Avicularin, a plant flavonoid, suppresses lipid accumulation through repression of C/EBPα-activated GLUT4-mediated glucose uptake in 3T3-L1 cells

J Agric Food Chem. 2013 May 29;61(21):5139-47. doi: 10.1021/jf401154c. Epub 2013 May 16.

Abstract

Avicularin (quercetin-3-O-α-L-arabinofuranoside) is a plant flavonoid and a quercetin glycoside. In this study, we found that avicularin suppressed the accumulation of intracellular lipids through repression of glucose transporter 4 (GLUT4)-mediated glucose uptake in mouse adipocytic 3T3-L1 cells. Avicularin was highly purified (purity of more than at least 99%) from Taxillus kaempferi (DC.) Danser (Loranthaceae) by high-performance liquid chromatography, and its structure was determined by nuclear magnetic resonance and mass spectrometry. Avicularin decreased the intracellular triglyceride level along with a reduction in the expression of adipogenic genes such as peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein (C/EBP) α, and aP2 (fatty acid-binding protein 4). In contrast, avicularin did not affect the expression of lipogenic and lipolytic genes. Interestingly, the expression of the GLUT4 gene was significantly suppressed in an avicularin-concentration-dependent manner. Moreover, the binding of C/EBPα to the promoter region of the GLUT4 gene was repressed by adding avicularin to the medium in 3T3-L1 cells, as demonstrated by the results of a chromatin immunoprecipitation assay. These results indicate that avicularin inhibited the accumulation of the intracellular lipids by decreasing C/EBPα-activated GLUT4-mediated glucose uptake in adipocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Animals
  • CCAAT-Enhancer-Binding Protein-alpha / genetics
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism*
  • Down-Regulation / drug effects
  • Flavonoids / pharmacology*
  • Glucose / metabolism*
  • Glucose Transporter Type 4 / genetics*
  • Glucose Transporter Type 4 / metabolism
  • Lipid Metabolism / drug effects*
  • Mice
  • Plant Extracts / pharmacology*
  • Transcriptional Activation / drug effects*

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • Flavonoids
  • Glucose Transporter Type 4
  • Plant Extracts
  • avicularin
  • Glucose