Genistein, a major soy isoflavone, has been reported to exhibit antiadipogenic and proapoptotic potential in vivo and in vitro. It is also a phytoestrogen which has high affinity to estrogen receptor Î². In this study, we determined the effect of genistein on adipogenesis and estrogen receptor (ER) Î± and Î² expression during differentiation in primary human preadipocytes. Genistein inhibited lipid accumulation in a dose-dependent manner at concentrations of 6.25 Î¼M and higher, with 50 Î¼M genistein inhibiting lipid accumulation almost completely. Low concentrations of genistein (3.25 Î¼M) increased cell viability and higher concentrations (25 and 50 Î¼M) decreased it by 16.48Â±1.35% (P<.0001) and 50.68Â±1.34% (P<.0001). Oil Red O staining was used to confirm the effects on lipid accumulation. The inhibition of lipid accumulation was associated with inhibition of glycerol-3-phosphate dehydrogenase activity and down-regulation of expression of adipocyte-specific genes, including peroxisome proliferator-activated receptor Î³, CCAAT/enhancer binding protein Î±, glycerol-3-phosphate dehydrogenase, adipocyte fatty acid binding protein, fatty acid synthase, sterol regulatory element-binding protein 1, perilipin, leptin, lipoprotein lipase and hormone-sensitive lipase. These effects of genistein during the differentiation period were associated with down-regulation of ERÎ± and ERÎ² expression. This study adds to the elucidation of the molecular pathways involved in the inhibition of adipogenesis by phytoestrogens. Â© 2009 Elsevier Inc. All rights reserved.
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