Pyriproxyfen promotes lipid accumulation in 3T3-L1 adipocytes by enhancement of TR4 activity

Insect hormones and their synthetic analogs have been suggested to modulate gene expression in mammals. Thus, we investigated to determine the role of pyriproxyfen, a juvenile hormone (JH) analog, in the transcriptional activity of TR4, which functions as a key modulator of energy homeostasis. Here, we demonstrate that 100 mu M pyriproxyfen enhances TR4 transcriptional activity with increase of expression of TR4 target genes such as FATP1 and PEPCK in 3T3-L1 adipocytes. Furthermore, pyriproxyfen treatment resulted in increase of lipid accumulation during adipocyte differentiation of 3T3-L1 cells. In reporter gene assays, pyriproxyfen promotes TR4 transactivation of the reporter genes linked to different target gene promoters. Knockdown of TR4 in 3T3-L1 cells abolished promoting effect of 100 mu M pyriproxyfen on lipid accumulation and expression of lipogenic genes, suggesting that pyriproxyfen may regulate adipogenesis of 3T3-L1 cells via modulation of TR4 transcriptional activity. Together, our results suggest that pyriproxyfen, a JH analog, may modulate lipid homeostasis in adipocytes via regulation of TR4 activity.