title: Avicularin, a plant flavonoid, suppresses lipid accumulation through repression of C/EBPα-activated GLUT4-mediated glucose uptake in 3T3-L1 cells.
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.
authors: Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. fujimori@gly.oups.ac.jp
authors: Ko
authors: K
authors: Fujimori
authors: Makio
authors: M
authors: Shibano
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics* / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D005419:Flavonoids; D051275:Glucose Transporter Type 4; D010936:Plant Extracts; C041388:avicularin; D005947:Glucose