Evidence map›Paper›PMID 27251289›Full record

ArticleNature2016

Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis.

Tamer Sallam, Marius C Jones, Thomas Gilliland, Li Zhang, Xiaohui Wu, Ascia Eskin, Jaspreet Sandhu, David Casero, Thomas Q de Aguiar Vallim, Cynthia Hong and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
145citing papers in PubMed, 2 pooled it
25.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

145 citing papers in PubMed, 2 syntheses or guidelines pooled it, 210 citations in OpenAlex.

  1. Effect of 9p21.3 (lncRNA and CDKN2A/2B) variant on lipid profile.Frontiers in cardiovascular medicine · 2022
    Pooled it
  2. Pooled it
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  16. Advances in the Regulation of Lipid Metabolism by Non-Coding RNAs.Animals : an open access journal from MDPI · 2025
    Review
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  18. Article
  19. Review
  20. Review

85 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Tamer SallamDepartment of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles, California 90095, USA.
Marius C JonesDepartment of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles, California 90095, USA.
Thomas GillilandDepartment of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles, California 90095, USA.
Li ZhangDepartment of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles, California 90095, USA.
Xiaohui WuDepartment of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles, California 90095, USA.
Ascia EskinDepartement of Human Genetics, University of California, Los Angeles, California 90095, USA.
Jaspreet SandhuDepartment of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles, California 90095, USA.
David CaseroDepartment of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles, California 90095, USA.
Thomas Q de Aguiar VallimDepartment of Medicine, Division of Cardiology, University of California, Los Angeles, California 90095, USA.
Cynthia HongDepartment of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles, California 90095, USA.
Melanie KatzIonis Pharmaceuticals, Carlsbad, California 92008, USA.
Richard LeeIonis Pharmaceuticals, Carlsbad, California 92008, USA.
Julian WhiteleggePasarow Mass Spectrometry Laboratory, NPI-Semel Institute, University of California, Los Angeles, California 90095, USA.
Peter TontonozDepartment of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles, California 90095, USA.
Howard Hughes Medical Institute · USUniversity of California, Los Angeles · USIonis Pharmaceuticals (United States) · US

Funding

ULTRASTRUCTURE OF THE INTIMA IN EARLY LESION FORMATIONP01HL030568 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FOGELMAN, ALAN M · 1985 to 2019
$55.2M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
The Lipin Protein Family and Triglyceride Metabolism P01HL090553 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YOUNG, STEPHEN G. · 2008 to 2018
$23.3M
CARDIOVASCULAR SCIENTIST TRAINING PROGRAMT32HL007895 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SHIVKUMAR, KALYANAM, WATSON, KAROL E · 1998 to 2023
$9.2M
Vascular Biology Training GrantT32HL069766 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 2002 to 2022
$7.4M
NUCLEAR RECEPTOR SIGNALING PATHWAYS IN ATHEROGENESISR01HL066088 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TONTONOZ, PETER J · 2001 to 2018
$5.4M
Novel transcriptional regulators of bile acid metabolism and hepatotoxicityR01DK102559 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EDWARDS, PETER A · 2014 to 2017
$1.3M
Long Non-coding RNAs in Cardiometabolic DiseaseK08HL128822 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SALLAM, TAMER · 2015 to 2019
$884k
Howard Hughes Medical InstituteNHLBI NIH HHS HL030568NHLBI NIH HHS HL066088NHLBI NIH HHS HL128822NHLBI NIH HHS HL69766NHLBI NIH HHS K08 HL128822NHLBI NIH HHS P01 HL030568NHLBI NIH HHS P01 HL090553NHLBI NIH HHS R01 HL066088NHLBI NIH HHS T32 HL007895NHLBI NIH HHS T32 HL069766NIDDK NIH HHS DK063491NIDDK NIH HHS DK102559NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK102559
6 · The paper itself

Abstract

Liver X receptors (LXRs) are transcriptional regulators of cellular and systemic cholesterol homeostasis. Under conditions of excess cholesterol, LXR activation induces the expression of several genes involved in cholesterol efflux, facilitates cholesterol esterification by promoting fatty acid synthesis, and inhibits cholesterol uptake by the low-density lipoprotein receptor. The fact that sterol content is maintained in a narrow range in most cell types and in the organism as a whole suggests that extensive crosstalk between regulatory pathways must exist. However, the molecular mechanisms that integrate LXRs with other lipid metabolic pathways are incompletely understood. Here we show that ligand activation of LXRs in mouse liver not only promotes cholesterol efflux, but also simultaneously inhibits cholesterol biosynthesis. We further identify the long non-coding RNA LeXis as a mediator of this effect. Hepatic LeXis expression is robustly induced in response to a Western diet (high in fat and cholesterol) or to pharmacological LXR activation. Raising or lowering LeXis levels in the liver affects the expression of genes involved in cholesterol biosynthesis and alters the cholesterol levels in the liver and plasma. LeXis interacts with and affects the DNA interactions of RALY, a heterogeneous ribonucleoprotein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the mouse liver. These findings outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms that coordinate sterol homeostasis.

Indexed as

AnimalsCholesterolDietary FatsDiet, WesternGene Expression RegulationHeterogeneous-Nuclear Ribonucleoprotein Group CHomeostasisLigandsLipid MetabolismLiverLiver X ReceptorsMaleMiceMice, Inbred C57BLOrphan Nuclear ReceptorsRNA, Long NoncodingCholesterolDietary FatsHeterogeneous-Nuclear Ribonucleoprotein Group CLigandsLiver X ReceptorsOrphan Nuclear ReceptorsRaly protein, mouseRNA, Long NoncodingSterol Regulatory Element Binding Proteins

Identifiers

PMID27251289
PMCPMC4896091
OpenAlexW2348844796

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.