ArticleThe Journal of clinical investigation2015
Hepatic TRAP80 selectively regulates lipogenic activity of liver X receptor.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- GCN5 drives MASLD progression through LXRα/SREBP1c signaling pathway-mediated de novo lipogenesis.Nature communications · 2026Article
- Integrative analysis of genome and transcriptome reveals a novel regulator for pork intramuscular fat content.Genetics, selection, evolution : GSE · 2025Article
- In search of nonlipogenic ABCA1 inducers (NLAI): precision coregulator TR-FRET identifies diverse signatures for LXR ligands.bioRxiv : the preprint server for biology · 2025Article
- Targeting macrophages in atherosclerosis using nanocarriers loaded with liver X receptor agonists: A narrow review.Frontiers in molecular biosciences · 2023Review
- Redox-Unlockable Nanoparticle-Based MST1 Delivery System to Attenuate Hepatic Steatosis via the AMPK/SREBP-1c Signaling Axis.ACS applied materials & interfaces · 2022Article
- Regulation of Hepatic Gluconeogenesis by Nuclear Receptor Coactivator 6.Molecules and cells · 2022Article
- The cell polarity kinase Par1b/MARK2 activation selects specific NF-kB transcripts via phosphorylation of core mediator Med17/TRAP80.Molecular biology of the cell · 2021Article
- Thyroid Hormones and Functional Ovarian Reserve: Systemic vs. Peripheral Dysfunctions.Journal of clinical medicine · 2020Review
- Dietary Sargassum fusiforme improves memory and reduces amyloid plaque load in an Alzheimer's disease mouse model.Scientific reports · 2019Article
- Inhibition of protein arginine methyltransferase 3 activity selectively impairs liver X receptor-driven transcription of hepatic lipogenic genes in vivo.British journal of pharmacology · 2018Article
- The challenges and promise of targeting the Liver X Receptors for treatment of inflammatory disease.Pharmacology & therapeutics · 2018Review
- (-)-Epigallocatechin-3-Gallate Ameliorates Atherosclerosis and Modulates Hepatic Lipid Metabolic Gene Expression in Apolipoprotein E Knockout Mice: Involvement of TTC39B.Frontiers in pharmacology · 2018Article
- SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology.Nature reviews. Endocrinology · 2017Review
- Lipid droplet-associated proteins in atherosclerosis (Review).Molecular medicine reports · 2016Review
- Stable liver-specific expression of human IDOL in humanized mice raises plasma cholesterol.Cardiovascular research · 2016Article
- Caveolae and Caveolin-1 Integrate Reverse Cholesterol Transport and Inflammation in Atherosclerosis.International journal of molecular sciences · 2016Review
- Regulation of metabolism by the Mediator complex.Biophysics reports · 2016Article
- Liver X receptors at the intersection of lipid metabolism and atherogenesis.Atherosclerosis · 2015Review
- Muscle as a "mediator" of systemic metabolism.Cell metabolism · 2015Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammation in response to excess low-density lipoproteins in the blood is an important driver of atherosclerosis development. Due to its ability to enhance ATP-binding cassette A1-dependent (ABCA1-dependent) reverse cholesterol transport (RCT), liver X receptor (LXR) is an attractive target for the treatment of atherosclerosis. However, LXR also upregulates the expression of sterol regulatory element-binding protein 1c (SREBP-1c), leading to increased hepatic triglyceride synthesis, an independent risk factor for atherosclerosis. Here, we developed a strategy to separate the favorable and unfavorable effects of LXR by exploiting the specificity of the coactivator thyroid hormone receptor-associated protein 80 (TRAP80). Using human hepatic cell lines, we determined that TRAP80 selectively promotes the transcription of SREBP-1c but not ABCA1. Adenovirus-mediated expression of shTRAP80 inhibited LXR-dependent SREBP-1c expression and RNA polymerase II recruitment to the LXR responsive element (LXRE) of SREBP-1c, but not to the LXRE of ABCA1. In murine models, liver-specific knockdown of TRAP80 ameliorated liver steatosis and hypertriglyceridemia induced by LXR activation and maintained RCT stimulation by the LXR ligand. Together, these data indicate that TRAP80 is a selective regulator of hepatic lipogenesis and is required for LXR-dependent SREBP-1c activation. Moreover, targeting the interaction between TRAP80 and LXR should facilitate the development of potential LXR agonists that effectively prevent atherosclerosis.
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Registered trials
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 Socratic graph.