Avicularin, a Plant Flavonoid, Suppresses Lipid Accumulation through Repression of C/EBPα-Activated GLUT4-Mediated Glucose Uptake in 3T3-L1 Cells

Avicularin (quercetin-3-O-alpha-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 gamma, CCAAT/enhancer-binding protein (C/EBP) alpha, 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/EBP alpha 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/EBP alpha-activated GLUT4-mediated glucose uptake in adipocytes.