A long-wave UVA filter avobenzone induces obesogenic phenotypes in normal human epidermal keratinocytes and mesenchymal stem cells

Avobenzone is the most commonly used ultraviolet (UV) A filter ingredient in sunscreen. To investigate the biological activity of avobenzone in normal human epidermal keratinocytes (NHEKs), the genome-scale transcriptional profile of NHEKs was performed. In this microarray study, we found 273 up-regulated and 274 down-regulated differentially expressed genes (DEGs) in NHEKs treated with avobenzone (10 mu M). Gene Ontology (GO) enrichment analysis showed that avobenzone significantly increased the DEGs associated with lipid metabolism in NHEKs. In addition, avobenzone increased the gene transcription of peroxisome proliferator-activated receptor gamma (PPAR gamma) and fatty acid binding protein 4 in NHEKs, implicating that avobenzone may be one of the metabolic disrupting obesogens. To confirm the obesogenic potential, we examined the effect of avobenzone on adipogenesis in human bone marrow mesenchymal stem cells (hBM-MSCs). Avobenzone (EC50, 14.1 mu M) significantly promoted adipogenesis in hBM-MSCs as its positive control obesogenic chemicals. Avobenzone (10 mu M) significantly up-regulated mRNA levels of PPAR gamma during adipogenesis in hBM-MSCs. However, avobenzone did not directly bind to PPAR gamma and the avobenzone-induced adipogenesis-promoting activity was not affected by PPAR gamma antagonists T0070907 and GW9662. Therefore, avobenzone promoted adipogenesis in hBM-MSCs through a PPAR gamma-independent mechanism. This study suggests that avobenzone functions as a metabolic disrupting obesogen.