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

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Lipids

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.

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Abbreviations

ACAT:

aeyl CoA:cholesterol acyltransferase

apo B:

apolipoprotein B

apoB-Lp:

apoB-containing lipoprotein

CE:

cholesteryl esters

DGAT:

diacylglycerol acyltransferase

EMSA:

electrophoretic mobility shift assay

ER:

endoplasmic reticulum

HMGR:

3-hydroxy-3-methylglutaryl-CoA reductase

MG-132:

carbobenzoxy-l-leucyl-l-leucyl-l-leucinal

MTP:

microsomal triglyceride transfer protein

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

PMF:

polymethoxyflavone(s)

PPAR:

peroxisome proliferator-activated receptor

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Author information

Authors and Affiliations

  1. Citrus & Subtropical Products Laboratory, USDA, ARS, South Atlantic Area, 33881, Winter Haven, Florida

    John A. Manthey

  2. Division of Medical Technology, John A. Burns School of Medicine, University of Hawaii at Manoa, 96822, Honolulu, Hawaii

    Adele Casaschi & Andre G. Theriault

  3. Research and Development Division, KGK Synergize Inc., Ste. 1030, 255 Queens Ave., N6A 5R8, London, ON, Canada

    Elzbieta M. Kurowska

Authors
  1. Elzbieta M. Kurowska
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  2. John A. Manthey
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  3. Adele Casaschi
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  4. Andre G. Theriault
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Correspondence to Elzbieta M. Kurowska.

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Kurowska, E.M., Manthey, J.A., Casaschi, A. et al. Modulation of hepG2 cell net apolipoprotein B secretion by the citrus polymethoxyflavone, tangeretin. Lipids 39, 143–151 (2004). https://doi.org/10.1007/s11745-004-1212-8

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  • DOI: https://doi.org/10.1007/s11745-004-1212-8

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