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

被引：2

作者：

O'Farrell, Felix ^{[1
]}

Aleyakpo, Benjamin ^{[2
]}

Mustafa, Rima ^{[3
,4
]}

Jiang, Xiyun ^{[1
]}

Pinto, Rui Climaco ^{[3
,5
]}

Elliott, Paul ^{[3
,4
,5
,6
,7
,8
]}

Tzoulaki, Ioanna ^{[3
,9
]}

Dehghan, Abbas ^{[3
,4
,5
]}

Loh, Samantha H. Y. ^{[10
]}

Barclay, Jeff W. ^{[11
]}

Martins, L. Miguel ^{[10
]}

Pazoki, Raha ^{[1
,3
,12
]}

机构：

[1] Brunel Univ, Coll Hlth & Life Sci, Dept Life Sci, Div Biosci,Cardiovasc & Metab Res Grp, London UB8 3PH, England

[2] Francis Crick Inst, London NW1 1AT, England

[3] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, St Marys Campus,Norfolk Pl, London W2 1PG, England

[4] Imperial Coll London, UK Dementia Res Inst, Exhibit Rd, London SW7 2AZ, England

[5] Imperial Coll London, MRC Ctr Environm & Hlth, Sch Publ Hlth, Dept Epidemiol & Biostat, St Marys Campus,Norfolk Pl, London W2 1PG, England

[6] Imperial Coll London, British Heart Fdn Ctr Res Excellence, Du Cane Rd, London W12 0NN, England

[7] Imperial Coll London, Natl Inst Hlth Res, Imperial Biomed Res Ctr, Exhibit Rd, London SW7 2AZ, England

[8] Imperial Coll London, Hlth Data Res UK, Exhibit Rd, London SW7 2AZ, England

[9] Acad Athens, Biomed Res Fdn, Ctr Syst Biol, Athens, Greece

[10] Univ Cambridge, MRC Toxicol Unit, Gleeson Bldg,Tennis Court Rd, Cambridge CB2 1QR, England

[11] Univ Liverpool, Inst Syst Mol & Integrat Biol, Dept Mol Physiol & Cell Signalling, Liverpool L69 3BX, England

[12] Brunel Univ, Coll Hlth & Life Sci, Dept Life Sci, Div Biomed Sci, London UB8 3PH, England

来源：

SCIENTIFIC REPORTS | 2023年 / 13卷 / 01期

基金：

英国医学研究理事会;

关键词：

BEHAVIORAL-RESPONSES; WIDE ASSOCIATION; DETERMINANTS; POLARITY; ETHANOL; BINDING;

D O I：

10.1038/s41598-023-47371-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

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