禁食状态下MED1肝脏特异性敲除鼠呈现高脂血症

摘要

MED1 is a key transcription co-activator subunit of the Mediator complex that is essential for RNA polymerase 11-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 MED1AL'V mice fasted for 24, 48 and 72 hours. Histological changes in liver sections from MED1 AL'V mice after 72 hours of fasting were also examined using H&E staining. There was no fat accumulation in livers of MEDlALiv mice compared to MEDl? And PPARa"'" control mice after 72 hours of fasting. Compared with MEDl mice, plasma triglycerides in MEDlALiv 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 MEDl"7" and MEDl mice. However, very low density lipoprotein (VLDL) was significantly increased in MEDl^"1 mice after 24 hours of fasting. We conclude that, hyperlipidemia in MEDlALlv 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.%为研究MED1如何影响血浆脂质代谢,以MED1肝脏特异性敲除鼠(MED 1ΔLiv)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MED lΔLiv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MED1 fl/fl和PPARα-/-对照鼠相比,MED1△Liv鼠肝脏无脂肪沉积.禁食24、48,72 h,与MED1 fl/fl鼠相比,MED1△Liv鼠血浆甘油三酯显著升高.禁食48 h和72 h,与MED1fl/fl鼠相比,MED1△Liv鼠血浆胆固醇显著升高.此外,饲喂条件下,MED1△Liv和MED1fl/fl鼠血浆脂蛋白分布无明显差异.然而,禁食24 h,MED1ΔLiv鼠中富含甘油三酯的极低密度脂蛋白高度积聚,表明MED1△Liv鼠呈现的高脂血症是由于极低密度脂蛋白的积聚引起,提示转录辅激活子MED1在富舍甘油三酯的脂蛋白代谢中起关键调控作用.