Evidence for Involvement of WDPCP Gene in Alcohol Consumption, Lipid Metabolism, and Liver Cirrhosis
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Le résumé fourni par la source
Abstract Alcohol consumption continues to cause a significant health burden globally. The advent of genome-wide association studies has unraveled many genetic loci associated with alcohol consumption. However, the biological effect of these loci and the pathways involved in alcohol consumption and its health consequences such as alcohol liver disease (ALD) remain to be elucidated. We combined human studies with model organisms Drosophila melanogaster and Caenorhabditis elegans to shed light on the molecular mechanisms underlying alcohol consumption and the health outcomes caused by alcohol intake. Using genetics and metabolite data within the Airwave study, a sample of police forces in the UK, we performed several analyses to identify changes in circulating metabolites that are triggered by alcohol consumption. We selected a set of genes annotated to genetic variants that are (1) known to be implicated in alcohol consumption, (2) are linked to liver function, and (3) are associated with expression (cis-eQTL) of their annotated genes. We used mutations and/or RNA interference (RNAi) to suppress the expression of these genes in C. elegans and Drosophila . We examined the effect of this suppression on ethanol consumption and on the sedative effects of ethanol. We also investigated the alcohol-induced changes in triacylglycerol (TGA) levels in Drosophila and tested differences in locomotion of C. elegans after acute exposure to ethanol. In human population, we found an enrichment of the alcohol-associated metabolites within the linoleic acid (LNA) and alpha linolenic acid (ALA) metabolism pathway. We further showed the effect of ACTR1B and MAPT on locomotion in C. elegans after exposure to ethanol. We demonstrated that three genes namely WDPCP, TENM2 and GPN1 modify TAG levels in Drosophila . Finally, we showed that gene expression of WDPCP in human population is linked to liver fibrosis and liver cirrhosis. Our results underline the impact of alcohol consumption on metabolism of lipids and pinpoints WDPCP as a gene with potential impact on fat accumulation upon exposure to ethanol suggesting a possible pathway to ALD.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Evidence for Involvement of <i>WDPCP</i> Gene in Alcohol Consumption, Lipid Metabolism, and Liver Cirrhosis
- Date Crossref
- 12/04/2023
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Brunel University of London pays non établi dans la noticeUniversité ou école supérieure
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The Francis Crick Institute pays non établi dans la noticeStructure de recherche
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UK Dementia Research Institute pays non établi dans la noticeStructure de recherche
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Imperial College London UK Dementia Research Institute pays non établi dans la noticeUniversité ou école supérieure
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MRC Centre for Environment and Health pays non établi dans la noticeStructure de recherche
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Health Data Research UK pays non établi dans la noticeOrganisation à but non lucratif
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Academy of Athens pays non établi dans la noticeUniversité ou école supérieure
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University of Cambridge MRC Toxicology Unit pays non établi dans la noticeUniversité ou école supérieure
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MRC Toxicology Unit pays non établi dans la noticeStructure de recherche
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University of Liverpool Department of Molecular Physiology and Cell Signalling pays non établi dans la noticeUniversité ou école supérieure
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College of Health and Life Sciences Department of Life Sciences pays non établi dans la noticeUniversité ou école supérieure
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School of Public Health Department of Epidemiology and Biostatistics pays non établi dans la noticeUniversité ou école supérieure
Brunel University of London, The Francis Crick Institute et UK Dementia Research Institute, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.