Rayalam Srujana, Della-Fera Mary Anne, Yang Jeong-Yeh, Park Hea Jin, Ambati Suresh, Baile Clifton A
Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602-2771, USA.
J Nutr. 2007 Dec;137(12):2668-73. doi: 10.1093/jn/137.12.2668.
Genistein (G) and resveratrol (R) individually inhibit adipogenesis in 3T3-L1 adipocytes and induce apoptosis in cancer cells. We investigated whether the combination of G and R resulted in enhanced effects on adipogenesis, lipolysis, and apoptosis in 3T3-L1 cells. Preadipocytes and mature adipocytes were treated with G and R individually at 50 and 100 micromol/L (G100; R100) and in combination. Both in preadipocytes and mature adipocytes, G and R individually decreased cell viability dose-dependently, but G100 + R100 further decreased viability by 59 +/- 0.97% (P < 0.001) and 69.7 +/- 1.2% (P < 0.001) after 48 h compared with G100 and R100, respectively. G100 + R100 induced apoptosis 242 +/- 8.7% (P < 0.001) more than the control after 48 h, whereas G100 and R100 individually increased apoptosis only 46 +/- 9.2 and 46 +/- 7.9%, respectively. G and R did not modulate mitogen-activated protein kinase expression by themselves, but G100 + R100 increased Jun-N-terminal kinase phosphorylation by 38.8 +/- 4.4% (P < 0.001) and decreased extracellular signal-regulating kinase phosphorylation by 48 +/- 3.4% (P < 0.001). Individually, G and R at 25 micromol/L (G25; R25) decreased lipid accumulation by 30 +/- 1.7% and 20.07 +/- 4.27%, respectively (P < 0.001). However, G25 + R25 decreased lipid accumulation by 77.9 +/- 3.4% (P < 0.001). Lipolysis assay revealed that neither G25 nor R25 induced lipolysis, whereas G25 + R25 significantly increased lipolysis by 25.5 +/- 4.6%. The adipocyte-specific proteins PPARgamma and CCAAT/enhancer binding protein-alpha were downregulated after treatment with G + R, but no effect was observed with individual compounds. These results indicate that G and R in combination produce enhanced effects on inhibiting adipogenesis, inducing apoptosis, and promoting lipolysis in 3T3-L1 adipocytes. Thus, the combination of G and R is more potent in exerting antiobesity effects than the individual compounds.
染料木黄酮（G）和白藜芦醇（R）分别抑制3T3-L1脂肪细胞的脂肪生成，并诱导癌细胞凋亡。我们研究了G和R联合使用是否会增强对3T3-L1细胞脂肪生成、脂肪分解和凋亡的影响。将前脂肪细胞和成熟脂肪细胞分别用50和100微摩尔/升的G和R（G100；R100）单独处理以及联合处理。在前脂肪细胞和成熟脂肪细胞中，G和R单独处理均剂量依赖性地降低细胞活力，但与G100和R100相比，48小时后G100 + R100进一步使细胞活力分别降低了59±0.97%（P < 0.001）和69.7±1.2%（P < 0.001）。48小时后，G100 + R100诱导的凋亡比对照组多242±8.7%（P < 0.001），而G100和R100单独处理分别仅使凋亡增加46±9.2%和46±7.9%。G和R自身并未调节丝裂原活化蛋白激酶的表达，但G100 + R100使Jun-N末端激酶磷酸化增加了38.8±4.4%（P < 0.001），并使细胞外信号调节激酶磷酸化降低了48±3.4%（P < 0.001）。单独使用时，25微摩尔/升的G（G25）和R（R25）分别使脂质积累减少30±1.7%和20.07±4.27%（P < 0.001）。然而，G25 + R25使脂质积累减少了77.9±3.4%（P < 0.001）。脂肪分解测定显示，G25和R25均未诱导脂肪分解，而G25 + R25显著使脂肪分解增加了25.5±4.6%。用G + R处理后，脂肪细胞特异性蛋白PPARγ和CCAAT/增强子结合蛋白α下调，但单独使用各化合物时未观察到这种效果。这些结果表明，G和R联合使用对抑制3T3-L1脂肪细胞的脂肪生成、诱导凋亡和促进脂肪分解具有增强作用。因此，G和R联合使用在发挥抗肥胖作用方面比单独使用各化合物更有效。
