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Overexpresssion of Sterol Carrier Protein-2 in Mice Leads to Increased Hepatic Cholesterol and Enterohepatic Circulation of Bile Acids

S. Zanlungo, L. Amigo, H. Mendoza, J. Glick, A. Rodríguez, K. Kozarsky, A. Rigotti, J. F. Miquel, F. Nervi.:

Presentado a: Congreso anual de la American Gastroenterological Association. 20 al 26 de Mayo, 2000. San Diego, California, Estados Unidos.

 

Sterol carrier protein-2 (SCP2) is likely to play an important role in hepatic cellular cholesterol metabolism and trafficking. We have previously described some of the phenotypic characteristics of mice overexpressing the SCP2 gene by adenovirus-mediated gene transfer (Gastroenterology 1999; 116:A1293). Hepatic SCP2 overexpression increased biliary lipid secretion and altered plasma lipoprotein cholesterol (increase in LDL/IDL cholesterol associated with decreased HDL cholesterol).

Aim: To further characterize the physiological role of SCP2 on hepatic cholesterol and bile acid metabolism in the SCP2 overexpressing mouse model.

Methods and Results: Recombinant rat SCP2 adenovirus (Ad.rSCP2) was used to infect C57BL/6 mice. Controls included either uninfected mice or mice infected with recombinant adenovirus that lacks a cDNA transgene (Ad.E1D). All the experiments were performed 7 days post-adenoviral infection. Hepatic SCP2 overexpression increased hepatic total cholesterol content by 70%, whereas it decreased hepatic cholesterol synthesis by 60%. The SCP2 overexpressing animals showed a significant increase in the bile acid pool size (1.14-fold, p < 0.025), whereas no changes were observed in fecal bile acid excretion or bile acid pool composition.

Conclusions: Hepatic SCP2 overexpression increased hepatic cholesterol content and bile acid pool size. These findings strongly suggests that SCP2 indeed plays an important role in regulating hepatic cholesterol and bile acid metabolism in vivo.

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