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The reduced form of coenzyme Q 10 mediates distinct effects on cholesterol metabolism at the transcriptional and metabolite level in SAMP1 mice
Author(s) -
Schmelzer Constance,
Okun Jürgen G.,
Haas Dorothea,
Higuchi Keiichi,
Sawashita Jinko,
Mori Masayuki,
Döring Frank
Publication year - 2010
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.388
Subject(s) - ubiquinol , metabolite , desmosterol , metabolism , cholesterol , biology , medicine , endocrinology , liver x receptor , biochemistry , chemistry , coenzyme q – cytochrome c reductase , sterol , gene , nuclear receptor , transcription factor , mitochondrion , cytochrome c
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. © 2010 IUBMB IUBMB Life, 2010