心脏脂滴在病理和生理条件下是不同的。

IF 4.1 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ni-Huiping Son, Sunny Son, Michael Verano, Zhen-Xiu Liu, Waqas Younis, Makenzie Komack, Kelly V Ruggles, Jana Gjini, Song-Tao Tang, Ainara Gonzalez Cabodevilla, Feng-Xia Liang, Hai-Zhen Wang, Dimitrios Nasias, José O Alemán, Ira J Goldberg
{"title":"心脏脂滴在病理和生理条件下是不同的。","authors":"Ni-Huiping Son, Sunny Son, Michael Verano, Zhen-Xiu Liu, Waqas Younis, Makenzie Komack, Kelly V Ruggles, Jana Gjini, Song-Tao Tang, Ainara Gonzalez Cabodevilla, Feng-Xia Liang, Hai-Zhen Wang, Dimitrios Nasias, José O Alemán, Ira J Goldberg","doi":"10.1016/j.jlr.2025.100920","DOIUrl":null,"url":null,"abstract":"<p><p>Excessive accumulation of lipids within cardiomyocytes can sometimes initiate cardiomyopathy, while in other situations excess lipids do not cause harm. To understand how pathologic and non-pathologic lipid accumulation differ, we isolated lipid droplets (LDs) from two genetically altered mouse lines and from wild-type (WT) mice after an overnight fast. The LDs from MHC-peroxisomal proliferator-activated receptor γ1(MHC-Pparg1) transgenic mice were 3-fold larger than those from either fasted WT or non-cardiomyopathy MHC-diacylglycerol acyl transferase 1 (MHC-Dgat1) transgenic mice. Proteomic analysis of the LD associated membrane proteins (LDAMPs) showed that MHC-Pparg1 LDs had less perilipin (Plin). Proteins associated with lipolysis and LD formation (CIDEs and MTP), lipid synthesis, and Pparg signaling pathways were increased in MHC-Pparg1 LDAMPs. Unlike in MHC-Pparg1, MHC-Dgat1 LDAMPs exhibited increased mitochondrial peroxidative proteins with reduced adipose triglyceride lipase (Pnpla2), and Pparg coactivator 1 alpha (Pgc1A). Cardiomyocytes from MHC-Pparg1 hearts had transmission electron microscopy (TEM) images of ongoing lipolysis and greater amounts of lipolytic proteins. In contrast, images from MHC-Dgat1 cardiomyocytes showed more lipophagy. Consistent with the proteomic study and EM images, cardiac immunofluorescence staining showed that Plin 5 protein, thought to block LD lipolysis, was markedly reduced with MHC-Pparg1 overexpression, while hormone sensitive lipase was increased. The autophagosome marker protein LC3B was increased in MHC-Dgat1 but not in MHC-Pparg1 hearts. Potentially toxic lipids like diacylglycerols and ceramides were increased in hearts but not LDs from MHC-Pparg1 mice. Our data indicates that cardiomyocyte LDs vary in size, composition, and metabolism. Cardiotoxicity was associated with greater LD lipolysis, which we postulate leads to intracellular release of toxic lipids.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100920"},"PeriodicalIF":4.1000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cardiac lipid droplets differ under pathological and physiological conditions.\",\"authors\":\"Ni-Huiping Son, Sunny Son, Michael Verano, Zhen-Xiu Liu, Waqas Younis, Makenzie Komack, Kelly V Ruggles, Jana Gjini, Song-Tao Tang, Ainara Gonzalez Cabodevilla, Feng-Xia Liang, Hai-Zhen Wang, Dimitrios Nasias, José O Alemán, Ira J Goldberg\",\"doi\":\"10.1016/j.jlr.2025.100920\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Excessive accumulation of lipids within cardiomyocytes can sometimes initiate cardiomyopathy, while in other situations excess lipids do not cause harm. To understand how pathologic and non-pathologic lipid accumulation differ, we isolated lipid droplets (LDs) from two genetically altered mouse lines and from wild-type (WT) mice after an overnight fast. The LDs from MHC-peroxisomal proliferator-activated receptor γ1(MHC-Pparg1) transgenic mice were 3-fold larger than those from either fasted WT or non-cardiomyopathy MHC-diacylglycerol acyl transferase 1 (MHC-Dgat1) transgenic mice. Proteomic analysis of the LD associated membrane proteins (LDAMPs) showed that MHC-Pparg1 LDs had less perilipin (Plin). Proteins associated with lipolysis and LD formation (CIDEs and MTP), lipid synthesis, and Pparg signaling pathways were increased in MHC-Pparg1 LDAMPs. Unlike in MHC-Pparg1, MHC-Dgat1 LDAMPs exhibited increased mitochondrial peroxidative proteins with reduced adipose triglyceride lipase (Pnpla2), and Pparg coactivator 1 alpha (Pgc1A). Cardiomyocytes from MHC-Pparg1 hearts had transmission electron microscopy (TEM) images of ongoing lipolysis and greater amounts of lipolytic proteins. In contrast, images from MHC-Dgat1 cardiomyocytes showed more lipophagy. Consistent with the proteomic study and EM images, cardiac immunofluorescence staining showed that Plin 5 protein, thought to block LD lipolysis, was markedly reduced with MHC-Pparg1 overexpression, while hormone sensitive lipase was increased. The autophagosome marker protein LC3B was increased in MHC-Dgat1 but not in MHC-Pparg1 hearts. Potentially toxic lipids like diacylglycerols and ceramides were increased in hearts but not LDs from MHC-Pparg1 mice. Our data indicates that cardiomyocyte LDs vary in size, composition, and metabolism. Cardiotoxicity was associated with greater LD lipolysis, which we postulate leads to intracellular release of toxic lipids.</p>\",\"PeriodicalId\":16209,\"journal\":{\"name\":\"Journal of Lipid Research\",\"volume\":\" \",\"pages\":\"100920\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Lipid Research\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jlr.2025.100920\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Lipid Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.jlr.2025.100920","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

