Evidence map›Paper›PMID 29361464›Full record

ArticleCell systems2018

Integration of Multi-omics Data from Mouse Diversity Panel Highlights Mitochondrial Dysfunction in Non-alcoholic Fatty Liver Disease.

Karthickeyan Chella Krishnan, Zeyneb Kurt, Rio Barrere-Cain, Simon Sabir, Aditi Das, Raquel Floyd, Laurent Vergnes, Yuqi Zhao, Nam Che, Sarada Charugundla and 10 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell systems, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed, 2 pooled it
13.0field-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

96 citing papers in PubMed, 2 syntheses or guidelines pooled it, 172 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  8. MicroRNA-21 is a potential therapeutic agent targetingMolecular therapy. Nucleic acids · 2025
    Article
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  13. Genome-scale models in human metabologenomics.Nature reviews. Genetics · 2025
    Review
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36 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 1 institution in 1 country.

Karthickeyan Chella KrishnanDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Zeyneb KurtDepartment of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA.
Rio Barrere-CainDepartment of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA.
Simon SabirDepartment of Psychology, College of Letters and Science, University of California, Los Angeles, CA, USA.
Aditi DasDepartment of Psychology, College of Letters and Science, University of California, Los Angeles, CA, USA.
Raquel FloydDepartment of Microbiology, Immunology and Molecular Genetics, College of Letters and Science, University of California, Los Angeles, CA, USA.
Laurent VergnesDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Yuqi ZhaoDepartment of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA.
Nam CheDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Sarada CharugundlaDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Hannah QiDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Zhiqiang ZhouDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Yonghong MengDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Calvin PanDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Marcus M SeldinDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Frode NorheimDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Simon HuiDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Karen ReueDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Aldons J LusisDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Department of Microbiology, Immunology and Molecular Genetics, College of Letters and Science, University of California, Los Angeles, CA, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. Electronic address: jlusis@mednet.ucla.edu.
Xia YangDepartment of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA; Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, CA, USA. Electronic address: xyang123@ucla.edu.
University of California, Los Angeles · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Systems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUE, KAREN · 1985 to 2019
$50.2M
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
DHA Reverses Gene Network Signatures of Fructose-induced Metabolic SyndromeR01DK104363 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIA · 2015 to 2019
$2.4M
XF24-3 Extracellular Flux AnalyzerS10RR026744 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUE, KAREN · 2010 to 2010
$168k
NCATS NIH HHS UL1 TR001881NCRR NIH HHS S10 RR026744NHLBI NIH HHS P01 HL028481NHLBI NIH HHS T32 HL007895NHLBI NIH HHS T32 HL069766NIDDK NIH HHS R01 DK104363
6 · The paper itself

Abstract

The etiology of non-alcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, is poorly understood. To understand the causal mechanisms underlying NAFLD, we conducted a multi-omics, multi-tissue integrative study using the Hybrid Mouse Diversity Panel, consisting of ∼100 strains of mice with various degrees of NAFLD. We identified both tissue-specific biological processes and processes that were shared between adipose and liver tissues. We then used gene network modeling to predict candidate regulatory genes of these NAFLD processes, including Fasn, Thrsp, Pklr, and Chchd6. In vivo knockdown experiments of the candidate genes improved both steatosis and insulin resistance. Further in vitro testing demonstrated that downregulation of both Pklr and Chchd6 lowered mitochondrial respiration and led to a shift toward glycolytic metabolism, thus highlighting mitochondria dysfunction as a key mechanistic driver of NAFLD.

Indexed as

AnimalsDatabases, GeneticGene Expression ProfilingGene Regulatory NetworksGenomicsHEK293 CellsHumansInsulin ResistanceLipid MetabolismLiverMaleMiceMice, Inbred C57BLMice, Inbred StrainsMitochondriaNon-alcoholic Fatty Liver DiseaseRibosomal Proteinsglycolysisintegrative genomicskey driver genesmitochondrial dysfunctionmouse diversity panelmulti-omics integrationnetwork modelingnon-alcoholic fatty liver diseaseoxidative phosphorylationsystems biology

Identifiers

PMID29361464
PMCPMC5799036
OpenAlexW2784764983

What OpenQuestion holds

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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.