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CGI-58或脂肪甘油三酯脂肪酶的缺失对巨噬细胞功能和动脉粥样硬化的影响不同。

Deletion of CGI-58 or adipose triglyceride lipase differently affects macrophage function and atherosclerosis.

作者信息

Goeritzer Madeleine, Schlager Stefanie, Radovic Branislav, Madreiter Corina T, Rainer Silvia, Thomas Gwynneth, Lord Caleb C, Sacks Jessica, Brown Amanda L, Vujic Nemanja, Obrowsky Sascha, Sachdev Vinay, Kolb Dagmar, Chandak Prakash G, Graier Wolfgang F, Sattler Wolfgang, Brown J Mark, Kratky Dagmar

机构信息

Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.

Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC.

出版信息

J Lipid Res. 2014 Dec;55(12):2562-75. doi: 10.1194/jlr.M052613. Epub 2014 Oct 14.

DOI:10.1194/jlr.M052613
PMID:25316883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4242449/
Abstract

Cellular TG stores are efficiently hydrolyzed by adipose TG lipase (ATGL). Its coactivator comparative gene identification-58 (CGI-58) strongly increases ATGL-mediated TG catabolism in cell culture experiments. To investigate the consequences of CGI-58 deficiency in murine macrophages, we generated mice with a targeted deletion of CGI-58 in myeloid cells (macCGI-58(-/-) mice). CGI-58(-/-) macrophages accumulate intracellular TG-rich lipid droplets and have decreased phagocytic capacity, comparable to ATGL(-/-) macrophages. In contrast to ATGL(-/-) macrophages, however, CGI-58(-/-) macrophages have intact mitochondria and show no indications of mitochondrial apoptosis and endoplasmic reticulum stress, suggesting that TG accumulation per se lacks a significant role in processes leading to mitochondrial dysfunction. Another notable difference is the fact that CGI-58(-/-) macrophages adopt an M1-like phenotype in vitro. Finally, we investigated atherosclerosis susceptibility in macCGI-58/ApoE-double KO (DKO) animals. In response to high-fat/high-cholesterol diet feeding, DKO animals showed comparable plaque formation as observed in ApoE(-/-) mice. In agreement, antisense oligonucleotide-mediated knockdown of CGI-58 in LDL receptor(-/-) mice did not alter atherosclerosis burden in the aortic root. These results suggest that macrophage function and atherosclerosis susceptibility differ fundamentally in these two animal models with disturbed TG catabolism, showing a more severe phenotype by ATGL deficiency.

摘要

细胞内的甘油三酯（TG）储存可被脂肪甘油三酯脂肪酶（ATGL）有效水解。其辅激活因子比较基因识别-58（CGI-58）在细胞培养实验中能显著增强ATGL介导的TG分解代谢。为了研究CGI-58缺陷在小鼠巨噬细胞中的后果，我们构建了髓系细胞中CGI-58靶向缺失的小鼠（macCGI-58(-/-)小鼠）。CGI-58(-/-)巨噬细胞积累富含TG的细胞内脂滴，吞噬能力下降，这与ATGL(-/-)巨噬细胞类似。然而，与ATGL(-/-)巨噬细胞不同的是，CGI-58(-/-)巨噬细胞的线粒体完好，未显示出线粒体凋亡和内质网应激的迹象，这表明TG积累本身在导致线粒体功能障碍的过程中没有显著作用。另一个显著差异是，CGI-58(-/-)巨噬细胞在体外呈现出类似M1的表型。最后，我们研究了macCGI-58/ApoE双敲除（DKO）动物的动脉粥样硬化易感性。在高脂/高胆固醇饮食喂养下，DKO动物的斑块形成情况与ApoE(-/-)小鼠相当。同样，在低密度脂蛋白受体(-/-)小鼠中，反义寡核苷酸介导的CGI-58敲低并未改变主动脉根部的动脉粥样硬化负担。这些结果表明，在这两种TG分解代谢紊乱的动物模型中，巨噬细胞功能和动脉粥样硬化易感性存在根本差异，ATGL缺陷表现出更严重的表型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df5/4242449/eab7303628cf/2562fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df5/4242449/1d2a7581affd/2562fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df5/4242449/fefbb415ffb1/2562fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df5/4242449/e05f3b1a9c1d/2562fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df5/4242449/89ca9fe60d90/2562fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df5/4242449/3e40b2d2e95b/2562fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df5/4242449/62ef38f63b1c/2562fig6a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df5/4242449/eab7303628cf/2562fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df5/4242449/1d2a7581affd/2562fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df5/4242449/fefbb415ffb1/2562fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df5/4242449/e05f3b1a9c1d/2562fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df5/4242449/89ca9fe60d90/2562fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df5/4242449/3e40b2d2e95b/2562fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df5/4242449/62ef38f63b1c/2562fig6a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2df5/4242449/eab7303628cf/2562fig7.jpg

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3
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Proc Natl Acad Sci U S A. 2022 Mar 22;119(12):e2114739119. doi: 10.1073/pnas.2114739119. Epub 2022 Mar 18.
4
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