Modulation of HepG2 cell net apolipoprotein B secretion by the citrus polymethoxyflavone, tangeretin.
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 microM 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 microM 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.
Kurowska
Elzbieta M
EM
KGK Synergize Inc., Research and Development Division, London, Ontario, Canada N6A 5R8. kurowska@kgksynergize.com
Manthey
John A
JA
Casaschi
Adele
A
Theriault
Andre G
AG
D000217:Acyltransferases / Q000187:drug effects / Q000378:metabolism; D001055:Apolipoproteins B / Q000187:drug effects* / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D051048:Diacylglycerol O-Acyltransferase; D015536:Down-Regulation / Q000187:drug effects; D047309:Flavones / Q000494:pharmacology*; D006801:Humans; D047492:Peroxisome Proliferator-Activated Receptors / Q000187:drug effects / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis / Q000737:chemistry
D001055:Apolipoproteins B; D002352:Carrier Proteins; D047309:Flavones; D047492:Peroxisome Proliferator-Activated Receptors; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D000217:Acyltransferases; D051048:Diacylglycerol O-Acyltransferase; C059006:tangeretin