Liver X receptors (LXR) as therapeutic targets in dyslipidemia
Open accessAbstract
Liver X receptors (LXR) α and β belong to a family of nuclear receptors which form heterodimers with the retinoid X receptor (RXR) and, upon ligand binding, stimulate the expression of target genes. LXR were initially described as orphan receptors and later oxidized cholesterol derivatives (oxysterols) were identified as their natural ligands. In addition, several synthetic LXR agonists such as T0901317 and GW3965 were synthesized. Oxysterols are formed in amounts proportional to cholesterol content in the cell and therefore LXR operate as cholesterol sensors which protect from cholesterol overload by inhibiting intestinal cholesterol absorption, stimulating cholesterol efflux from cells to high‐density lipoproteins (HDL), its transport to the liver, conversion to bile acids, and biliary excretion. In addition, LXR agonists activate fatty acid synthesis by stimulating the expression of a lipogenic transcription factor, sterol regulatory element‐binding protein‐1c (SREBP‐1c), leading to the elevation of plasma triglycerides and liver steatosis. Lipogenic effect seems is the most important negative feature of LXR agonists considered as potential hypolidemic drugs. Some of currently used drugs also affect LXR signaling. For example, statins may impair LXR signaling by inhibiting oxysterol synthesis, whereas fibrates and thiazolidinediones increase LXR expression and activity.
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LXR panmodulators are linked to side effects such as hyperlipidemia and liver steatosis.
“Whilst LXR activation seems to have the potential to ameliorate liver fibrosis and despite promising results in animal studies, LXR panmodulators were linked to side effects such as hyperlipidemia and liver steatosis.”
From Nuclear receptors in liver fibrosis (2021) · cites this paper as [164]
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Research works printed but not linked: 1
- Wang MD, Kiss RS, Franklin V, McBride HM, Whitman SC, Marcel YL. Different intracellular trafficking of LDL- and acetylated LDL-derived cholesterol lead to distinct reverse cholesterol transport mechanisms. J Lipid Res 2007;48:633-645.
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HDL-targeted therapies: progress, failures and future
Kingwell, B. A., Chapman, M. J., Kontush, A., & Miller, N. E. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4279 · Cited by 354 · see citing works
Nuclear receptors in liver fibrosis
Königshofer, P., Brusilovskaya, K., Petrenko, O., Hofer, B. S., Schwabl, P., Trauner, M., & Reiberger, T. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166235 · Cited by 45 · see citing works
- Authors
- Bełtowski, J.
- Affiliations
- Medical University of Lublin (PL)
- Corresponding author
- Bełtowski, Jerzy
- ORCID
- Bełtowski, Jerzy
- Venue
- Cardiovascular Therapeutics
- Publisher
- Wiley
- Published
- 2008-11-11
- Volume
- 26
- Issue
- 4
- Pages
- 297-316
- ISSN
- 1755-5914 (ISSN-L)
- 1755-5922
- OpenAlex
- W2034339368
- Cited by
- 132
- References
- 141
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 6 · 2022: 3 · 2021: 8 · 2020: 8 · 2019: 11 · 2018: 11 · 2017: 10 · 2016: 9 · 2015: 6 · 2014: 6 · 2013: 16 · 2012: 9
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cardiovascular Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- liver X receptor, LXR agonists, dyslipidemia, oxysterols, cholesterol sensing, intestinal cholesterol absorption, cholesterol efflux, bile acid synthesis, SREBP-1c, fatty acid synthesis, hepatic steatosis, triglycerides, statins, fibrates, thiazolidinediones, lipid-lowering drugs, retinoid X receptor, nuclear receptors
- MeSH terms
- Liver X Receptors, Benzenesulfonamides, Animals, Benzoates, Benzylamines, Cholesterol, DNA-Binding Proteins, Fluorocarbons, Hydrocarbons, Fluorinated, Sulfonamides, Receptors, Cytoplasmic and Nuclear, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Dyslipidemias, Orphan Nuclear Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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