Evidence map›Paper›PMID 34097992›Full record

ArticleToxicology2021

The aryl hydrocarbon receptor activates ceramide biosynthesis in mice contributing to hepatic lipogenesis.

Qing Liu, Limin Zhang, Erik L Allman, Troy D Hubbard, Iain A Murray, Fuhua Hao, Yuan Tian, Wei Gui, Robert G Nichols, Philip B Smith and 3 more

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

Article in Toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

13 citing papers in PubMed, 20 citations in OpenAlex.

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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

13 authors at 2 institutions in 2 countries.

Qing LiuCenter for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
Limin ZhangCAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences (CAS), Wuhan, 430071, China.
Erik L AllmanCenter for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
Troy D HubbardCenter for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
Iain A MurrayCenter for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
Fuhua HaoCenter for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
Yuan TianCenter for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
Wei GuiCenter for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
Robert G NicholsCenter for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
Philip B SmithHuck Institutes of the Life Sciences, University Park, PA, 16802, USA.
Mallappa AnithaCenter for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
Gary H PerdewCenter for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
Andrew D PattersonCenter for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, 16802, USA. Electronic address: adp117@psu.edu.
Pennsylvania State University · USChinese Academy of Sciences · CN

Funding

Activation of the Ah receptor and epithelial integrityR35ES028244 · NIEHS · PENNSYLVANIA STATE UNIVERSITY, THE · PI PERDEW, GARY H. · 2017 to 2024
$6.2M
REGULATION OF THE AH RECEPTORR01ES004869 · NIEHS · PURDUE UNIVERSITY WEST LAFAYETTE · PI PERDEW, GARY H. · 1994 to 2017
$5.3M
Optimized Metabolite Extraction, Separation, and Identification for MetabolomicsR01ES022186 · NIEHS · PENNSYLVANIA STATE UNIVERSITY, THE · PI PATTERSON, ANDREW · 2012 to 2016
$2.0M
Selective Ah Receptor Ligands Repress Acute-Phase ResponseR01ES019964 · NIEHS · PENNSYLVANIA STATE UNIVERSITY, THE · PI PERDEW, GARY H. · 2012 to 2016
$2.0M
Environmental Ah Receptor Ligand Impact on the Host-Microbiome Metabolic AxisR01ES028288 · NIEHS · PENNSYLVANIA STATE UNIVERSITY, THE · PI PATTERSON, ANDREW · 2017 to 2021
$1.7M
Acquisition of an Orbitrap Fusion Lumos Tribid Mass Spectrometer to Accelerate Metabolite Identification and Pathway AnalysisS10OD021750 · OD · PENNSYLVANIA STATE UNIVERSITY, THE · PI PATTERSON, ANDREW · 2017 to 2017
$966k
Environmental Ah Receptor Ligand Impact on the Host-Microbiome Metabolic AxisR56ES026684 · NIEHS · PENNSYLVANIA STATE UNIVERSITY, THE · PI PATTERSON, ANDREW · 2017 to 2017
$157k
NIEHS NIH HHS R01 ES004869NIEHS NIH HHS R01 ES019964NIEHS NIH HHS R01 ES022186NIEHS NIH HHS R01 ES028288NIEHS NIH HHS R35 ES028244NIEHS NIH HHS R56 ES026684NIH HHS S10 OD021750
6 · The paper itself

Abstract

Aryl hydrocarbon receptor (AHR) activation via 2,3,7,8-tetrachlorodibenzofuran (TCDF) induces the accumulation of hepatic lipids. Here we report that AHR activation by TCDF (24  μg/kg body weight given orally for five days) induced significant elevation of hepatic lipids including ceramides in mice, was associated with increased expression of key ceramide biosynthetic genes, and increased activity of their respective enzymes. Results from chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA) and cell-based reporter luciferase assays indicated that AHR directly activated the serine palmitoyltransferase long chain base subunit 2 (Sptlc2, encodes serine palmitoyltransferase 2 (SPT2)) gene whose product catalyzes the initial rate-limiting step in de novo sphingolipid biosynthesis. Hepatic ceramide accumulation was further confirmed by mass spectrometry-based lipidomics. Taken together, our results revealed that AHR activation results in the up-regulation of Sptlc2, leading to ceramide accumulation, thus promoting lipogenesis, which can induce hepatic lipid accumulation.

Indexed as

Activation, MetabolicAnimalsBasic Helix-Loop-Helix ProteinsBenzofuransCeramidesGene Expression RegulationHumansLipidomicsLipogenesisLiverMaleMiceMice, Inbred C57BLMice, KnockoutReceptors, Aryl HydrocarbonSerine C-Palmitoyltransferase2,3,7,8-tetrachlorodibenzofuranAhr protein, mouseBasic Helix-Loop-Helix ProteinsBenzofuransCeramidesReceptors, Aryl HydrocarbonSerine C-PalmitoyltransferaseSphingomyelin PhosphodiesteraseSptlc2 protein, mouseTriglyceridesAryl hydrocarbon receptor (AHR)CeramideLipogenesisSptlc2

Identifiers

PMID34097992
PMCPMC8327397
OpenAlexW3169709237

What Socratic 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 Socratic graph.