Evidence for involvement of the alcohol consumption WDPCP gene in lipid metabolism, and liver cirrhosis.

Animals Humans Alcohol Drinking / genetics Caenorhabditis elegans / genetics Drosophila melanogaster / genetics Ethanol / metabolism Lipid Metabolism / genetics Liver / metabolism Liver Cirrhosis / pathology Liver Diseases, Alcoholic / metabolism

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
23 Nov 2023
Historique:
received: 16 06 2023
accepted: 13 11 2023
medline: 27 11 2023
pubmed: 24 11 2023
entrez: 23 11 2023
Statut: epublish

Résumé

Biological pathways between alcohol consumption and alcohol liver disease (ALD) are not fully understood. We selected genes with known effect on (1) alcohol consumption, (2) liver function, and (3) gene expression. Expression of the orthologs of these genes in Caenorhabditis elegans and Drosophila melanogaster was suppressed using mutations and/or RNA interference (RNAi). In humans, association analysis, pathway analysis, and Mendelian randomization analysis were performed to identify metabolic changes due to alcohol consumption. In C. elegans, we found a reduction in locomotion rate after exposure to ethanol for RNAi knockdown of ACTR1B and MAPT. In Drosophila, we observed (1) a change in sedative effect of ethanol for RNAi knockdown of WDPCP, TENM2, GPN1, ARPC1B, and SCN8A, (2) a reduction in ethanol consumption for RNAi knockdown of TENM2, (3) a reduction in triradylglycerols (TAG) levels for RNAi knockdown of WDPCP, TENM2, and GPN1. In human, we observed (1) a link between alcohol consumption and several metabolites including TAG, (2) an enrichment of the candidate (alcohol-associated) metabolites within the linoleic acid (LNA) and alpha-linolenic acid (ALA) metabolism pathways, (3) a causal link between gene expression of WDPCP to liver fibrosis and liver cirrhosis. Our results imply that WDPCP might be involved in ALD.

Identifiants

DOI: 10.1038/s41598-023-47371-7 PMID: 37996473 PMC: PMC10667215
pubmed: 37996473
doi: 10.1038/s41598-023-47371-7
pii: 10.1038/s41598-023-47371-7
pmc: PMC10667215
doi:

Substances chimiques

Ethanol 3K9958V90M
WD repeat containing planar cell polarity effector 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

20616

Subventions

Organisme : Medical Research Council
ID : MR/R026505/2
Pays : United Kingdom

Informations de copyright

© 2023. The Author(s).

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Auteurs

Felix O'Farrell (F)

Cardiovascular and Metabolic Research Group, Division of Biosciences, Department of Life Sciences, College of Health and Life Sciences, Brunel University, London, UB8 3PH, UK.

Benjamin Aleyakpo (B)

The Francis Crick Institute, London, NW1 1AT, UK.

Rima Mustafa (R)

Department of Epidemiology and Biostatistics, School of Public Health, St Mary's Campus, Imperial College London, Norfolk Place, London, W2 1PG, UK.
UK Dementia Research Institute, Imperial College London, Exhibition Road, London, SW7 2AZ, UK.

Xiyun Jiang (X)

Cardiovascular and Metabolic Research Group, Division of Biosciences, Department of Life Sciences, College of Health and Life Sciences, Brunel University, London, UB8 3PH, UK.

Rui Climaco Pinto (RC)

Department of Epidemiology and Biostatistics, School of Public Health, St Mary's Campus, Imperial College London, Norfolk Place, London, W2 1PG, UK.
MRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, St Mary's Campus, Imperial College London, Norfolk Place, London, W2 1PG, UK.

Paul Elliott (P)

Department of Epidemiology and Biostatistics, School of Public Health, St Mary's Campus, Imperial College London, Norfolk Place, London, W2 1PG, UK.
UK Dementia Research Institute, Imperial College London, Exhibition Road, London, SW7 2AZ, UK.
MRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, St Mary's Campus, Imperial College London, Norfolk Place, London, W2 1PG, UK.
British Heart Foundation Centre of Research Excellence, Imperial College London, Du Cane Road, W12 0NN, UK.
National Institute for Health Research, Imperial Biomedical Research Centre, Imperial College London, Exhibition Road, London, SW7 2AZ, UK.
Health Data Research UK at Imperial College London, Exhibition Road, London, SW7 2AZ, UK.

Ioanna Tzoulaki (I)

Department of Epidemiology and Biostatistics, School of Public Health, St Mary's Campus, Imperial College London, Norfolk Place, London, W2 1PG, UK.
Centre for Systems Biology, Biomedical Research Foundation, Academy of Athens, Athens, Greece.

Abbas Dehghan (A)

Department of Epidemiology and Biostatistics, School of Public Health, St Mary's Campus, Imperial College London, Norfolk Place, London, W2 1PG, UK.
UK Dementia Research Institute, Imperial College London, Exhibition Road, London, SW7 2AZ, UK.
MRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, St Mary's Campus, Imperial College London, Norfolk Place, London, W2 1PG, UK.

Samantha H Y Loh (SHY)

MRC Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge, CB2 1QR, UK.

Jeff W Barclay (JW)

Department of Molecular Physiology and Cell Signalling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 3BX, UK.

L Miguel Martins (LM)

MRC Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge, CB2 1QR, UK.

Raha Pazoki (R)

Cardiovascular and Metabolic Research Group, Division of Biosciences, Department of Life Sciences, College of Health and Life Sciences, Brunel University, London, UB8 3PH, UK. raha.pazoki@brunel.ac.uk.
Department of Epidemiology and Biostatistics, School of Public Health, St Mary's Campus, Imperial College London, Norfolk Place, London, W2 1PG, UK. raha.pazoki@brunel.ac.uk.
Division of Biomedical Sciences, Department of Life Sciences, College of Health and Life Sciences, Brunel University, London, UB8 3PH, UK. raha.pazoki@brunel.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Evidence for involvement of the alcohol...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Evidence for involvement of the alcohol...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Comportement › Comportement dipsique › Consommation d'alcool › Evidence for involvement of the alcohol...
questionsmedicales.fr › Eucaryotes › Animaux › Invertébrés › Helminthes › Nematoda › Chromadorea › Rhabditida › Rhabditoidea › Caenorhabditis › Caenorhabditis elegans › Evidence for involvement of the alcohol...
questionsmedicales.fr › Eucaryotes › Animaux › Invertébrés › Arthropodes › Insectes › Pterygota › Neoptera › Holometabola › Diptera › Drosophilidae › Drosophila › Drosophila melanogaster › Evidence for involvement of the alcohol...
questionsmedicales.fr › Composés chimiques organiques › Alcools › Éthanol › Evidence for involvement of the alcohol...
questionsmedicales.fr › Métabolisme › Métabolisme lipidique › Evidence for involvement of the alcohol...
questionsmedicales.fr › Système digestif › Foie › Evidence for involvement of the alcohol...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Fibrose › Cirrhose du foie › Evidence for involvement of the alcohol...
questionsmedicales.fr › Troubles dus à des produits chimiques › Troubles dus à l'abus d'alcool › Maladies alcooliques du foie › Evidence for involvement of the alcohol...