中科院再生生物學重點實驗室青年學者進階培訓計劃之青年論壇

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

主講人：徐瑩瑩 博士

時 間：5月26日 10:30（星期四）

主持人：師靖軒 博士

地 點：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.