Sakuranetin induces adipogenesis of 3T3-L1 cells through enhanced expression of PPARgamma2.
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 PPARgamma2 expression without prior induction of C/EBPbeta, a transcriptional regulator of PPARgamma2 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/EBPbeta protein and to the GATA-binding site on the PPARgamma2 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.
National Agricultural Research Center for Western Region, 1-3-1 Senyu-cho, Zentsuji 765-8508, Kagawa, Japan.
Takeshi
T
Saito
Daigo
D
Abe
Keizo
K
Sekiya
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D005419:Flavonoids / Q000494:pharmacology*; D050989:GATA2 Transcription Factor / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism; D000094162:Phytoalexins
D005419:Flavonoids; D050989:GATA2 Transcription Factor; D005993:Glycerolphosphate Dehydrogenase; D047495:PPAR gamma; D014280:Triglycerides; C494712:Gata2 protein, mouse; C099724:sakuranetin; D000094162:Phytoalexins