Hien Hoang Thi Minh, Ha Nguyen Cam, Thom Le Thi, Hong Dang Diem
Institute of Biotechnology (IBT), Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.
Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.
Biotechnol Lett. 2017 Aug;39(8):1101-1107. doi: 10.1007/s10529-017-2345-y. Epub 2017 May 10.
To examine the effect of squalene on liver X receptors (LXRs) that regulate target genes associated with reverse cholesterol transport and thus control whole-body cholesterol homeostasis.
To examine the effect of squalene on liver X receptors (LXRs) that regulate target genes associated with reverse cholesterol transport and thus control whole-body cholesterol homeostasis. Squalene significantly stimulated the transactivation of liver X receptor modulator LXRα and LXRβ. The mRNA expression of LXRs and their target genes, including ABCA1, ABCG1 and ApoE, was significantly induced in macrophages stimulated with squalene, resulting in removal of cholesterol from the cells. Notably, squalene did not induce higher hepatic triacylglycerol levels nor did it alter expression of sterol regulatory element-binding protein 1c (SREBP-1c) and FAS in hepatocyte cells, primarily because of its upregulation of Insig-2a, which delays nuclear translocation of SREBP-1c, a key hepatic lipogenic transcription factor.
Squalene has hypocholesterolemic effect through the activation of LXRα and β without inducing hepatic lipogenesis.
研究角鲨烯对肝脏X受体（LXRs）的影响，LXRs可调节与胆固醇逆向转运相关的靶基因，从而控制全身胆固醇稳态。
研究角鲨烯对肝脏X受体（LXRs）的影响，LXRs可调节与胆固醇逆向转运相关的靶基因，从而控制全身胆固醇稳态。角鲨烯显著刺激肝脏X受体调节剂LXRα和LXRβ的反式激活作用。在用角鲨烯刺激巨噬细胞后，LXRs及其靶基因（包括ABCA1、ABCG1和ApoE）的mRNA表达显著上调，导致细胞内胆固醇清除。值得注意的是, 角鲨烯不会导致肝脏三酰甘油水平升高, 也不会改变肝细胞中固醇调节元件结合蛋白1c（SREBP-1c）和脂肪酸合酶（FAS）的表达,这主要是因为它上调了Insig-2a, 从而延迟了关键肝脏脂肪生成转录因子SREBP-1c的核转位。
角鲨烯通过激活LXRα和β发挥降胆固醇作用，且不会诱导肝脏脂肪生成。
