|Kurowska, Elzbieta - KGK SYNERGIZE INC, CANADA|
|Casaschi, Adele - UNIV OF HAWAII|
|Theriault, Andre - UNIV OF HAWAII|
Submitted to: Lipids
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 2, 2004
Publication Date: February 2, 2004
Citation: Kurowska, E.M., Manthey, J.A., Casaschi, A., Theriault, A.G. 2004. Modulation of hepg2 cell net apolipoprotein b secretion by the citrus polymethoxyflavone, tangeretin. Lipids. 39(2):143-151. Interpretive Summary: A chemical, called tangeretin, in orange peel byproducts has been shown to inhibit the production of a protein that is critical for the production of "bad" cholesterol in animals. This study dealt with the mechanism of this inhibitory effect. Tangeretin blocks the production of triglycerides (fats) by human liver cells. Other enzymes involved in triglyceride production and transport are also affected. The levels at which tangeretin is active towards liver cells is approximately the same levels detected in livers of hamsters fed a tangeretin-containing diet. These results suggest that tangeretin may possibly impart cardioprotective benefits in humans.
Technical Abstract: The purpose of the present study was to examine the role of tangeretin, a polymethoxylated flavone from citrus fruit, on the regulation of apolipoprotein B (apo B) and lipid metabolism in the human hepatoma cell-line, HepG2. The marked reduction in apo B secretion observed in cells incubated with 72.8 µM tangeretin was rapid, apo B-specific, and partly reversible. The reduction was observed also under lipid-rich condition and found to be insensitive to proteasomal degradation of nascent apo B. 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 ester, free cholesterol and triacylglycerol (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 diacylglycerol acyltransferase (DGAT) (up to -39.0 ± 3.0% vs. control) and microsomal triglyceride transfer protein (MTP) (up to -35.5 ±2.5% vs. control). Tangeretin was also found to activate peroxisome proliferators-activated receptor (PPAR), a transcription factor with a positive regulatory impact on fatty acid oxidation and TAG availability (up to 36% increase vs. control). The data suggest that tangeretin modulates apo B-containing lipoprotein metabolism through multiple mechanisms.