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, Annabelle Rodríguez, Hydeyuki Hyogo, David Cohen, Attilio Rigotti, and Flavio Nervi

Gastroenterología, Pontificia Universidad Católica de Chile, Santiago Cas114_D

Corresponding Author: 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 over express 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 FA and cholesterol synthesis to < 62% of control mice. Hepatic triglyceride contents were decreased; while cholesterol and phospholipids concentrations were elevated in Ad.rSCP2 mice. In plasma of Ad.rSCP2 animals, LDL cholesterol levels were increased and HDL cholesterol concentrations were decreased. Hepatic VLDL triglyceride production fell in Ad.rSCP2 mice to 39% of control values. Biliary cholesterol, phospholipids and bile acids outputs were increased in Ad.rSCP2 mice. Biliary PC hydrophobic index increased by 100% in Ad.rSCP2. These studies indicate that SCP-2 over expression 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.

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