| dc.description.abstract |
The present study examined the role of xanthohumol (XN), a plant chalcone, on apolipoprotein B (apoB) and triglyceride (TG) synthesis and secretion, using HepG2 cells as the model system. The data indicated that XN decreased apoB secretion in a dose-dependent manner under both basal and lipid-rich conditions (as much as 43% at 15 μmol/L). This decrease was associated with increased cellular apoB degradation. To determine the mechanism underlying this effect, we examined triglyceride availability, a major factor in the regulation of apoB secretion. XN inhibited the synthesis of TG in the microsomal membrane and the transfer of this newly synthesized TG to the microsomal lumen (decreases of 26 and 64%, respectively, under lipid-rich conditions), indicating that TG availability is a determining factor in the regulation of apoB secretion under the experimental conditions. The inhibition of TG synthesis was caused by a reduction in diacylglycerol acyltransferase (DGAT) activity, which corresponded to a decrease in DGAT-1 mRNA expression, but not DGAT-2 expression. Microsomal triglyceride transfer protein (MTP) may also control the rate of TG transfer from the microsomal membrane to the active lumenal pool. XN decreased MTP activity in a dose-dependent manner (as much as 30%). Whether the reduction in TG accumulation in the microsomal lumen is predominantly due to DGAT and/or MTP activity remains unknown. In summary, the data suggest that xanthohumol is a potent inhibitor of apoB secretion. |
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