酒精相关性脂肪肝中的脂滴相关蛋白:蛋白质组学方法

IF 3 Q2 SUBSTANCE ABUSE Alcohol (Hanover, York County, Pa.) Pub Date : 2024-11-01 Epub Date: 2024-10-16 DOI:10.1111/acer.15446
Sathish Kumar Perumal, Le Z Day, Madan Kumar Arumugam, Srinivas Chava, Vikas Kumar, Natalia A Osna, Jon Jacobs, Karuna Rasineni, Kusum K Kharbanda
{"title":"酒精相关性脂肪肝中的脂滴相关蛋白:蛋白质组学方法","authors":"Sathish Kumar Perumal, Le Z Day, Madan Kumar Arumugam, Srinivas Chava, Vikas Kumar, Natalia A Osna, Jon Jacobs, Karuna Rasineni, Kusum K Kharbanda","doi":"10.1111/acer.15446","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The earliest manifestation of alcohol-associated liver disease (ALD) is steatosis characterized by deposition of fat in specialized organelles called lipid droplets (LDs). While alcohol administration causes a rise in LD numbers in the hepatocytes, little is known regarding their characteristics that allow their accumulation and size to increase. The aim of the present study is to gain insights into underlying pathophysiological mechanisms by investigating the ethanol-induced changes in hepatic LD proteome as a function of LD size.</p><p><strong>Methods: </strong>Adult male Wistar rats (180-200 g BW) were fed with ethanol liquid diet for 6 weeks. At sacrifice, large-, medium-, and small-sized hepatic LD subpopulations (LD1, LD2, and LD3, respectively) were isolated and subjected to morphological and proteomic analyses.</p><p><strong>Results: </strong>Morphological analysis of LD1-LD3 fractions of ethanol-fed rats clearly demonstrated that LD1 contained larger LDs compared with LD2 and LD3 fractions. Our preliminary results from principal component analysis showed that the proteome of different-sized hepatic LD fractions was distinctly different. Proteomic data analysis identified over 2000 proteins in each LD fraction with significant alterations in protein abundance among the three LD fractions. Among the altered proteins, several were related to fat metabolism, including synthesis, incorporation of fatty acid, and lipolysis. Ingenuity pathway analysis revealed increased fatty acid synthesis, fatty acid incorporation, LD fusion, and reduced lipolysis in LD1 compared to LD3. Overall, the proteomic findings indicate that the increased level of protein that facilitates fusion of LDs combined with an increased association of negative regulators of lipolysis dictates the generation of large-sized LDs during the development of alcohol-associated hepatic steatosis.</p><p><strong>Conclusion: </strong>Several significantly altered proteins were identified in different-sized LDs isolated from livers of ethanol-fed rats. Ethanol-induced increases in specific proteins that hinder LD lipid metabolism led to the accumulation and persistence of large-sized LDs in the liver.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lipid droplet-associated proteins in alcohol-associated fatty liver disease: A proteomic approach.\",\"authors\":\"Sathish Kumar Perumal, Le Z Day, Madan Kumar Arumugam, Srinivas Chava, Vikas Kumar, Natalia A Osna, Jon Jacobs, Karuna Rasineni, Kusum K Kharbanda\",\"doi\":\"10.1111/acer.15446\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The earliest manifestation of alcohol-associated liver disease (ALD) is steatosis characterized by deposition of fat in specialized organelles called lipid droplets (LDs). While alcohol administration causes a rise in LD numbers in the hepatocytes, little is known regarding their characteristics that allow their accumulation and size to increase. The aim of the present study is to gain insights into underlying pathophysiological mechanisms by investigating the ethanol-induced changes in hepatic LD proteome as a function of LD size.</p><p><strong>Methods: </strong>Adult male Wistar rats (180-200 g BW) were fed with ethanol liquid diet for 6 weeks. At sacrifice, large-, medium-, and small-sized hepatic LD subpopulations (LD1, LD2, and LD3, respectively) were isolated and subjected to morphological and proteomic analyses.</p><p><strong>Results: </strong>Morphological analysis of LD1-LD3 fractions of ethanol-fed rats clearly demonstrated that LD1 contained larger LDs compared with LD2 and LD3 fractions. Our preliminary results from principal component analysis showed that the proteome of different-sized hepatic LD fractions was distinctly different. Proteomic data analysis identified over 2000 proteins in each LD fraction with significant alterations in protein abundance among the three LD fractions. Among the altered proteins, several were related to fat metabolism, including synthesis, incorporation of fatty acid, and lipolysis. Ingenuity pathway analysis revealed increased fatty acid synthesis, fatty acid incorporation, LD fusion, and reduced lipolysis in LD1 compared to LD3. Overall, the proteomic findings indicate that the increased level of protein that facilitates fusion of LDs combined with an increased association of negative regulators of lipolysis dictates the generation of large-sized LDs during the development of alcohol-associated hepatic steatosis.</p><p><strong>Conclusion: </strong>Several significantly altered proteins were identified in different-sized LDs isolated from livers of ethanol-fed rats. Ethanol-induced increases in specific proteins that hinder LD lipid metabolism led to the accumulation and persistence of large-sized LDs in the liver.</p>\",\"PeriodicalId\":72145,\"journal\":{\"name\":\"Alcohol (Hanover, York County, Pa.)\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Alcohol (Hanover, York County, Pa.)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1111/acer.15446\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"SUBSTANCE ABUSE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alcohol (Hanover, York County, Pa.)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1111/acer.15446","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/16 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"SUBSTANCE ABUSE","Score":null,"Total":0}
引用次数: 0

