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



O'Farrell, Felix, Aleyakpo, Benjamin, Mustafa, Rima, Jiang, Xiyun, Pinto, Rui Climaco, Elliott, Paul, Tzoulaki, Ioanna, Dehghan, Abbas, Loh, Samantha HY, Barclay, Jeff W
et al (show 2 more authors) (2023) Evidence for involvement of the alcohol consumption WDPCP gene in lipid metabolism, and liver cirrhosis. Scientific reports, 13 (1). p. 20616.

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: Liver, Animals, Humans, Drosophila melanogaster, Caenorhabditis elegans, Liver Cirrhosis, Liver Diseases, Alcoholic, Ethanol, Alcohol Drinking, Lipid Metabolism
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 12 Dec 2023 10:12
Last Modified: 12 Dec 2023 10:12
DOI: 10.1038/s41598-023-47371-7
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3177274