Niacin accelerates intracellular apoB degradation by inhibiting triacylglycerol synthesis in human hepatoblastoma (HepG2) cells

Citation
Fy. Jin et al., Niacin accelerates intracellular apoB degradation by inhibiting triacylglycerol synthesis in human hepatoblastoma (HepG2) cells, ART THROM V, 19(4), 1999, pp. 1051-1059
Citations number
36
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
ISSN journal
10795642 → ACNP
Volume
19
Issue
4
Year of publication
1999
Pages
1051 - 1059
Database
ISI
SICI code
1079-5642(199904)19:4<1051:NAIADB>2.0.ZU;2-Z
Abstract
The mechanism by which the potent drug niacin decreases apoB-containing ath erogenic lipoproteins and prevents coronary disease is unclear. Utilizing h uman hepatoblastoma (HepG2) cells as an in vitro model, we have examined th e effect of niacin on intracellular degradation of apoB and the regulatory mechanisms involved in apoB processing. Niacin significantly increased apoB degradation in a dose- and time-dependent manner. Treatment of HepG2 cells with calpain inhibitor I [N-acetyl-leucyl-leucyl-norleucinal (ALLN), an in hibitor of certain protease-mediated apoB degradation], did not alter niaci n-induced apoB degradation. Niacin decreased inhibition of oleate-mediated apoB degradation. Niacin dose-dependently inhibited the synthesis of both f atty acids and triacylglycerol (TG) by 20% to 40% as determined by the inco rporation of C-14-acetate and H-3-glycerol into fatty acids and TC, respect ively. Incubation of HepG2 cells with niacin significantly inhibited (by 12 % to 15%) fatty acid esterification to produce TG as assessed by the incorp oration of H-3-oleic acid into TG. C-14-acetate incorporation into choleste rol and phospholipids was unchanged. The activity of microsomal triglycerid e transfer protein (MTP), a carrier protein for lipids, was not altered by pretreatment of cells with niacin. ApoB mRNA expression and I-125-LDL prote in uptake were also unchanged. These data indicate that niacin accelerates hepatic intracellular post-translational degradation of apoB by selectively reducing triglyceride synthesis (through inhibiting both fatty acid synthe sis and fatty acid esterification to produce TG) without affecting ALLN-inh ibitable protease- or MTP-mediated intracellular apoB processing, resulting in decreased apoB secretion and hence lower circulating levels of the athe rogenic lipoproteins.