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The LXRs: a new class of oxysterol receptors
D J Peet1, B A Janowski, D J Mangelsdorf
1Howard Hughes Medical Institute, Department of Pharmacology, Universityof Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9050, USA.
Abstract:
The liver X receptors (LXRs) are a family of transcription factors that were first identified as orphan members of the nuclear receptor superfamily. The identification of a specific class of oxidized derivatives of cholesterol as ligands for the LXRs has been crucial to helping understand the function of these receptors in vivo and first suggested their role in the regulation of lipid metabolism. Confirmation of this role has come from the recent analysis of LXR-deficient mice, which has demonstrated the essential function of one of these receptors in the liver as a major sensor of dietary cholesterol.
Insights
Liver X receptors (LXRs) regulate lipid metabolism. Studies in LXR-deficient mice confirm LXRs act as key sensors for dietary cholesterol in the liver.
Area of Science:
- Molecular biology
- Endocrinology
- Metabolism
Background:
- Liver X receptors (LXRs) are nuclear receptors.
- Initially identified as orphan receptors.
- Oxysterols were found to be LXR ligands.
Purpose of the Study:
- To understand the in vivo function of LXRs.
- To elucidate the role of LXRs in lipid metabolism.
- To investigate LXR's role in cholesterol sensing.
Main Methods:
- Ligand identification for LXRs.
- Analysis of LXR-deficient mouse models.
Main Results:
- Identification of oxidized cholesterol derivatives as LXR ligands.
- Demonstration of LXR's crucial role in regulating lipid metabolism.
- Confirmation of LXR's function as a major dietary cholesterol sensor in the liver.
Conclusions:
- LXRs are critical regulators of lipid metabolism.
- LXRs play a vital role in sensing dietary cholesterol.
- Further research into LXR function is warranted.