Sterol carrier protein 2 gene transfer changes lipid metabolism and enterohepatic sterol circulation in mice

Background & Aims: Sterol 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. Methods : Recombinant adenovirus-mediated SCP-2 gene transfer was used to obtain he patic overexpression of SCP-2 in C57BL/6 mice. Results: SCP-2 overexpressio n 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-dens ity lipoprotein cholesterol and increased low-density lipoprotein (LDL) cho lesterol concentrations. The expressions of hepatic LDL receptor, apolipopr otein (apo) A-I, apoB, and apoE were decreased. SCP-2 overexpression also i ncreased hepatic cholesterol concentration, associated with decreased chole sterol neosynthesis. Increased biliary cholesterol and bile acid secretion, bile acid pool size, and intestinal cholesterol absorption were also obser ved. Conclusions: These results indicate that modulation of SCP-2 expressio n in the liver determines important modifications on lipoprotein metabolism , hepatic cholesterol synthesis and storage, biliary lipid secretion, bile acid metabolism and intestinal cholesterol absorption.