Sakuranetin (5,4'-dihydroxy-7-methoxyflavone) belongs to the flavanone class of polyphenols predominantly known as phytoalexin in rice plant. In this study, we demonstrate that sakuranetin strongly induces differentiation of 3T3-L1 preadipocytes, as evidenced by increased triglyceride accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity. In addition, even in the absence of adipogenic hormonal stimuli, sakuranetin strongly induced adipogenesis and expression of genes that are critical for the adipocytes phenotype. Time-course analyses indicated that sakuranetin induces PPAR gamma 2 expression without prior induction of C/EBP beta, a transcriptional regulator of PPAR gamma 2 in adipogenesis. In 3T3-L1 preadipocytes, the transcriptional factors GATA-2 and GATA-3 are known to down-regulate adipogenesis by direct binding to the C/EBP beta protein and to the GATA-binding site on the PPAR gamma 2 promoter. We found that sakuranetin significantly reduced the expression of GATA-2. Moreover, we observed that sakuranetin stimulated glucose uptake in differentiated 3T3-L1 adipocytes. These results suggest that sakuranetin may contribute to maintain glucose homeostasis in animals. (c) 2008 Elsevier Inc. All rights reserved.