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Liver X receptors: new players in atherogenesis?
Virginie Bocher1, Lesley J Millatt, Jean-Charles Fruchart
1UMR 545 INSERM, Department of Atherosclerosis, Lille Pasteur Institute, Lille, France, and Faculty of Pharmacy, University of Lille II, Lille, France.
Purpose Of Review:
The liver X receptors (alpha and beta) are oxysterol-activated nuclear receptors. A large number of liver X receptor target genes with functions in lipid homeostasis have been identified. Increasing evidence indicates that these receptors play a beneficial role in avoiding cholesterol overload by intervening at several steps of cholesterol metabolism. In this review, we describe the most recent developments concerning their functions in cholesterol and lipid metabolism and their impact in atherogenesis.
Recent Findings:
Although potentially undesirable effects of liver X receptor activation on triglyceride metabolism have been observed, recent in-vivo studies confirm that the overall trend is a reduction of atherogenesis.
Summary:
Consequently, liver X receptors are becoming therapeutic targets of great interest for the treatment of atherosclerosis, especially if their action on triglyceride and cholesterol metabolism can be dissociated and isoform-specific ligands identified.
Insights
Liver X receptors (LXRs) are key regulators of cholesterol and lipid metabolism. LXR activation shows promise in reducing atherosclerosis, with ongoing research focusing on isoform-specific therapies.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Metabolic Diseases
Background:
- Liver X receptors (LXRs) are nuclear receptors activated by oxysterols.
- LXRs regulate numerous genes involved in lipid homeostasis.
- Evidence suggests LXRs play a protective role against cholesterol overload.
Purpose of the Study:
- To review recent developments in LXR function regarding cholesterol and lipid metabolism.
- To examine the impact of LXRs on atherogenesis.
- To highlight LXRs as potential therapeutic targets for atherosclerosis.
Main Methods:
- Review of recent in-vivo studies.
- Analysis of gene expression related to lipid metabolism.
- Evaluation of LXR's role in cholesterol regulation.
Main Results:
- LXR activation generally reduces atherogenesis, despite potential effects on triglyceride metabolism.
- In-vivo studies confirm the anti-atherogenic trend of LXR activation.
Conclusions:
- LXRs are promising therapeutic targets for atherosclerosis treatment.
- Future research should focus on dissociating LXR effects on triglyceride and cholesterol metabolism.
- Identification of isoform-specific LXR ligands is crucial for targeted therapies.