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LXRα 对于载脂蛋白 E 缺陷小鼠最大程度的胆固醇逆转运和动脉粥样硬化保护是必需的。

LXRα is uniquely required for maximal reverse cholesterol transport and atheroprotection in ApoE-deficient mice.

机构信息

Howard Hughes Medical Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.

出版信息

J Lipid Res. 2012 Jun;53(6):1126-33. doi: 10.1194/jlr.M022061. Epub 2012 Mar 26.

DOI:10.1194/jlr.M022061
PMID:22454476
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3351819/
Abstract

The liver X receptor (LXR) signaling pathway is an important modulator of atherosclerosis, but the relative importance of the two LXRs in atheroprotection is incompletely understood. We show here that LXRα, the dominant LXR isotype expressed in liver, plays a particularly important role in whole-body sterol homeostasis. In the context of the ApoE(-/-) background, deletion of LXRα, but not LXRβ, led to prominent increases in atherosclerosis and peripheral cholesterol accumulation. However, combined loss of LXRα and LXRβ on the ApoE(-/-) background led to an even more severe cholesterol accumulation phenotype compared to LXRα(-/-)ApoE(-/-) mice, indicating that LXRβ does contribute to reverse cholesterol transport (RCT) but that this contribution is quantitatively less important than that of LXRα. Unexpectedly, macrophages did not appear to underlie the differential phenotype of LXRα(-/-)ApoE(-/-) and LXRβ(-/-)ApoE(-/-) mice, as in vitro assays revealed no difference in the efficiency of cholesterol efflux from isolated macrophages. By contrast, in vivo assays of RCT using exogenously labeled macrophages revealed a marked defect in fecal sterol efflux in LXRα(-/-)ApoE(-/-) mice. Mechanistically, this defect was linked to a specific requirement for LXRα(-/-) in the expression of hepatic LXR target genes involved in sterol transport and metabolism. These studies reveal a previously unrecognized requirement for hepatic LXRα for optimal reverse cholesterol transport in mice.

摘要

肝 X 受体 (LXR) 信号通路是动脉粥样硬化的重要调节剂，但两种 LXR 在动脉粥样硬化保护中的相对重要性尚不完全清楚。我们在这里表明，肝脏中表达的主要 LXR 亚型 LXRα 在全身固醇稳态中起着特别重要的作用。在 ApoE(-/-)背景下，LXRα 的缺失，但不是 LXRβ 的缺失，导致动脉粥样硬化和外周胆固醇积累显著增加。然而，与 LXRα(-/-)ApoE(-/-)小鼠相比，LXRα 和 LXRβ 的联合缺失导致更严重的胆固醇积累表型，表明 LXRβ确实有助于胆固醇逆转运 (RCT)，但这种贡献的数量不如 LXRα 重要。出乎意料的是，巨噬细胞似乎不是 LXRα(-/-)ApoE(-/-)和 LXRβ(-/-)ApoE(-/-)小鼠差异表型的基础，因为体外测定显示从分离的巨噬细胞中胆固醇流出的效率没有差异。相比之下，使用外源性标记的巨噬细胞进行体内 RCT 测定显示，LXRα(-/-)ApoE(-/-)小鼠粪便中固醇的排出明显缺陷。从机制上讲，这种缺陷与肝脏 LXR 靶基因参与固醇转运和代谢的表达中对 LXRα(-/-)的特定需求有关。这些研究揭示了肝脏 LXRα 在小鼠最佳胆固醇逆转运中以前未被认识到的需求。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/98fd994182fc/1126fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/82d1678ee429/1126fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/ef26e8961877/1126fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/ad58ea3d3b51/1126fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/1bcac7b426b2/1126fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/02b688114360/1126fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/a01f7ffb8bb4/1126fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/0f028b6caf9c/1126fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/98fd994182fc/1126fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/82d1678ee429/1126fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/ef26e8961877/1126fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/ad58ea3d3b51/1126fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/1bcac7b426b2/1126fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/02b688114360/1126fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/a01f7ffb8bb4/1126fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/0f028b6caf9c/1126fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3104/3351819/98fd994182fc/1126fig8.jpg

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2
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J Lipid Res. 2011 Mar;52(3):531-9. doi: 10.1194/jlr.M010686. Epub 2010 Dec 27.
3
Non-redundant roles for LXRalpha and LXRbeta in atherosclerosis susceptibility in low density lipoprotein receptor knockout mice.
Nutrients. 2023 Jan 1;15(1):224. doi: 10.3390/nu15010224.
4
Nuclear receptors, cholesterol homeostasis and the immune system.核受体、胆固醇稳态和免疫系统。
J Steroid Biochem Mol Biol. 2019 Jul;191:105364. doi: 10.1016/j.jsbmb.2019.04.013. Epub 2019 Apr 16.
5
Common and Differential Transcriptional Actions of Nuclear Receptors Liver X Receptors α and β in Macrophages.核受体肝 X 受体 α 和 β 在巨噬细胞中的常见和差异转录作用。
Mol Cell Biol. 2019 Feb 15;39(5). doi: 10.1128/MCB.00376-18. Print 2019 Mar 1.
6
(-)-Epigallocatechin-3-Gallate Ameliorates Atherosclerosis and Modulates Hepatic Lipid Metabolic Gene Expression in Apolipoprotein E Knockout Mice: Involvement of TTC39B.（-）-表没食子儿茶素-3-没食子酸酯改善载脂蛋白E基因敲除小鼠的动脉粥样硬化并调节肝脏脂质代谢基因表达：TTC39B的作用
Front Pharmacol. 2018 Mar 9;9:195. doi: 10.3389/fphar.2018.00195. eCollection 2018.
7
Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP.通过 RNF145 依赖的 SCAP 泛素化抑制胆固醇生物合成。
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8
The challenges and promise of targeting the Liver X Receptors for treatment of inflammatory disease.针对肝 X 受体治疗炎症性疾病的挑战与前景。
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9
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6
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9
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10
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