| Autor: |
Lin-Hua Zhang, Vaijinath S. Kamanna, Shobha H. Ganji, Xi-Ming Xiong, Moti L. Kashyap |
| Jazyk: |
angličtina |
| Rok vydání: |
2012 |
| Předmět: |
|
| Zdroj: |
Journal of Lipid Research, Vol 53, Iss 5, Pp 941-950 (2012) |
| Druh dokumentu: |
article |
| ISSN: |
0022-2275 |
| DOI: |
10.1194/jlr.M020917 |
| Popis: |
The lipidation of apoA-I in liver greatly influences HDL biogenesis and plasma HDL levels by stabilizing the secreted apoA-I. Niacin is the most effective lipid-regulating agent clinically available to raise HDL. This study was undertaken to identify regulatory mechanisms of niacin action in hepatic lipidation of apoA-I, a critical event involved in HDL biogenesis. In cultured human hepatocytes (HepG2), niacin increased: association of apoA-I with phospholipids and cholesterol by 46% and 23% respectively, formation of lipid-poor single apoA-I molecule-containing particles up to ∼ 2.4-fold, and pre β 1 and α migrating HDL particles. Niacin dose-dependently stimulated the cell efflux of phospholipid and cholesterol and increased transcription of ABCA1 gene and ABCA1 protein. Mutated DR4, a binding site for nuclear factor liver X receptor alpha (LXR α ) in the ABCA1 promoter, abolished niacin stimulatory effect. Further, knocking down LXR α or ABCA1 by RNA interference eliminated niacin-stimulated apoA-I lipidation. Niacin treatment did not change apoA-I gene expression. The present data indicate that niacin increases apoA-I lipidation by enhancing lipid efflux through a DR4-dependent transcription of ABCA1 gene in HepG2 cells. A stimulatory role of niacin in early hepatic formation of HDL particles suggests a new mechanism that contributes to niacin action to increase the stability of newly synthesized circulating HDL. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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