Repression of excessive increase and enlargement of adipocytes that is closely 
associated with obesity is effective in the prevention and treatment of 
metabolic syndrome. Generally, apoptosis is induced in cells via a wide variety 
of intracellular or extracellular substances, and recently, it has been 
suggested that the FoxO subfamily is involved in the induction of apoptosis. We 
aimed to elucidate the mechanism of FoxO-mediated apoptosis-induction in the 
adipocytes under the reactive oxygen species (ROS) stimulus. The treatment of 
differentiated and undifferentiated 3T3-L1 cells with glucose oxidase (GOD), an 
enzyme that generates H(2)O(2), induced apoptosis and led to the accumulation of 
8-OHdG. Apoptosis analysis revealed that GOD treatment induced apoptosis in 
differentiated 3T3-L1 cells less efficiently than in undifferentiated 
preadipocytes. GOD remarkably increased the levels of Bad, Bax, and Bim-the 
genes that are actively involved in cell apoptosis. GOD treatment also increased 
the expression of FoxO3a mRNA and protein. The introduction of FoxO3a-siRNA into 
3T3-L1 cells suppressed the oxidative stress-induced expression of Bim mRNA, as 
well as the GOD-induced apoptosis. Furthermore, the expression of MnSOD, 
Cu/ZnSOD, and catalase, as well as of FoxO, increased significantly along with 
the progression of adipocyte differentiation. These results indicated that 
ROS-induced apoptosis in undifferentiated 3T3-L1 cells via the expression of 
FoxO3a, whereas FoxO expression suppressed the ROS-induced apoptosis in 
differentiated 3T3-L1 cells via the expression of ROS-scavenging enzymes.