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

Journal of Lipid Research

Hideyuki Hyogo¹  Silvana Zanlungo¹  Flavio Nervi¹  David E. Cohen²  Juan Francisco Miquel²  Jane M. Glick³  Attilio Rigotti³  Ludwig Amigo³ 

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

关键词: hepatic lipid metabolism;    bile;    SCP-2;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown