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Liver X receptors in lipid signalling and membrane homeostasis
Open accessAbstract
Liver X receptors α and β (LXRα and LXRβ) are nuclear receptors with pivotal roles in the transcriptional control of lipid metabolism. Transcriptional activity of LXRs is induced in response to elevated cellular levels of cholesterol. LXRs bind to and regulate the expression of genes that encode proteins involved in cholesterol absorption, transport, efflux, excretion and conversion to bile acids. The coordinated, tissue-specific actions of the LXR pathway maintain systemic cholesterol homeostasis and regulate immune and inflammatory responses. LXRs also regulate fatty acid metabolism by controlling the lipogenic transcription factor sterol regulatory element-binding protein 1c and regulate genes that encode proteins involved in fatty acid elongation and desaturation. LXRs exert important effects on the metabolism of phospholipids, which, along with cholesterol, are major constituents of cellular membranes. LXR activation preferentially drives the incorporation of polyunsaturated fatty acids into phospholipids by inducing transcription of the remodelling enzyme lysophosphatidylcholine acyltransferase 3. The ability of the LXR pathway to couple cellular sterol levels with the saturation of fatty acids in membrane phospholipids has implications for several physiological processes, including lipoprotein production, dietary lipid absorption and intestinal stem cell proliferation. Understanding how LXRs regulate membrane composition and function might provide new therapeutic insight into diseases associated with dysregulated lipid metabolism, including atherosclerosis, diabetes mellitus and cancer.
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“Liver X receptor transcription factors are key regulators of cholesterol metabolism (29, 30).”
From Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake (2023) · cites this paper as [29]
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“Following systemic adsorption, some secondary BAs in turn impact host physiology though interaction with a variety of host nuclear receptors including FXR, liver X receptor (LXR), pregnane X receptor (PXR), and specific G-protein coupled receptors like TGR5 (Figure 1)40–44.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [41]
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Metadata
- Authors
- Wang, B., & Tontonoz, P.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Tontonoz, Peter
- Venue
- Nature Reviews Endocrinology
- Published
- 2018-06-14
- Volume
- 14
- Issue
- 8
- Pages
- 452-463
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- PMC
- PMC6433546
- OpenAlex
- W2808548053
- Cited by
- 722
- References
- 150
- Citations by year
- 2026: 89 · 2025: 111 · 2024: 110 · 2023: 117 · 2022: 81 · 2021: 94 · 2020: 64 · 2019: 48 · 2018: 8
- FWCI
- 11.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK114373)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- liver X receptor, liver X receptor alpha, LXRβ, nuclear receptors, cholesterol homeostasis, lipid metabolism, SREBP-1c, fatty acid metabolism, membrane homeostasis, polyunsaturated fatty acids, bile acid synthesis, lipoprotein production, intestinal stem cell proliferation, atherosclerosis, diabetes mellitus, cancer
- MeSH terms
- Liver X Receptors, Animals, Cholesterol, Gene Expression Regulation, Homeostasis, Humans, Signal Transduction, Needs Assessment, Lipid Metabolism, Translational Research, Biomedical
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