Sterol carrier protein 2 gene transfer changes lipid metabolism and enterohepatic sterol circulation in mice

Silvana Zanlungo, Ludwig Amigo, Hegaly Mendoza, Juan Francisco Miquel, Carlos Vi, Jane M. Glick, Annabelle Rodri, Karen Kozarsky, Verónica Quiones, Attilio Rigotti, Flavio Nervi

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

Background & Aims: 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.

Original languageEnglish
Pages (from-to)1708-1719
Number of pages12
JournalGastroenterology
Volume119
Issue number6
DOIs
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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