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Effect of gemfibrozil on apolipoprotein B secretion and diacylglycerol acyltransferase activity in human hepatoblastoma (HepG2) cells.
- Source :
-
Atherosclerosis [Atherosclerosis] 2002 Oct; Vol. 164 (2), pp. 221-8. - 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 micromol/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 micromol/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.
- Subjects :
- Acyltransferases drug effects
Diacylglycerol O-Acyltransferase
Hepatoblastoma
Humans
Liver Neoplasms
Microsomes drug effects
Microsomes metabolism
Sensitivity and Specificity
Tumor Cells, Cultured
Acyltransferases metabolism
Apolipoproteins B drug effects
Apolipoproteins B metabolism
Gemfibrozil pharmacology
Liver cytology
Triglycerides metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9150
- Volume :
- 164
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Atherosclerosis
- Publication Type :
- Academic Journal
- Accession number :
- 12204791
- Full Text :
- https://doi.org/10.1016/s0021-9150(02)00060-6