ArticleProceedings of the National Academy of Sciences of the United States of America2001
LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 223 papers.
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Who cites it
223 citing papers in PubMed, 661 citations in OpenAlex.
- Identification of Differentially Expressed Proteins in the Serum of Colorectal Cancer Patients Using 2D-DIGE Proteomics Analysis.Pathology oncology research : POR · 2016Trial
- Discovery and implementation of transcriptional biomarkers of synthetic LXR agonists in peripheral blood cells.Journal of translational medicine · 2008Trial
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- TOMM40 suppression promotes neuronal cholesterol imbalance and molecular and behavioral phenotypes of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Deciphering the role of APOE in cerebral amyloid angiopathy: from genetic insights to therapeutic horizons.Annals of medicine · 2025Review
- Myeloid metabolism and its role in immunotherapy of cancer.Journal for immunotherapy of cancer · 2025Review
- Fenchone attenuates CD68-dependent 7-ketocholesterol accumulation, cholesterol dyshomeostasis and inflammatory responses via modulation of macrophage polarization.Inflammopharmacology · 2025Article
- Impaired ApoB secretion triggers enhanced secretion of ApoE to maintain triglyceride homeostasis in hepatoma cells.Journal of lipid research · 2025Article
- Exploring the Roles of Liver X Receptors in Lipid Metabolism and Immunity in Atherosclerosis.Biomolecules · 2025Review
- Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- The Liver X Receptor Promotes Immune Homeostasis via Controlled Activation of the Innate Immune System in the Liver.Biomolecules · 2024Review
- Insights into the roles of Apolipoprotein E in adipocyte biology and obesity.International journal of obesity (2005) · 2024Review
- Multifaceted roles of APOE in Alzheimer disease.Nature reviews. Neurology · 2024Review
- Future therapeutic perspectives in nonalcoholic fatty liver disease: a focus on nuclear receptors, a promising therapeutic target.Medicine and pharmacy reports · 2024Review
- Amelioration of Tau and ApoE4-linked glial lipid accumulation and neurodegeneration with an LXR agonist.Neuron · 2024Article
- Upstream lipid and metabolic systems are potential causes of Alzheimer's disease, Parkinson's disease and dementias.The FEBS journal · 2024Review
- Review
- Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- A proteomics analysis of 5xFAD mouse brain regions reveals the lysosome-associated protein Arl8b as a candidate biomarker for Alzheimer's disease.Genome medicine · 2023Article
163 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apolipoprotein E (apoE) secreted by macrophages in the artery wall exerts an important protective effect against the development of atherosclerosis, presumably through its ability to promote lipid efflux. Previous studies have shown that increases in cellular free cholesterol levels stimulate apoE transcription in macrophages and adipocytes; however, the molecular basis for this regulation is unknown. Recently, Taylor and colleagues [Shih, S. J., Allan, C., Grehan, S., Tse, E., Moran, C. & Taylor, J. M. (2000) J. Biol. Chem. 275, 31567-31572] identified two enhancers from the human apoE gene, termed multienhancer 1 (ME.1) and multienhancer 2 (ME.2), that direct macrophage- and adipose-specific expression in transgenic mice. We demonstrate here that the nuclear receptors LXRalpha and LXRbeta and their oxysterol ligands are key regulators of apoE expression in both macrophages and adipose tissue. We show that LXR/RXR heterodimers regulate apoE transcription directly, through interaction with a conserved LXR response element present in both ME.1 and ME.2. Moreover, we demonstrate that the ability of oxysterols and synthetic ligands to regulate apoE expression in adipose tissue and peritoneal macrophages is reduced in Lxralpha-/- or Lxrbeta-/- mice and abolished in double knockouts. Basal expression of apoE is not compromised in Lxr null mice, however, indicating that LXRs mediate lipid-inducible rather than tissue-specific expression of this gene. Together with our previous work, these findings support a central role for LXR signaling pathways in the control of macrophage cholesterol efflux through the coordinate regulation of apoE, ABCA1, and ABCG1 expression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.