Sterol carrier protein 2 gene transfer changes lipid metabolism and enterohepatic sterol circulation in mice.
Sterol carrier protein 2 gene transfer changes lipid metabolism and enterohepatic sterol circulation in mice.
复制标题
甾醇载体蛋白2基因转移改变小鼠的脂质代谢和肠肝甾醇循环。
DOI:
10.1053/gast.2000.20198
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发表时间:
2000
期刊:
影响因子:
29.4
通讯作者:
Nervi,F
中科院分区:
文献类型:
--
作者:
Zanlungo,S;Amigo,L;Mendoza,H;Miquel,JF;Vío,C;Glick,JM;Rodríguez,A;Kozarsky,K;Quiñones,V;Rigotti,A;Nervi,F
Background & AimsSterol carrier protein 2 (SCP-2) enhances sterol cycling and facilitates cholesterol translocation between intracellular organelles and plasma membrane in cultured cells, including hepatocytes. We examined the role of SCP-2 in hepatic cholesterol and lipid trafficking through the sinusoidal and canalicular secretory pathways of the liver in vivo.MethodsRecombinant adenovirus–mediated SCP-2 gene transfer was used to obtain hepatic overexpression of SCP-2 in C57BL/6 mice.ResultsSCP-2 overexpression in the mouse liver resulted in an 8-fold increase of SCP-2 protein levels and determined various effects on lipid metabolism. It decreased high-density lipoprotein cholesterol and increased low-density lipoprotein (LDL) cholesterol concentrations. The expressions of hepatic LDL receptor, apolipoprotein (apo) A-I, apoB, and apoE were decreased. SCP-2 overexpression also increased hepatic cholesterol concentration, associated with decreased cholesterol neosynthesis. Increased biliary cholesterol and bile acid secretion, bile acid pool size, and intestinal cholesterol absorption were also observed.ConclusionsThese results indicate that modulation of SCP-2 expression in the liver determines important modifications on lipoprotein metabolism, hepatic cholesterol synthesis and storage, biliary lipid secretion, bile acid metabolism, and intestinal cholesterol absorption.