title: Structural requirements of flavonoids for the adipogenesis of 3T3-L1 cells.
abstract: 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.
authors.affiliation: Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Matsuda
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kogami
authors.forename: Seikou
authors.initials: S
authors.lastname: Nakamura
authors.forename: Tomomi
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Ueno
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshikawa
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D050556:Fatty Acid-Binding Proteins; D005419:Flavonoids; D051275:Glucose Transporter Type 4; D047495:PPAR gamma; D051743:CCAAT-Enhancer-Binding Protein-delta; D003847:Deoxyglucose