Structural requirements of flavonoids for the adipogenesis of 3T3-L1 cells

To search for a new class of antidiabetic compounds, effects of 44 Flavonoids on the adipogenesis of 3T3-L1 cells were examined. Among them, 3,4',7-trimethylkaempferol, tetramethylkaempferol, and pentamethylquercetin concentration-dependently enhanced the accumulation of triglyceride, a marker of adipogenesis. With regard to structural requirements of Flavonoids for the activity, it was fond that: (1) most Flavonoids having hydroxy groups lacked the effect; (2) Flavonols with methoxy groups showed stronger effects particularly those with a methoxy group at the 3-position; and (3) a methoxy group of Flavonols at the B ring was also important. 3,4',7-Trimethylkaempferol, tetramethylkaempferol, and pentamethylquercetin significantly increased the amount of Adiponectin released into the medium and the uptake of 2-deoxyglucose into the cells. Furthermore, tetramethylkaempferol and pentamethylquercetin also increased mRNA levels of Adiponectin, glucose transporter 4 (GLUT4), and fatty acid-binding protein (aP2). Both compounds also increased the mRNA levels of Peroxisome Proliferator-activated Receptor (PPAR)γ2 and CCAAT/enhancer-binding protein (C/EBP)α, β, and/or δ, although, different from troglitazone, they did not activate PPARγ directly in a nuclear receptor cofactor assay.