Hepatic overexpression of sterol carrier protein-2 inhibits VLDL production and reciprocally enhances biliary lipid secretion.
We examined in vivo a role for sterol carrier protein-2 (SCP-2) in the regulation of lipid secretion across the hepatic sinusoidal and canalicular membranes. Recombinant adenovirus Ad.rSCP2 was used to overexpress SCP-2 in livers of mice. We determined plasma, hepatic, and biliary lipid concentrations; hepatic fatty acid (FA) and cholesterol synthesis; hepatic and biliary phosphatidylcholine (PC) molecular species; and VLDL triglyceride production. In Ad.rSCP2 mice, there was marked inhibition of hepatic fatty acids and cholesterol synthesis to <62% of control mice. Hepatic triglyceride contents were decreased, while cholesterol and phospholipids concentrations were elevated in Ad.rSCP2 mice. Hepatic VLDL triglyceride production fell in Ad.rSCP2 mice to 39% of control values. As expected, biliary cholesterol, phospholipids, bile acids outputs, and biliary PC hydrophobic index were significantly increased in Ad.rSCP2 mice. These studies indicate that SCP-2 overexpression in the liver markedly inhibits lipid synthesis as well as VLDL production, and alters hepatic lipid contents. In contrast, SCP-2 increased biliary lipid secretion and the proportion of hydrophobic PC molecular species in bile. These effects suggest a key regulatory role for SCP-2 in hepatic lipid metabolism and the existence of a reciprocal relationship between the fluxes of lipids across the sinusoidal and canalicular membranes.
Amigo
Ludwig
L
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Santiago, Chile.
Zanlungo
Silvana
S
Miquel
Juan Francisco
JF
Glick
Jane M
JM
Hyogo
Hideyuki
H
Cohen
David E
DE
Rigotti
Attilio
A
Nervi
Flavio
F
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D003902:Detergents / Q000378:metabolism; D050356:Lipid Metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*
D002352:Carrier Proteins; D003902:Detergents; D008079:Lipoproteins, VLDL; D010713:Phosphatidylcholines; D014280:Triglycerides; C072087:sterol carrier proteins; C030106:very low density lipoprotein triglyceride; D002784:Cholesterol