Oxysterols in human circulation: which role do they have?
Oxysterols are oxygenated derivatives of cholesterol that are intermediates in cholesterol excretion pathways. They may also be regarded as transport forms of cholesterol and introduction of an additional hydroxyl group facilitates flux of cholesterol across cell membranes and the blood-brain barrier. According to current concepts, oxysterols are also mediating a number of cholesterol-induced metabolic effects. The recent discovery of nuclear receptors with an affinity for oxysterols has given support to this concept. Nuclear receptors such as liver X receptor alpha do have a role in cholesterol homeostasis, but there is still only indirect evidence that oxysterols are the physiological ligands. In this overview we report some recent advancements in our knowledge about the origin and metabolic fate of the quantitatively most important oxysterols occurring in the circulation. In addition, we discuss the possibility that some of these oxysterols may activate liver X receptors and regulate cholesterol homeostasis.
Björkhem
Ingemar
I
Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, Sweden. ingemar.bjorkhem@chemlab.hs.sll.se
Meaney
Steve
S
Diczfalusy
Ulf
U
D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D004268:DNA-Binding Proteins; D006888:Hydroxycholesterols / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013261:Sterols / Q000097:blood*
D004268:DNA-Binding Proteins; D006888:Hydroxycholesterols; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D013261:Sterols; D002784:Cholesterol