RRC ID 80803
Author O'Farrell F, Aleyakpo B, Mustafa R, Jiang X, Pinto RC, Elliott P, Tzoulaki I, Dehghan A, Loh SHY, Barclay JW, Martins LM, Pazoki R.
Title Evidence for involvement of the alcohol consumption WDPCP gene in lipid metabolism, and liver cirrhosis.
Journal Sci Rep
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.
Volume 13(1)
Pages 20616
Published 2023-11-23
DOI 10.1038/s41598-023-47371-7
PII 10.1038/s41598-023-47371-7
PMID 37996473
PMC PMC10667215
MeSH Alcohol Drinking / genetics Animals Caenorhabditis elegans* / genetics Drosophila melanogaster* / genetics Ethanol / metabolism Humans Lipid Metabolism* / genetics Liver / metabolism Liver Cirrhosis / pathology Liver Diseases, Alcoholic* / metabolism
C.elegans tm4735