Hepatic Peroxisomal Fatty Acid β-Oxidation Is Regulated by Liver X Receptor α
| Autor: | Guoqing Cao, Patrick I. Eacho, Shuyu Li, James Ficorilli, Michael E. Christe, Angela M. Siesky, Hong Gao, Tonghuan Hu, Laura F. Michael, M. Dodson Michael, Timothy P. Ryan, Patricia S. Foxworthy |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Hydrocarbons Fluorinated Receptors Cytoplasmic and Nuclear Mitochondrion Biology Ligands Mice Endocrinology Internal medicine Peroxisomes medicine Animals PPAR alpha Receptor Liver X receptor Enoyl-CoA Hydratase Beta oxidation Liver X Receptors Mice Knockout chemistry.chemical_classification Sulfonamides Dose-Response Relationship Drug Thiolase Fatty Acids Fatty acid Peroxisome Acetyl-CoA C-Acyltransferase Orphan Nuclear Receptors DNA-Binding Proteins Mice Inbred C57BL Gene Expression Regulation Liver chemistry Biochemistry Free fatty acid receptor lipids (amino acids peptides and proteins) Acyl Coenzyme A Oxidation-Reduction |
| Zdroj: | Endocrinology. 146:5380-5387 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2005-0591 |
| Popis: | Peroxisomes are the exclusive site for the beta-oxidation of very-long-chain fatty acids of more than 20 carbons in length (VLCFAs). Although the bulk of dietary long-chain fatty acids are oxidized in the mitochondria, VLCFAs cannot be catabolized in mitochondria and must be shortened first by peroxisomal beta-oxidation. The regulation of peroxisomal, mitochondrial, and microsomal fatty acid oxidation systems in liver is mediated principally by peroxisome proliferator-activated receptor alpha (PPARalpha). In this study we provide evidence that the liver X receptor (LXR) regulates the expression of the genetic program for peroxisomal beta-oxidation in liver. The genes encoding the three enzymes of the classic peroxisomal beta-oxidation cycle, acyl-coenzyme A (acyl-CoA) oxidase, enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase, are activated by the LXR ligand, T0901317. Accordingly, administration of T0901317 in mice promoted a dose-dependent and greater than 2-fold increase in the rate of peroxisomal beta-oxidation in the liver. The LXR effect is independent of PPARalpha, because T0901317-induced peroxisomal beta-oxidation in the liver of PPARalpha-null mice. Interestingly, T0901317-induced peroxisomal beta-oxidation is dependent on the LXRalpha isoform, but not the LXRbeta isoform. We propose that induction of peroxisomal beta-oxidation by LXR agonists may serve as a counterregulatory mechanism for responding to the hypertriglyceridemia and liver steatosis that is promoted by potent LXR agonists in vivo; however, additional studies are warranted. |
| Databáze: | OpenAIRE |
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