Liver X receptors as regulators of macrophage inflammatory and metabolic pathways
Open accessAbstract
The liver X receptors (LXRα and LXRβ) are members of the nuclear receptor family of transcription factors that play essential roles in the transcriptional control of lipid metabolism. LXRs are endogenously activated by modified forms of cholesterol known as oxysterols and control the expression of genes important for cholesterol uptake, efflux, transport, and excretion in multiple tissues. In addition to their role as cholesterol sensors, a number of studies have implicated LXRs in the modulation of innate and adaptive immune responses. Both through activation and repression mechanisms, LXRs regulate diverse aspects of inflammatory gene expression in macrophages. The ability of LXRs to coordinate metabolic and immune responses constitutes an attractive therapeutic target for the treatment of chronic inflammatory disorders. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.
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Genetic variants in several targets of LXR/RXR transcription factors have been associated with risk for AD, including APOE, CLU, ABCA1, ABCA7, ABCG1, and TREM2.
“Indeed, genetic variants in several targets of LXR/RXR transcription factors have been associated with risk for AD, e.g. APOE, CLU, ABCA1, ABCA7, ABCG1, TREM2 (A-González and Castrillo, 2011; Pimenova et al., 2017b; Savage et al., 2015).”
From Alzheimer's-associated PU.1 expression levels regulate microglial inflammatory response (2021) · cites this paper as A-González and Castrillo, 2011
Section 4 identifies ABCA1 as a direct LXR target and reports LXR-dependent expression of ABCG1 and ApoE. Section 8 discusses LXR activity in models of Alzheimer’s disease, but the paper does not report Alzheimer’s-risk genetic variants in these genes or establish CLU, ABCA7, and TREM2 as LXR/RXR targets. Pages are not specified in our copy. (LLM, conf=0.88)
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References 202 · Cited by 139
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- Authors
- A-González, N., & Castrillo, A.
- Affiliations
- Universidad de Las Palmas de Gran Canaria (ES)
- Corresponding author
- Castrillo, Antonio
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 1812
- Issue
- 8
- Pages
- 982-994
- ISSN
- 0925-4439 (ISSN-L)
- OpenAlex
- W2021539595
- Cited by
- 139
- References
- 202
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 9 · 2023: 13 · 2022: 12 · 2021: 17 · 2020: 14 · 2019: 17 · 2018: 11 · 2017: 9 · 2016: 5 · 2015: 6 · 2014: 4 · 2013: 6 · 2012: 4
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- Fundación Canaria de Investigación y Salud
- Ministerio de Ciencia e Innovación
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- liver X receptor, liver X receptor alpha, LXRβ, macrophages, inflammation, metabolic pathways, oxysterols, cholesterol metabolism, nuclear receptors, immune regulation, chronic inflammation, transcriptional regulation
- MeSH terms
- Liver X Receptors, Adaptation, Physiological, Animals, Humans, Immunity, Innate, Inflammation, Macrophages, Transcription Factors, Apoptosis, Inflammation Mediators, Orphan Nuclear Receptors
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