Oxysterols: From cholesterol metabolites to key mediators.
Oxysterols are cholesterol metabolites that can be produced through enzymatic or radical processes. They constitute a large family of lipids (i.e. the oxysterome) involved in a plethora of physiological processes. They can act through GPCR (e.g. EBI2, SMO, CXCR2), nuclear receptors (LXR, ROR, ERα) and through transporters or regulatory proteins. Their physiological effects encompass cholesterol, lipid and glucose homeostasis. Additionally, they were shown to be involved in other processes such as immune regulatory functions and brain homeostasis. First studied as precursors of bile acids, they quickly emerged as interesting lipid mediators. Their levels are greatly altered in several pathologies and some oxysterols (e.g. 4β-hydroxycholesterol or 7α-hydroxycholestenone) are used as biomarkers of specific pathologies. In this review, we discuss the complex metabolism and molecular targets (including binding properties) of these bioactive lipids in human and mice. We also discuss the genetic mouse models currently available to interrogate their effects in pathophysiological settings. We also summarize the levels of oxysterols reported in two key organs in oxysterol metabolism (liver and brain), plasma and cerebrospinal fluid. Finally, we consider future opportunities and directions in the oxysterol field in order to gain a better insight and understanding of the complex oxysterol system.
Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Belgium.
Valentin
V
Mutemberezi
Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Belgium.
Owein
O
Guillemot-Legris
Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Belgium. Electronic address: giulio.muccioli@uclouvain.be.
Giulio G
GG
Muccioli
D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D023421:Models, Animal; D010088:Oxidoreductases / Q000378:metabolism; D000072376:Oxysterols / Q000737:chemistry / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D014166:Transferases / Q000378:metabolism
D000072376:Oxysterols; D018160:Receptors, Cytoplasmic and Nuclear; D043562:Receptors, G-Protein-Coupled; D002784:Cholesterol; D010088:Oxidoreductases; D014166:Transferases; D006867:Hydrolases
Bioactive lipids; Cytochrome; Hydroxycholesterol; INSIG; Oxysterome; Squalene epoxidase