摘要

背景:酒精相关性肝病(ALD)的最早表现是脂肪变性,其特征是脂肪沉积在称为脂滴(LDs)的特殊细胞器中。虽然饮酒会导致肝细胞中的脂滴数量增加,但人们对其积累和体积增大的特征却知之甚少。本研究的目的是通过研究乙醇诱导的肝脏 LD 蛋白质组变化与 LD 大小的关系,深入了解潜在的病理生理机制:方法:成年雄性 Wistar 大鼠(体重 180-200 g)用乙醇液态食物喂养 6 周。牺牲时,分离大、中、小尺寸肝脏 LD 亚群(分别为 LD1、LD2 和 LD3)并进行形态学和蛋白质组分析:结果:对乙醇喂养大鼠的 LD1-LD3 组群进行的形态学分析清楚地表明,与 LD2 和 LD3 组群相比,LD1 组群含有较大的 LD。主成分分析的初步结果显示,不同大小的肝脏 LD 部分的蛋白质组明显不同。蛋白质组数据分析在每个 LD 组份中发现了 2000 多个蛋白质,三个 LD 组份的蛋白质丰度发生了显著变化。在改变的蛋白质中,有几种与脂肪代谢有关,包括合成、脂肪酸结合和脂肪分解。Ingenuity pathway 分析显示,与 LD3 相比,LD1 中的脂肪酸合成、脂肪酸掺入、LD 融合增加,而脂肪分解减少。总之,蛋白质组学研究结果表明,在酒精相关性肝脂肪变性的发展过程中,促进 LD 融合的蛋白质水平增加,加上脂肪分解负调控因子的关联增加,决定了大尺寸 LD 的产生:结论:从喂食乙醇的大鼠肝脏中分离出的不同大小的LDs中发现了几种明显改变的蛋白质。乙醇引起的阻碍LD脂质代谢的特定蛋白质的增加导致了大尺寸LD在肝脏中的积累和持续存在。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Lipid droplet-associated proteins in alcohol-associated fatty liver disease: A proteomic approach.

Background: The earliest manifestation of alcohol-associated liver disease (ALD) is steatosis characterized by deposition of fat in specialized organelles called lipid droplets (LDs). While alcohol administration causes a rise in LD numbers in the hepatocytes, little is known regarding their characteristics that allow their accumulation and size to increase. The aim of the present study is to gain insights into underlying pathophysiological mechanisms by investigating the ethanol-induced changes in hepatic LD proteome as a function of LD size.

Methods: Adult male Wistar rats (180-200 g BW) were fed with ethanol liquid diet for 6 weeks. At sacrifice, large-, medium-, and small-sized hepatic LD subpopulations (LD1, LD2, and LD3, respectively) were isolated and subjected to morphological and proteomic analyses.

Results: Morphological analysis of LD1-LD3 fractions of ethanol-fed rats clearly demonstrated that LD1 contained larger LDs compared with LD2 and LD3 fractions. Our preliminary results from principal component analysis showed that the proteome of different-sized hepatic LD fractions was distinctly different. Proteomic data analysis identified over 2000 proteins in each LD fraction with significant alterations in protein abundance among the three LD fractions. Among the altered proteins, several were related to fat metabolism, including synthesis, incorporation of fatty acid, and lipolysis. Ingenuity pathway analysis revealed increased fatty acid synthesis, fatty acid incorporation, LD fusion, and reduced lipolysis in LD1 compared to LD3. Overall, the proteomic findings indicate that the increased level of protein that facilitates fusion of LDs combined with an increased association of negative regulators of lipolysis dictates the generation of large-sized LDs during the development of alcohol-associated hepatic steatosis.

Conclusion: Several significantly altered proteins were identified in different-sized LDs isolated from livers of ethanol-fed rats. Ethanol-induced increases in specific proteins that hinder LD lipid metabolism led to the accumulation and persistence of large-sized LDs in the liver.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
5.40
自引率
0.00%
发文量
0
期刊最新文献
Santa Claus, the Tooth Fairy, and purported lifetime nondrinkers: Ramifications for observational evidence about alcohol and health. Alcohol hangovers as a predictor of the development of immune-related chronic diseases. Impaired or not impaired: The accuracy of the Montreal Cognitive Assessment in detecting cognitive impairment among patients with alcohol use disorder. Clinical characteristics of seizure recurrence and epilepsy development in patients with alcohol-related seizures. Closing the gaps in alcohol behavior change: A real-world study of a digital intervention.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1