ABCA1 缺乏会导致小鼠组织特异性 SREBP2 通路失调。

IF 3.9 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2024-07-31 DOI:10.1016/j.bbalip.2024.159546

Yoshio Yamauchi , Sumiko Abe-Dohmae , Noriyuki Iwamoto , Ryuichiro Sato , Shinji Yokoyama

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引用次数: 0

摘要

ABCA1 在高密度脂蛋白（HDL）的形成过程中起着至关重要的作用，它的突变会导致丹吉尔病（TD），这是一种家族性 HDL 缺乏症。除了高密度脂蛋白的消失外，TD 患者还表现出胆固醇在外周组织中沉积，其机制尚不清楚，这可能会导致过早发生动脉粥样硬化。我们和其他人以前曾发现，ABCA1 缺乏会导致体外 SREBP2 通路过度激活。在这里，我们发现在 Abca1 基因敲除小鼠中，ABCA1 缺乏会以营养状况依赖的方式导致组织特异性的 SREBP2 活性失调，这可能是 TD 病理生理学的基础。

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ABCA1 deficiency causes tissue-specific dysregulation of the SREBP2 pathway in mice

ABCA1 plays an essential role in the formation of high-density lipoprotein (HDL), and its mutations cause Tangier disease (TD), a familial HDL deficiency. In addition to the disappearance of HDL, TD patients exhibit cholesterol deposition in peripheral tissues through a mechanism poorly understood, which may contribute to the development of premature atherosclerosis. We and others previously showed that ABCA1 deficiency causes hyperactivation of the SREBP2 pathway in vitro. Here, we show using Abca1 knockout mice that ABCA1 deficiency leads to tissue-specific dysregulation of SREBP2 activity in a nutritional status-dependent manner, which may underlie the pathophysiology of TD.

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来源期刊

Biochimica et biophysica acta. Molecular and cell biology of lipids 生物-生化与分子生物学

CiteScore

11.00

自引率

2.10%

发文量

109

审稿时长

53 days

期刊介绍： BBA Molecular and Cell Biology of Lipids publishes papers on original research dealing with novel aspects of molecular genetics related to the lipidome, the biosynthesis of lipids, the role of lipids in cells and whole organisms, the regulation of lipid metabolism and function, and lipidomics in all organisms. Manuscripts should significantly advance the understanding of the molecular mechanisms underlying biological processes in which lipids are involved. Papers detailing novel methodology must report significant biochemical, molecular, or functional insight in the area of lipids.