The reduced form of coenzyme Q 10 mediates distinct effects on cholesterol metabolism at the transcriptional and metabolite level in SAMP1 mice

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