| Autor: |
Jing Wang, Jinghua Bie, Shobha Ghosh |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
|
| Zdroj: |
Journal of Lipid Research, Vol 57, Iss 9, Pp 1712-1719 (2016) |
| Druh dokumentu: |
article |
| ISSN: |
0022-2275 |
| DOI: |
10.1194/jlr.M069682 |
| Popis: |
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-[3H]CE, reduced resecretion of HDL-CE-derived FC as nascent HDL, and increased its secretion as bile acids. Consistently, the flux of [3H]cholesterol from HDL-[3H]CE to biliary bile acids was increased by overexpression of SCP2 or FABP1 in vivo and reduced in SCP2−/− mice. Increased flux of HDL-[3H]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-[3H]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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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