Arsenic inhibits the adipogenic differentiation of mesenchymal stem cells by down-regulating peroxisome proliferator-activated receptor gamma and CCAAT enhancer-binding proteins.

Arsenic remains a top environmental concern in the United States as well as worldwide because of its global existence and serious health impacts. Apoptotic effect of arsenic in human mesenchymal stem cells (hMSCs) has been identified in our previous study; the effects of arsenic on hMSCs remain largely unknown. Here, we report that arsenic inhibits the adipogenic differentiation of human mesenchymal stem cells (hMSCs). Arsenic reduced the formation of lipid droplets and the expression of adipogenesis-related proteins, such as CCAAT enhancer binding protein-(C/EBPs), peroxisome proliferator-activated receptor-gamma (PPAR-γ), and adipocyte fatty acid-binding protein aP2 (aP2). Arsenic mediates this process by sustaining PPAR-γ activity. In addition, inhibition of PPAR-γ activity with T0070907 and up-regulation with its agonist troglitazone, showed the direct association of PPAR-γ and arsenic-mediated inhibition of differentiating hMSCs. Taken together, these results indicate that arsenic inhibits adipogenic differentiation through PPAR-γ pathway and suggest a novel inhibitory effect of arsenic on adipogenic differentiation in hMSCs. Crown