• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

有证据表明，饮酒 WDPCP 基因参与脂质代谢和肝硬化。

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

机构信息

Cardiovascular and Metabolic Research Group, Division of Biosciences, Department of Life Sciences, College of Health and Life Sciences, Brunel University, London, UB8 3PH, UK.

The Francis Crick Institute, London, NW1 1AT, UK.

出版信息

Sci Rep. 2023 Nov 23;13(1):20616. doi: 10.1038/s41598-023-47371-7.

DOI:10.1038/s41598-023-47371-7
PMID:37996473
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10667215/
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.

摘要

酒精摄入与酒精性肝病（ALD）之间的生物学途径尚未完全阐明。我们选择了已知对（1）酒精摄入、（2）肝功能和（3）基因表达有影响的基因。使用突变和/或 RNA 干扰（RNAi）来抑制这些基因在秀丽隐杆线虫和黑腹果蝇中的同源物的表达。在人类中，进行了关联分析、途径分析和孟德尔随机化分析，以确定由于酒精摄入而导致的代谢变化。在秀丽隐杆线虫中，我们发现暴露于乙醇后，通过 ACTR1B 和 MAPT 的 RNAi 敲低，运动率降低。在果蝇中，我们观察到（1）WDPCP、TENM2、GPN1、ARPC1B 和 SCN8A 的 RNAi 敲低对乙醇镇静作用的改变，（2）TENM2 的 RNAi 敲低导致乙醇消耗减少，（3）WDPCP、TENM2 和 GPN1 的 RNAi 敲低导致三酰基甘油（TAG）水平降低。在人类中，我们观察到（1）酒精摄入与包括 TAG 在内的几种代谢物之间存在关联，（2）候选（与酒精相关）代谢物在亚油酸（LNA）和α-亚麻酸（ALA）代谢途径中富集，（3）WDPCP 的基因表达与肝纤维化和肝硬化之间存在因果关系。我们的结果表明，WDPCP 可能与 ALD 有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0312/10667215/97fee136c466/41598_2023_47371_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0312/10667215/35fd125f0fe1/41598_2023_47371_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0312/10667215/b0e674189722/41598_2023_47371_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0312/10667215/97fee136c466/41598_2023_47371_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0312/10667215/35fd125f0fe1/41598_2023_47371_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0312/10667215/b0e674189722/41598_2023_47371_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0312/10667215/97fee136c466/41598_2023_47371_Fig3_HTML.jpg

相似文献

1
Evidence for involvement of the alcohol consumption WDPCP gene in lipid metabolism, and liver cirrhosis.有证据表明，饮酒 WDPCP 基因参与脂质代谢和肝硬化。
Sci Rep. 2023 Nov 23;13(1):20616. doi: 10.1038/s41598-023-47371-7.
2
Pathophysiological Aspects of Alcohol Metabolism in the Liver.酒精在肝脏中的代谢的病理生理学方面。
Int J Mol Sci. 2021 May 27;22(11):5717. doi: 10.3390/ijms22115717.
3
Pathogenesis of alcoholic liver disease: role of oxidative metabolism.酒精性肝病的发病机制：氧化代谢的作用。
World J Gastroenterol. 2014 Dec 21;20(47):17756-72. doi: 10.3748/wjg.v20.i47.17756.
4
Preventive effect of low-carbohydrate high-fat dietary pattern on liver disease caused by alcohol consumption a 6pgd-involved mechanism in mice.低碳水化合物高脂肪膳食模式对酒精性肝病的预防作用：小鼠中 6PGD 相关机制。
Food Funct. 2024 Jan 22;15(2):732-746. doi: 10.1039/d3fo04335e.
5
Smoking, alcohol consumption, and 24 gastrointestinal diseases: Mendelian randomization analysis.吸烟、饮酒与 24 种胃肠道疾病：孟德尔随机化分析。
Elife. 2023 Feb 2;12:e84051. doi: 10.7554/eLife.84051.
6
Ethanol and unsaturated dietary fat induce unique patterns of hepatic ω-6 and ω-3 PUFA oxylipins in a mouse model of alcoholic liver disease.乙醇和不饱和膳食脂肪在酒精性肝病的小鼠模型中诱导独特的肝ω-6 和 ω-3 PUFA 氧化产物模式。
PLoS One. 2018 Sep 26;13(9):e0204119. doi: 10.1371/journal.pone.0204119. eCollection 2018.
7
Insulin-like growth factor-binding protein 7 exacerbates inflammatory response and lipid metabolism imbalance in alcohol-associated liver disease.胰岛素样生长因子结合蛋白 7 加剧酒精性肝病中的炎症反应和脂质代谢失衡。
Free Radic Biol Med. 2024 Nov 1;224:809-821. doi: 10.1016/j.freeradbiomed.2024.09.006. Epub 2024 Sep 17.
8
Fatty Liver Disease-Alcoholic and Non-Alcoholic: Similar but Different.非酒精性与酒精性脂肪性肝病：相似但不同。
Int J Mol Sci. 2022 Dec 19;23(24):16226. doi: 10.3390/ijms232416226.
9
Phospholipase D2 drives cellular lipotoxicity and tissue inflammation in alcohol-associated liver disease.磷脂酶 D2 驱动酒精相关性肝病中的细胞脂肪毒性和组织炎症。
Life Sci. 2024 Dec 1;358:123166. doi: 10.1016/j.lfs.2024.123166. Epub 2024 Oct 22.
10
Immune dysregulation and pathophysiology of alcohol consumption and alcoholic liver disease.免疫失调与酒精摄入和酒精性肝病的病理生理学。
Rev Gastroenterol Mex (Engl Ed). 2023 Apr-Jun;88(2):136-154. doi: 10.1016/j.rgmxen.2023.03.003. Epub 2023 Mar 25.

