DAX-1 is an atypical nuclear receptor (NR) which functions primarily as a transcriptional corepressor of other NRs via heterodimerization. Peroxisome proliferator-activated receptor (
PPAR)
x3b3; is a ligand-dependent NR which performs a key function in adipogenesis. In this study, we evaluated a novel cross-talk mechanism between DAX-1 and PPAR
x3b3;. Transient transfection assays demonstrated that DAX-1 inhibits the transactivity of PPAR
x3b3; in a dose-dependent manner. DAX-1 directly competed with the PPAR
x3b3; coactivator (PGC)-1
for binding to PPAR
x3b3;. Endogenous levels of DAX-1 were significantly lower in differentiated 3T3-L1 adipocytes as compared to preadipocytes. Using a retroviral expression system, we demonstrated that DAX-1 overexpression downregulates the expression of PPAR
x3b3; target genes, resulting in an attenuation of adipogenesis in 3T3-L1 cells. Our results suggest that DAX-1 acts as a corepressor of PPAR
x3b3; and performs a potential function in the regulation of PPAR
x3b3;-mediated cellular differentiation.