Antiadipogenic Effects and Mechanisms of Combinations of Genistein, Epigallocatechin-3-Gallate, and/or Resveratrol in Preadipocytes

摘要

Natural bioactive compounds are considered an excellent alternative strategy for developing effective, safe, and cost-effective antiobesity agents. The aim of this study was to investigate if combinations of soy bean genistein (G), green tea epigallocatechin-3-gallate (E), and/or grape resveratrol (R) at low dosages synergistically inhibit preadipocyte differentiation both in 3T3-L1 cells and human primary preadipocytes (HPAs). Our results show that combinations of G, E, and/or R additively inhibited preadipocyte differentiation (39-56% of control) both in 3T3-L1 cells at 30 mu M and HPAs at 15 mu M, while the individual compounds have no antiadipogenic effect at the selected concentrations. We also observed similar patterns that combinations of G, E, and/or R additively reduced protein expressions of peroxisome proliferator-activated receptor gamma (PPAR-gamma) and CCAAT binding proteins alpha (C/EBP-alpha), the two key preadipocyte differentiation regulators, both in differentiated 3T3-L1 cells and HPAs. Moreover, combined G, E, and/or R attenuated protein expressions of fatty acid binding protein 4 and perilipin, two PPAR-gamma/C/EBP-alpha downstream molecules in fat drop development in a very similar pattern, in inhibiting differentiation in preadipocytes. This combined antiadipogenic effect of G+E+ R is additive, not synergistic according to our results and the Median-Effect Principle. In addition, we found that a lower concentration (15 mu M) of G, E, and/or R is required in HPAs than the concentration (30 mu M) needed in 3T3-L1 cells, to exert the combined antiadipogenic effect. These data suggest that combinations of G, E, and/or R intake or soy bean, green tea, and/or grape simultaneous consumption may prevent obesity in human being.