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Journal of Lipid Research, Vol. 44, 399-407, February 2003
Copyright © 2003 by Lipid Research, Inc.

Hepatic overexpression of sterol carrier protein-2 inhibits VLDL production and reciprocally enhances biliary lipid secretion

Ludwig Amigo^*, Silvana Zanlungo^*, Juan Francisco Miquel^*, Jane M. Glick, Hideyuki Hyogo, David E. Cohen, Attilio Rigotti^* and Flavio Nervi^1,*

^* Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Santiago, Chile
Institute for Human Gene Therapy, University of Pennsylvania, Philadelphia, PA
Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY

¹ To whom correspondence should be addressed. e-mail: fnervi{at}med.puc.cl

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.

Abbreviations: apo, apolipoprotein; bw, body weight; FA-acyl-CoA, long chain fatty acids-acyl CoA; SCP-2, sterol carrier protein-2; SCP-X, sterol carrier protein-X

Supplementary key words hepatic lipid metabolism • bile • SCP-2

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