Effect of genistein and daidzein on the proliferation and differentiation of human preadipocyte cell line.

Isoflavones are known to have several biological activities, including a hypolipidemic effect. However, the mechanism of the lipid lowering effect of genistein remains to be elucidated. There is conflicting evidence on the effect of genistein for the deposition of adipocyte tissues. We examined the effect of the isoflavones on the growth and differentiation of human preadipocyte cells, AML-I. Growth arrest accompanied by the appearance of characteristics of apoptosis was observed by genistein or daidzein treatment under the adipogenic stimulation. The expressions of apoptosis-related proteins, Bad, Akt, and p-Akt, were modulated in the genistein-treated cells by Western blot analysis. On the other hand, exposure of AML-I to the isoflavones increased accumulation of cytoplasmic lipid droplets. Actually, the cytoplasmic expressions of fatty acid synthase (FAS) and peroxisome proliferator-activated receptor (PPAR)-gamma were increased in the genistein-treated cells. Glycosylated forms of the isoflavones genistein and puerarin did not have such activities. These results suggested that only aglycon forms of isoflavones induced not only apoptosis but also lipogenesis in the preadipocyte cell line AML-I. The possible mechanism of these phenomena has been discussed in the text.