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Hypomorphic ASGR1 modulates lipid homeostasis via INSIG1-mediated SREBP signaling suppression

发表日期:2022-05-26来源:放大 缩小

中科院再生生物学重点实验室青年学者进阶培训计划之青年论坛 

Hypomorphic ASGR1 modulates lipid homeostasis via INSIG1-mediated SREBP signaling suppression 

主讲人:徐莹莹 博士 

时 间:5月26日 10:30(星期四) 

主持人:师靖轩 博士 

地 点:E228

Achievement introduction: 

A population genetic study identified that the asialoglycoprotein receptor 1 (ASGR1) mutation carriers had substantially lower non–HDL-c levels and reduced risks of cardiovascular diseases. However, the mechanism behind this phenomenon remained unclear. Here, we established Asgr1-knockout mice that represented a plasma lipid profile with significantly lower non–HDL-c and triglyceride caused by decreased secretion and increased uptake of VLDL/LDL. These 2 phenotypes were linked with fewer nuclear SREBPs (nSREBP). Furthermore, we demonstrated that increased insulin-induced gene 1 (INSIG1) is a critical factor responsible for ASGR1 deficiency–associated lipid profile changes and nSREBP suppression. This finding of an ASGR1/INSIG1/SREBP axis regulating lipid hemostasis may provide multiple potential targets for lipid-lowering drug development.  

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