Regulation of the angiopoietin-like protein 3 gene by LXR

Q: What does this research mean for the field?

The angiopoietin-like protein 3 (Angptl3) gene is a direct transcriptional target of the liver X receptor (LXR), providing a novel mechanism by which LXR regulates lipid metabolism. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Rebecca Kaplan; Theresa Zhang; Melba Hernandez; Frank Xiaodong Gan; Samuel D. Wright; M. Gerard Waters; Tian‐Quan Cai

doi:10.1194/jlr.m200367-jlr200

January 1, 2003Journal of Lipid ResearchOpen Access

Regulation of the angiopoietin-like protein 3 gene by LXR

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Key Points

To determine whether angiopoietin-like protein 3 (Angptl3) is a direct transcriptional target of liver X receptor (LXR) and elucidate its role in LXR-mediated lipid regulation.
Assessed hepatic Angptl3 mRNA and plasma lipid levels in mice fed a high-cholesterol diet or treated orally with the synthetic LXR agonist T0901317 using quantitative real-time RT-PCR.
Treated human HepG2 hepatoma cells with LXR- and retinoid X receptor (RXR)-selective agonists to evaluate Angptl3 expression changes.
Cloned the human Angptl3 promoter into luciferase reporter vectors and performed site-directed mutagenesis on the predicted LXR response element (DR4 motif) during HepG2 transfection assays.
Mice receiving a high-cholesterol diet or the synthetic LXR agonist T0901317 exhibited significant increases in hepatic Angptl3 mRNA expression and elevated plasma lipids.
Treatment of HepG2 cells with LXR-selective agonists drove a dose-dependent increase in endogenous Angptl3 mRNA and enhanced Angptl3 promoter activity.
Site-directed mutation of the DR4 response element in the Angptl3 promoter completely abolished LXR agonist-mediated transcriptional activation.

Structured PICO

P

Population

Mice fed a high cholesterol diet and HepG2 cells (human hepatocellular carcinoma cell line)

I

Intervention

LXR-selective agonists (including oral T0901317 in mice)

O

Outcome

Angptl3 mRNA expression and promoter activitysurrogate

Implication

The study demonstrates that Angptl3 is a direct transcriptional target of LXR, providing a novel mechanism for LXR-mediated regulation of lipid metabolism.

Abstract

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Cite This Study

Kaplan et al. (2003) studied this question.

synapsesocial.com/papers/6a1e7d9d25b49a996c68f22b https://doi.org/10.1194/jlr.m200367-jlr200

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Regulation of the angiopoietin-like protein 3 gene by LXR

Key Points

Structured PICO

Implication

Abstract

Discussion

Cite This Study

Regulation of the angiopoietin-like protein 3 gene by LXR

Key Points

Structured PICO

Implication

Abstract

Discussion

Cite This Study

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