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Effect of gemfibrozil on apolipoprotein B secretion and diacylglycerol acyltransferase activity in human hepatoblastoma (HepG2) cells
- Source :
-
Atherosclerosis (00219150) . Oct2002, Vol. 164 Issue 2, p221. 8p. - Publication Year :
- 2002
-
Abstract
- The mechanism of action of a widely used drug gemfibrozil to reduce triglycerides (TG) and apolipoprotein B (apo B) is incompletely understood. Using human hepatoblastoma (HepG2) cells, we examined the effect of gemfibrozil on apo B secretion and TG synthesis catalyzed by diacylglycerol acyltransferase (DGAT), primary processes associated with the secretion of LDL. Gemfibrozil significantly decreased apo B secretion by HepG2 cells. It decreased oleate-induced stimulation of apo B secretion, suggesting that gemfibrozil-mediated inhibition of apo B secretion may be dependent on the synthesis of TG catalyzed by DGAT. Pre-incubation of HepG2 cells with gemfibrozil (200–400 μmol/l for 48 h) significantly inhibited microsomal DGAT activity. When added directly to the DGAT assay system containing control microsomes, gemfibrozil significantly inhibited the activity of DGAT by 14–25%. Gemfibrozil (200–400 μmol/l) inhibited TG synthesis by 47–50% as measured by the incorporation of 3H-oleic acid into TG. The data indicate that gemfibrozil inhibits DGAT activity resulting in decreased synthesis of TG and its availability for apo B lipidation rendering it susceptible to intracellular apo B degradation leading to the decreased secretion. These in-vitro data suggest a novel additional mechanism by which gemfibrozil lowers plasma TG and atherogenic apo B lipoproteins in dyslipidemic patients. [Copyright &y& Elsevier]
- Subjects :
- *APOLIPOPROTEINS
*TRIGLYCERIDES
Subjects
Details
- Language :
- English
- ISSN :
- 00219150
- Volume :
- 164
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Atherosclerosis (00219150)
- Publication Type :
- Academic Journal
- Accession number :
- 7789724
- Full Text :
- https://doi.org/10.1016/S0021-9150(02)00060-6