Regulation of Cholesterol Homeostasis by the Liver X Receptors in the Central Nervous System
Open accessAbstract
The nuclear oxysterol receptors liver X receptor-α [LXRα (NR1H3)] and LXRβ (NR1H2) coordinately regulate genes involved in cholesterol homeostasis. Although both LXR subtypes are expressed in the brain, their roles in this tissue remain largely unexplored. In this report, we show that LXR agonists have marked effects on gene expression in murine brain tissue both in vitro and in vivo. In primary astrocyte cultures, LXR agonists regulated several established LXR target genes, including ATP binding cassette transporter A1, and enhanced cholesterol efflux. In contrast, little or no effect on gene expression or cholesterol efflux was detected in primary neuronal cultures. Treatment of mice with a selective LXR agonist resulted in the induction of several LXR target genes related to cholesterol homeostasis in the cerebellum and hippocampus. These data provide the first evidence that the LXRs regulate cholesterol homeostasis in the central nervous system. Because dysregulation of cholesterol balance is implicated in central nervous system diseases such as Alzheimer’s and Niemann-Pick disease, pharmacological manipulation of the LXRs may prove beneficial in the treatment of these disorders.
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Innate immune function and brain cholesterol metabolism are both under the control of liver X receptors.
“Both processes happen to be under the control of liver X receptors (LXRs) (Whitney et al., 2002;Zelcer and Tontonoz, 2006).”
From Critical Role of Astroglial Apolipoprotein E and Liver X Receptor-α Expression for Microglial Aβ Phagocytosis (2011) · cites this paper as Whitney et al., 2002
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- Kandel ER, Schwartz JH, Jessell TM 2000 Principles of neural science. New York: McGraw-Hill Professional Publishing
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- Authors
- Whitney, K. D., Watson, M. A., Collins, J. L., Benson, W. G., Stone, T. M., Numerick, M. J., Tippin, T. K., Wilson, J. G., Winegar, D. A., & Kliewer, S. A.
- Affiliations
- GlaxoSmithKline (United States) (US)
- Corresponding author
- Kliewer, Steven A.
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2002-06-01
- Volume
- 16
- Issue
- 6
- Pages
- 1378-1385
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W2116824509
- Cited by
- 211
- References
- 0
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 7 · 2020: 8 · 2019: 7 · 2018: 7 · 2017: 4 · 2016: 7 · 2015: 6 · 2014: 12 · 2013: 15 · 2012: 11
- FWCI
- 9.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- liver X receptor, cholesterol homeostasis, central nervous system, LXR agonists, astrocytes, cholesterol efflux, ABCA1, cerebellum, hippocampus, Alzheimer's disease, Niemann-Pick disease, oxysterol receptors
- MeSH terms
- Animals, Cell Line, Central Nervous System, Cholesterol, Gene Expression Regulation, Homeostasis, Organ Specificity, RNA, Messenger, In Situ Hybridization, Mice
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