Evidence for involvement of the alcohol consumption WDPCP gene in lipid metabolism, and liver cirrhosis.
Evidence for involvement of the alcohol consumption WDPCP gene in lipid metabolism, and liver cirrhosis.
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DOI：
10.1038/s41598-023-47371-7
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发表时间：
2023-11-23
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
酒精消耗和酒精性肝病（ALD）之间的生物学途径尚未完全了解。我们选择了已知对（1）饮酒，（2）肝功能和（3）基因表达有影响的基因。这些基因在秀丽隐杆线虫和黑腹果蝇中的直向同源物的表达使用突变和/或RNA干扰（RNAi）被抑制。在人类中，进行关联分析、途径分析和孟德尔随机化分析，以确定饮酒引起的代谢变化。In C.在线虫中，我们发现暴露于乙醇后ACTR 1B和MAPT的RNAi敲低的运动速率降低。在果蝇中，我们观察到（1）RNAi敲除WDPCP、TENM 2、GPN 1、ARPC 1B和SCN 8A的乙醇镇静作用的变化，（2）RNAi敲除TENM 2的乙醇消耗减少，（3）RNAi敲除WDPCP、TENM 2和GPN 1的三自由基甘油（TAG）水平降低。在人类中，我们观察到（1）饮酒与包括TAG在内的几种代谢物之间的联系，（2）亚油酸（LNA）和α-亚麻酸（ALA）代谢途径中候选（酒精相关）代谢物的富集，（3）WDPCP基因表达与肝纤维化和肝硬化之间的因果关系。我们的研究结果表明，WDPCP可能参与ALD。
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.
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影响因子：
5.2
作者：
Forsythe, Elizabeth;Beales, Philip L.
通讯作者：
Beales, Philip L.
影响因子：
4.4
作者：
Chadeau-Hyam, Marc;Ebbels, Timothy M. D.;Brown, Ian J.;Chan, Queenie;Stemler, Jeremiah;Huang, Chiang Ching;Daviglus, Martha L.;Ueshima, Hirotsugu;Zhao, Liancheng;Holmes, Elaine;Nicholson, Jeremy K.;Elliott, Paul;De Iorio, Maria
通讯作者：
De Iorio, Maria
影响因子：
14.9
作者：
Jewison T;Su Y;Disfany FM;Liang Y;Knox C;Maciejewski A;Poelzer J;Huynh J;Zhou Y;Arndt D;Djoumbou Y;Liu Y;Deng L;Guo AC;Han B;Pon A;Wilson M;Rafatnia S;Liu P;Wishart DS
通讯作者：
Wishart DS
影响因子：
9.8
作者：
Cui C;Chatterjee B;Lozito TP;Zhang Z;Francis RJ;Yagi H;Swanhart LM;Sanker S;Francis D;Yu Q;San Agustin JT;Puligilla C;Chatterjee T;Tansey T;Liu X;Kelley MW;Spiliotis ET;Kwiatkowski AV;Tuan R;Pazour GJ;Hukriede NA;Lo CW
通讯作者：
Lo CW
影响因子：
1.2
作者：
Diegelmann, Soeren;Jansen, Annika;Scholz, Henrike
通讯作者：
Scholz, Henrike