Modulation of hepG2 cell net apolipoprotein B secretion by the citrus polymethoxyflavone, tangeretin

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Abstract
The purpose of the present study was to examine the role of tangeretin, a polymethoxylated flavone from citrus fruits, on the regulation of apolipoprotein B (apoB) and lipid metabolism in the human hepatoma cell‐line HepG2. The marked reduction in apoB secretion observed in cells incubated with 72.8 μM tangeretin was rapid, apoB‐specific, and partly reversible. The reduction also was observed under lipid‐rich conditions and found to be insensitive to proteasomal degradation of nascent apoB. We followed our study by examining lipid synthesis and mass. A 24‐h exposure of cells to 72.8 μM tangeretin decreased intracellular synthesis of cholesteryl esters, free cholesterol, and TAG by 82, 45, and 64%, respectively; tangeretin also reduced the mass of cellular TAG by 37%. The tangeretin‐induced suppression of TAG synthesis and mass were associated with decreased activities of DAG acyltransferase (up to‐39.0±3.0% vs. control) and microsomal triglyceride transfer protein (up to−35.5±2.5% vs. control). Tangeretin was also found to activate the peroxisome proliferator‐activated receptor, a transcription factor with a positive regulatory impact on FA oxidation and TAG availability (up to 36% increase vs. control). The data suggest that tangeretin modulates apoB‐containing lipoprotein metabolism through multiple mechanisms.