Sterol carrier protein 2 gene transfer changes lipid metabolism and enterohepatic sterol circulation in mice.
OBJECTIVE
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 hepatic overexpression of SCP-2 in C57BL/6 mice.


RESULTS
SCP-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.


CONCLUSIONS
These 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.
Zanlungo
S
S
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Santiago, Chile.
Amigo
L
L
Mendoza
H
H
Miquel
J F
JF
Vío
C
C
Glick
J M
JM
Rodríguez
A
A
Kozarsky
K
K
Quiñones
V
V
Rigotti
A
A
Nervi
F
F
D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D018014:Gene Transfer Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010940:Plant Proteins; D013261:Sterols / Q000097:blood*
D001053:Apolipoproteins; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D008077:Lipoproteins, LDL; D010940:Plant Proteins; D013261:Sterols; C072087:sterol carrier proteins; D002784:Cholesterol