Evidence map›Paper›PMID 36241646›Full record

ArticleNature communications2022

TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis.

Kasparas Petkevicius, Henrik Palmgren, Matthew S Glover, Andrea Ahnmark, Anne-Christine Andréasson, Katja Madeyski-Bengtson, Hiroki Kawana, Erik L Allman, Delaney Kaper, Martin Uhrbom and 19 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

17 citing papers in PubMed, 20 citations in OpenAlex.

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  16. Multi-omics analysis of TLCD1 as a promising biomarker in pan-cancer.Frontiers in cell and developmental biology · 2023
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  17. Review
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

29 authors at 6 institutions in 4 countries.

Kasparas PetkeviciusBioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. kasparas.petkevicius@astrazeneca.com.ORCID 0000-0003-2295-6065
Henrik PalmgrenBioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Matthew S GloverDynamic Omics, Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Andrea AhnmarkBioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Anne-Christine AndréassonBioscience Cardiovascular, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Katja Madeyski-BengtsonDiscovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Hiroki KawanaDepartment of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Erik L AllmanDynamic Omics, Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Delaney KaperDepartment of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.ORCID 0000-0002-9929-8104
Martin UhrbomBioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Liselotte AnderssonClinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Leif AasehaugBioscience Cardiovascular, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Johan ForsströmDiscovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Simonetta WallinBioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0001-5668-1229
Ingela AhlstedtBioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Renata LekeBioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Daniel KarlssonBioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Hernán González-KingBioscience Cardiovascular, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0003-4344-9484
Lars LöfgrenTranslational Science and Experimental Medicine, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Ralf NilssonTranslational Science and Experimental Medicine, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Giovanni PellegriniClinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Nozomu KonoDepartment of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.ORCID 0000-0002-0871-8477
Junken AokiDepartment of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Sonja HessDynamic Omics, Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Grzegorz SienskiDiscovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0002-2730-7710
Marc PilonDepartment of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.ORCID 0000-0003-3919-2882
Mohammad Bohlooly-YDiscovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Marcello MarescaDiscovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0003-0796-661X
Xiao-Rong PengBioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
AstraZeneca (Sweden) · SEAstraZeneca (United States) · USJapan Agency for Medical Research and Development · JPUniversity of Gothenburg · SEAstraZeneca (Japan) · JPThe University of Tokyo · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition. We generated Tlcd1/2 double-knockout (DKO) mice and found that they have reduced levels of hepatic monounsaturated fatty acid (MUFA)-containing PE species. Mechanistically, TLCD1/2 proteins act cell intrinsically to promote the incorporation of MUFAs into PEs. Furthermore, TLCD1/2 interact with the mitochondria in an evolutionarily conserved manner and regulate mitochondrial PE composition. Lastly, we demonstrate the biological relevance of our findings in dietary models of metabolic disease, where Tlcd1/2 DKO mice display attenuated development of non-alcoholic steatohepatitis compared to controls. Overall, we identify TLCD1/2 proteins as key regulators of cellular PE composition, with our findings having broad implications in understanding and treating disease.

Indexed as

Non-alcoholic Fatty Liver DiseasePhosphatidylethanolaminesAnimalsFatty AcidsFatty Acids, MonounsaturatedLiverMiceMice, Inbred C57BLMice, KnockoutFatty AcidsFatty Acids, MonounsaturatedPhosphatidylethanolamines

Identifiers

PMID36241646
PMCPMC9568529
OpenAlexW4306168810

What OpenQuestion holds

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LicenceCC BY
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.