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Accumulation of foam cells in liver X receptor-deficient mice
Gertrud U Schuster1, Paolo Parini, Ling Wang
1Department of Biosciences at Novum, Karolinska Institutet, Huddinge, Sweden. gertrud.schuster@csb.ki.se
Background:
The nature of some of the target genes for liver X receptors (LXRs)-alpha and -beta, such as sterol regulatory element binding protein-1 and ATP-binding cassette transporter proteins, suggests a pivotal role of these nuclear receptors in the regulation of fatty acid and cholesterol homeostasis. The present study aimed to elucidate the physiological relevance of both LXRs with regard to lipid metabolism and macrophage cholesterol efflux.
Methods And Results:
Mice depleted for LXRalpha, LXRbeta, or both were fed low-fat rodent chow for 18 months before investigations. The combined deficiency of LXRalpha and LXRbeta was linked to impaired triglyceride metabolism, increased LDL and reduced HDL cholesterol levels, and cholesterol accumulation in macrophages (foam cells) of the spleen, lung, and arterial wall.
Conclusions:
Our data demonstrate the physiological importance of both LXRs in lipid metabolism and strongly indicate that both LXRs have a protective role against the development of atherosclerosis.
Insights
Liver X Receptors (LXRs) are crucial for maintaining lipid balance. Combined LXRalpha and LXRbeta deficiency in mice impaired triglyceride metabolism and promoted cholesterol buildup, indicating their protective role against atherosclerosis.
Area of Science:
- Molecular biology
- Endocrinology
- Cardiovascular research
Background:
- Liver X Receptors (LXRs) alpha and beta are nuclear receptors involved in lipid homeostasis.
- Target genes include sterol regulatory element binding protein-1 and ATP-binding cassette transporters.
- LXRs play a key role in regulating fatty acid and cholesterol metabolism.
Purpose of the Study:
- To investigate the physiological role of LXRalpha and LXRbeta in lipid metabolism.
- To determine the impact of LXR deficiency on macrophage cholesterol efflux.
- To elucidate the relevance of LXRs in the context of atherosclerosis development.
Main Methods:
- Mice models with genetic deficiencies in LXRalpha, LXRbeta, or both were utilized.
- Animals were maintained on a low-fat diet for 18 months.
- Metabolic parameters and cholesterol accumulation were assessed.
Main Results:
- Combined LXRalpha and LXRbeta deficiency led to impaired triglyceride metabolism.
- Deficiency resulted in elevated LDL and reduced HDL cholesterol levels.
- Significant cholesterol accumulation was observed in macrophages within the spleen, lung, and arterial wall.
Conclusions:
- Both LXRalpha and LXRbeta are physiologically important for maintaining lipid metabolism.
- LXRs play a critical protective role in preventing the development of atherosclerosis.
- These findings highlight LXRs as potential therapeutic targets for cardiovascular disease.
