ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation
ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation
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DOI：
10.1016/j.cmet.2005.01.002
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发表时间：
2005-02-01
期刊：
影响因子：
29
通讯作者：
Edwards, PA
中科院分区：
文献类型：
--
作者：
Kennedy, MA;Barrera, GC;Edwards, PA
在这里，我们证明ABC转运体Abcg1通过控制组织脂质水平和细胞胆固醇向HIDL的外流，在脂质动态平衡中发挥关键作用。在小鼠体内靶向阻断Abcg1对血脂没有影响，但在给予高脂肪和高胆固醇饮食后，导致中性脂和磷脂在肝细胞和多组织内的巨噬细胞中大量积聚。相反，过表达人类Abcg1可以保护小鼠组织免受饮食脂肪诱导的脂肪堆积。最后，我们发现胆固醇外流到高密度脂蛋白需要Abcg1，而外流到apoA1需要ABCA1。这些研究确定Abcg1是一个关键基因，参与胆固醇外流到高密度脂蛋白和组织脂质稳态。
Here we demonstrate that the ABC transporter ABCG1 plays a critical role in lipid homeostasis by controlling both tissue lipid levels and the efflux of cellular cholesterol to HIDL. Targeted disruption of Abcg1 in mice has no effect on plasma lipids but results in massive accumulation of both neutral lipids and phospholipids in hepatocytes and in macrophages within multiple tissues following administration of a high-fat and -cholesterol diet. In contrast, overexpression of human ABCG1 protects murine tissues from dietary fat-induced lipid accumulation. Finally, we show that cholesterol efflux to HDL specifically requires ABCG1, whereas efflux to apoA1 requires ABCA1. These studies identify Abcg1 as a key gene involved in both cholesterol efflux to HDL and in tissue lipid homeostasis.