禁食状态下MED1肝脏特异性敲除鼠呈现高脂血症

Hyperlipidemia in hepatic MED1 deficient mice in response to fasting

摘要:

为研究MED1如何影响血浆脂质代谢，以MED1肝脏特异性敲除鼠 (MED1ΔLiv) 为动物模型，禁食0、24、48、72 h，通过H&E染色切片观察了MED1ΔLiv鼠肝脏的形态学变化，运用甘油三酯和胆固醇酶试剂盒及FPLC方法分析了MED1ΔLiv和对照鼠 (MED1fl/fl) 血浆甘油三酯和胆固醇的水平以及脂蛋白的分布情况。研究结果显示，禁食72 h，与MED1fl/fl和PPARα?/?对照鼠相比，MED1ΔLiv鼠肝脏无脂肪沉积。禁食24、48、72 h，与MED1fl/fl鼠相比，MED1Δ

Abstract:

MED1 is a key transcription co-activator subunit of the Mediator complex that is essential for RNA polymerase II-dependent transcription. MED1 functions as a co-activator for PPARs and other nuclear receptors and transcription factors, and plays an important role in lipid metabolism. To examine how MED1 might affect plasma lipids, plasma triglyceride, cholesterol levels, and lipoprotein profiles, were measured in MED1ΔLiv mice fasted for 24, 48 and 72 hours. Histological changes in liver sections from MED1ΔLiv mice after 72 hours of fasting were also examined using H&E staining. There was no fat accumulation in livers of MED1ΔLiv mice compared to MED1fl/fl and PPARα?/? control mice after 72 hours of fasting. Compared with MED1fl/fl mice, plasma triglycerides in MED1ΔLiv mice were significantly increased after 24, 48 and 72 hours of fasting, and plasma cholesterol was significantly increased after 48 and 72 hours of fasting. Lipoprotein profiles were similar in fed MED1fl/fl and MED1ΔLiv mice. However, very low density lipoprotein (VLDL) was significantly increased in MED1ΔLiv mice after 24 hours of fasting. We conclude that, hyperlipidemia in MED1ΔLiv mice in response to fasting is due to the accumulation of VLDL, which suggests that MED1 plays a pivotal role in the regulation of plasma triglyceride and cholesterol levels.