Cited by 729Cholesterol and Lipid MetabolismLipid Membrane Structure and BehaviorCancer, Lipids, and Metabolism

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Liver X receptors in lipid signalling and membrane homeostasis

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Wang, Bo, Tontonoz, Peter·2018·Nature Reviews Endocrinology

DOI 10.1038/s41574-018-0037-xPMC PMC6433546

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Abstract

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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Authors: Wang, B., & Tontonoz, P.
Affiliations: University of California, Los Angeles (US)
Corresponding author: Tontonoz, Peter
ORCID: Wang, Bo
Tontonoz, Peter
Venue: Nature Reviews Endocrinology
Publisher: Springer Science and Business Media LLC
Published: 2018-06-14
Volume: 14
Issue: 8
Pages: 452-463
ISSN: 1759-5029 (ISSN-L)
1759-5037
DOI: 10.1038/s41574-018-0037-x
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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Liver X receptors in lipid signalling and membrane homeostasis

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