title: The reduced form of coenzyme Q10 mediates distinct effects on cholesterol metabolism at the transcriptional and metabolite level in SAMP1 mice.
abstract: Studies in humans and mice indicate a role for coenzyme Q(10) (CoQ(10)) in gene expression. To analyze this function in relation to metabolism, SAMP1 mice were supplemented with the reduced (ubiquinol) or oxidized (ubiquinone) form of CoQ(10) (500 mg/kg BW/d) for 14 months. Microarray analyses in liver tissues of SAMP1 mice identified 946 genes as differentially expressed between ubiquinol-treated and control animals (≥1.5-fold, P < 0.05). Text mining analyses revealed for a part of the ubiquinol-regulated genes, a functional connection in PPARα and LXR/RXR signalling pathways. Because these pathways are involved in cholesterol homeostasis, relevant metabolites were determined by gas chromatography/mass spectrometry (GC/MS). We found a significant increase of desmosterol (2.0-fold, P < 0.001) in the liver of ubiquinol-supplemented SAMP1 mice when related to control animals. In agreement, cholesterol concentrations were also distinctly increased (1.3-fold, P = 0.057). The Q(10)H(2)-induced PPARα and LXR/RXR gene expression signatures and effects on cholesterol metabolism were not apparent for the oxidized form of CoQ(10). In conclusion, the reduced form of CoQ(10) mediates distinct effects on cholesterol metabolism at the transcriptional and metabolite level in SAMP1 mice.
authors.affiliation: Department of Molecular Prevention, Institute of Human Nutrition and Food Science, Molecular Prevention, Christian-Albrechts-University of Kiel, Kiel, Germany. schmelzer@molprev.uni-kiel.de
authors.forename: Constance
authors.initials: C
authors.lastname: Schmelzer
authors.forename: Jürgen G
authors.initials: JG
authors.lastname: Okun
authors.forename: Dorothea
authors.initials: D
authors.lastname: Haas
authors.forename: Keiichi
authors.initials: K
authors.lastname: Higuchi
authors.forename: Jinko
authors.initials: J
authors.lastname: Sawashita
authors.forename: Masayuki
authors.initials: M
authors.lastname: Mori
authors.forename: Frank
authors.initials: F
authors.lastname: Döring
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D003897:Desmosterol / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D020869:Gene Expression Profiling; D008099:Liver / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000378:metabolism; D047488:Retinoid X Receptors / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D047493:PPAR alpha; D047488:Retinoid X Receptors; D014451:Ubiquinone; D003897:Desmosterol; D002784:Cholesterol; C003741:ubiquinol