| First Author | Wang J | Year | 2016 |
| Journal | J Lipid Res | Volume | 57 |
| Issue | 9 | Pages | 1712-9 |
| PubMed ID | 27381048 | Mgi Jnum | J:235221 |
| Mgi Id | MGI:5795781 | Doi | 10.1194/jlr.M069682 |
| Citation | Wang J, et al. (2016) Intracellular cholesterol transport proteins enhance hydrolysis of HDL-CEs and facilitate elimination of cholesterol into bile. J Lipid Res 57(9):1712-9 |
| abstractText | While HDL-associated unesterified or free cholesterol (FC) is thought to be rapidly secreted into the bile, the fate of HDL-associated cholesteryl esters (HDL-CEs) that represent >80% of HDL-cholesterol, is only beginning to be understood. In the present study, we examined the hypothesis that intracellular cholesterol transport proteins [sterol carrier protein 2 (SCP2) and fatty acid binding protein-1 (FABP1)] not only facilitate CE hydrolase-mediated hydrolysis of HDL-CEs, but also enhance elimination of cholesterol into bile. Adenovirus-mediated overexpression of FABP1 or SCP2 in primary hepatocytes significantly increased hydrolysis of HDL-[(3)H]CE, reduced resecretion of HDL-CE-derived FC as nascent HDL, and increased its secretion as bile acids. Consistently, the flux of [(3)H]cholesterol from HDL-[(3)H]CE to biliary bile acids was increased by overexpression of SCP2 or FABP1 in vivo and reduced in SCP2(-/-) mice. Increased flux of HDL-[(3)H]CE to biliary FC was noted with FABP1 overexpression and in SCP2(-/-) mice that have increased FABP1 expression. Lack of a significant decrease in the flux of HDL-[(3)H]CE to biliary FC or bile acids in FABP1(-/-) mice indicates the likely compensation of its function by an as yet unidentified mechanism. Taken together, these studies demonstrate that FABP1 and SCP2 facilitate the preferential movement of HDL-CEs to bile for final elimination. |