引用本文的文献

1
Comparative Transcriptome Analysis of Hens' Livers in Conventional Cage vs. Cage-Free Egg Production Systems.传统笼养与散养蛋鸡生产系统中母鸡肝脏的转录组比较分析
Vet Med Int. 2025 Mar 21;2025:3041254. doi: 10.1155/vmi/3041254. eCollection 2025.
2
A cross-tissue transcriptome-wide association study identifies WDPCP as a potential susceptibility gene for coronary atherosclerosis.一项跨组织全转录组关联研究确定WDPCP是冠状动脉粥样硬化的潜在易感基因。
Atheroscler Plus. 2024 Nov 23;58:59-74. doi: 10.1016/j.athplu.2024.11.002. eCollection 2024 Dec.

本文引用的文献

1
Genes regulating levels of ω-3 long-chain polyunsaturated fatty acids are associated with alcohol use disorder and consumption, and broader externalizing behavior in humans.调节ω-3 长链多不饱和脂肪酸水平的基因与人类的酒精使用障碍和消费，以及更广泛的外在行为有关。
Alcohol Clin Exp Res. 2022 Sep;46(9):1657-1664. doi: 10.1111/acer.14916. Epub 2022 Aug 7.
2
Molecular Alterations Caused by Alcohol Consumption in the UK Biobank: A Mendelian Randomisation Study.饮酒导致的英国生物库中分子改变：一项孟德尔随机化研究。
Nutrients. 2022 Jul 19;14(14):2943. doi: 10.3390/nu14142943.
3
Urinary Sodium Excretion Enhances the Effect of Alcohol on Blood Pressure.
尿钠排泄增强酒精对血压的影响。
Healthcare (Basel). 2022 Jul 13;10(7):1296. doi: 10.3390/healthcare10071296.
4
Impaired reciprocal regulation between SIRT6 and TGF-β signaling in fatty liver.脂肪肝病中 SIRT6 和 TGF-β 信号的相互调节受损。
FASEB J. 2022 Jun;36(6):e22335. doi: 10.1096/fj.202101518R.
5
Hepatocyte TGF-β Signaling Inhibiting WAT Browning to Promote NAFLD and Obesity Is Associated With Let-7b-5p.肝细胞 TGF-β 信号抑制 WAT 褐变促进 NAFLD 和肥胖与 Let-7b-5p 相关。
Hepatol Commun. 2022 Jun;6(6):1301-1321. doi: 10.1002/hep4.1892. Epub 2022 Jan 11.
6
Wdpcp regulates cellular proliferation and differentiation in the developing limb via hedgehog signaling.Wdpcp 通过 hedgehog 信号通路调节发育肢体中的细胞增殖和分化。
BMC Dev Biol. 2021 Jul 5;21(1):10. doi: 10.1186/s12861-021-00241-9.
7
Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.在欧洲血统个体中的遗传分析确定了 517 个与肝酶相关的位点。
Nat Commun. 2021 May 10;12(1):2579. doi: 10.1038/s41467-021-22338-2.
8
Increased dopaminergic neurotransmission results in ethanol dependent sedative behaviors in Caenorhabditis elegans.增加多巴胺能神经递质传递会导致秀丽隐杆线虫依赖乙醇的镇静行为。
PLoS Genet. 2021 Feb 1;17(2):e1009346. doi: 10.1371/journal.pgen.1009346. eCollection 2021 Feb.
9
G-protein αq gene expression plays a role in alcohol tolerance in .G蛋白αq基因表达在……的酒精耐受性中起作用。
Brain Neurosci Adv. 2019 Nov 1;3:2398212819883081. doi: 10.1177/2398212819883081. eCollection 2019 Jan-Dec.
10
Functional validity, role, and implications of heavy alcohol consumption genetic loci.重度饮酒相关遗传位点的功能有效性、作用及意义。
Sci Adv. 2020 Jan 15;6(3):eaay5034. doi: 10.1126/sciadv.aay5034. eCollection 2020 Jan.