心肌细胞内脂质过度积累有时会引发心肌病,而在其他情况下,过量的脂质不会造成伤害。为了了解病理性和非病理性脂质积累的差异,我们从两种转基因小鼠品系和野生型小鼠(WT)中分离脂滴(ld),禁食一夜。mhc -过氧化物酶体增殖物激活受体γ - 1(MHC-Pparg1)转基因小鼠的ld比空腹WT或非心肌病mhc -二酰基甘油酰基转移酶1(MHC-Dgat1)转基因小鼠的ld大3倍。LD相关膜蛋白(LDAMPs)的蛋白质组学分析显示MHC-Pparg1 LD具有较少的perilipin (Plin)。在MHC-Pparg1 LDAMPs中,与脂肪分解和LD形成(CIDEs和MTP)、脂质合成和Pparg信号通路相关的蛋白质增加。与MHC-Pparg1不同,MHC-Dgat1 LDAMPs表现出线粒体过氧化蛋白增加,脂肪甘油三酯脂肪酶(Pnpla2)和Pparg共激活因子1 α (Pgc1A)减少。来自MHC-Pparg1心脏的心肌细胞有正在进行的脂肪分解的透射电子显微镜(TEM)图像和大量的脂肪分解蛋白。相比之下,MHC-Dgat1心肌细胞的图像显示更多的脂肪吞噬。与蛋白质组学研究和EM图像一致,心脏免疫荧光染色显示,被认为阻断LD脂肪分解的Plin 5蛋白明显减少,MHC-Pparg1过表达,而激素敏感脂肪酶升高。自噬体标记蛋白LC3B在MHC-Dgat1中升高,而在MHC-Pparg1中没有升高。MHC-Pparg1小鼠的心脏中潜在毒性脂质如二酰基甘油和神经酰胺增加,但LDs没有增加。我们的数据表明,心肌细胞ld在大小、组成和代谢方面各不相同。心脏毒性与更大的LD脂解有关,我们假设这导致细胞内释放有毒脂质。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cardiac lipid droplets differ under pathological and physiological conditions.

Excessive accumulation of lipids within cardiomyocytes can sometimes initiate cardiomyopathy, while in other situations excess lipids do not cause harm. To understand how pathologic and non-pathologic lipid accumulation differ, we isolated lipid droplets (LDs) from two genetically altered mouse lines and from wild-type (WT) mice after an overnight fast. The LDs from MHC-peroxisomal proliferator-activated receptor γ1(MHC-Pparg1) transgenic mice were 3-fold larger than those from either fasted WT or non-cardiomyopathy MHC-diacylglycerol acyl transferase 1 (MHC-Dgat1) transgenic mice. Proteomic analysis of the LD associated membrane proteins (LDAMPs) showed that MHC-Pparg1 LDs had less perilipin (Plin). Proteins associated with lipolysis and LD formation (CIDEs and MTP), lipid synthesis, and Pparg signaling pathways were increased in MHC-Pparg1 LDAMPs. Unlike in MHC-Pparg1, MHC-Dgat1 LDAMPs exhibited increased mitochondrial peroxidative proteins with reduced adipose triglyceride lipase (Pnpla2), and Pparg coactivator 1 alpha (Pgc1A). Cardiomyocytes from MHC-Pparg1 hearts had transmission electron microscopy (TEM) images of ongoing lipolysis and greater amounts of lipolytic proteins. In contrast, images from MHC-Dgat1 cardiomyocytes showed more lipophagy. Consistent with the proteomic study and EM images, cardiac immunofluorescence staining showed that Plin 5 protein, thought to block LD lipolysis, was markedly reduced with MHC-Pparg1 overexpression, while hormone sensitive lipase was increased. The autophagosome marker protein LC3B was increased in MHC-Dgat1 but not in MHC-Pparg1 hearts. Potentially toxic lipids like diacylglycerols and ceramides were increased in hearts but not LDs from MHC-Pparg1 mice. Our data indicates that cardiomyocyte LDs vary in size, composition, and metabolism. Cardiotoxicity was associated with greater LD lipolysis, which we postulate leads to intracellular release of toxic lipids.

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
Journal of Lipid Research
Journal of Lipid Research 生物-生化与分子生物学
CiteScore
11.10
自引率
4.60%
发文量
146
审稿时长
41 days
期刊介绍: The Journal of Lipid Research (JLR) publishes original articles and reviews in the broadly defined area of biological lipids. We encourage the submission of manuscripts relating to lipids, including those addressing problems in biochemistry, molecular biology, structural biology, cell biology, genetics, molecular medicine, clinical medicine and metabolism. Major criteria for acceptance of articles are new insights into mechanisms of lipid function and metabolism and/or genes regulating lipid metabolism along with sound primary experimental data. Interpretation of the data is the authors’ responsibility, and speculation should be labeled as such. Manuscripts that provide new ways of purifying, identifying and quantifying lipids are invited for the Methods section of the Journal. JLR encourages contributions from investigators in all countries, but articles must be submitted in clear and concise English.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信