Author/Editor		Ali, Zeina; Heverin, Maura; Olin, Maria; Ačimovič, Jure
Title		On the regulatory role of side-chain hydroxylated oxysterols in the brain. Lessons from CYP27A1 transgenic and cyp27a1-/- mice
Type		članek
Source		J Lipid Res
Vol. and No.		Letnik 54, št. 4
Publication year		2013
Volume		str. 1033-43
Language		eng
Abstract		The two oxysterols 27-hydroxycholesterol (27OH) and 24S-hydroxycholesterol (24OH) are both inhibitors of cholesterol synthesis and activators of LXR in vitro. Their role as physiological regulators under in vivo conditions is controversial, however. In the present work we utilized a previously described mouse model with overexpressed human CYP27A1. The levels of 27OH were increased about 12-fold in the brain. The brain levels of HMG CoA reductase mRNA and HMG CoA synthase mRNA levels were increased. In accordance with increased cholesterol synthesis most of the cholesterol precursors were also increased. The level of 24OH, the dominating oxysterol in the brain, was decreased by about 25%, most probably due to increased metabolism by CYP27A1. The LXR target genes were unaffected or slightly changed in a direction opposite that expected for an LXR activation. In the brain of cyp27-/- mice cholesterol synthesis was slightly increased with increased levels of cholesterol precursors but normal mRNA levels of HMG CoA reductase and HMG CoA synthase. The mRNA levels corresponding to LXR target genes were not affected. The results are consistent with the possibility that both 24OH and 27OH are physiological suppressors of cholesterol synthesis in the brain. The results do not support the contention that 27OH is a general activator of LXR target genes in this organ.