo
authors.affiliation: IMDEA Food Institute, Pabellón Central del Antiguo Hospital de Cantoblanco (Edificio no 7), Crta. de Cantoblanco no 8, 28049, Madrid, Spain.
authors.forename: Arantxa
authors.initials: A
authors.lastname: Rodríguez-Casado
authors.affiliation: Department of Experimental Surgery, Research Institute Hospital La Paz (IdiPAZ), Paseo de la Castellana 261, 28046, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Tabernero
authors.affiliation: 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.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Ruiz-Rodríguez
authors.affiliation: 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.|IMDEA Food Institute, Pabellón Central del Antiguo Hospital de Cantoblanco (Edificio no 7), Crta. de Cantoblanco no 8, 28049, Madrid, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Reglero
authors.affiliation: 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. cristina.soler@uam.es.
authors.forename: Cristina
authors.initials: C
authors.lastname: Soler-Rivas
mesh_terms: D000364:Agaricus / Q000737:chemistry*; D000818:Animals; D018938:Caco-2 Cells; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D015536:Down-Regulation; D004875:Ergosterol / Q000494:pharmacology*; D000069438:Ezetimibe / Q000494:pharmacology; D005243:Feces / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D013261:Sterols / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation; D047071:beta-Glucans / Q000494:pharmacology; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D051048:Diacylglycerol O-Acyltransferase; D004875:Ergosterol; D000069438:Ezetimibe; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D019821:Simvastatin; D051782:Sterol Regulatory Element Binding Protein 2; D013261:Sterols; D014280:Triglycerides; D047071:beta-Glucans; D000099150:Receptor, Farnesoid X-Activated; C497390:SREBF2 protein, human; C497391:Srebf2 protein, mouse; C494882:Dgat1 protein, mouse
keywords: Cholesterol; Ergosterol; Gene expression; Low-density array (LDA); Supercritical CO2 extraction; White button mushroom