Cadmium inhibits the differentiation of 3T3-L1 preadipocyte through the C/EBPα and PPARγ pathways.

Cadmium, a well-known toxic heavy metal, affects cellular physiology by disturbing cellular signaling pathways. We investigate the effect of cadmium on cellular differentiation using 3T3-L1 preadipocyte cell lines as an in vitro model. Here, it was shown that cadmium (3 μM) significantly decreased both glycerol-3-phosphate dehydrogenase (GPDH) activity and lipid accumulation of differentiating 3T3-L1 cells in a dose-dependent manner. In addition, inhibitory action of cadmium on differentiating 3T3-L1 cells was effective only at the initial stage of 3T3-L1 preadipocyte differentiation. Western blot analysis revealed that cadmium suppressed the expression of CCAAT/enhancer-binding protein alpha (C/EBPα) and peroxisome proliferator-activator receptor gamma (PPARγ) proteins, key transcriptional activators for adipogenesis, in a dose-dependent manner. These results suggest that the inhibitory effects of cadmium on 3T3-L1 preadipocyte differentiation, as indicated by a decrease in GPDH activity and lipid accumulation, a marker of adipogenesis, appeared to be mediated through the downregulated expression of C/EBPα and PPARγ proteins.