Regulation of Pigment Epithelium-Derived Factor (PEDF), an Insulin Resistance-Inducing Adipocytokine, in 3T3-L1 Adipocytes

Pigment epithelium-derived factor (PEDF), secreted by adipocytes, was recently demonstrated to reduce insulin sensitivity and to possibly cause insulin resistance in obesity. In the present study, we investigated the regulation of adipocyte-expressing PEDF to clarify the underlying link between obesity and PEDF expression. We examined PEDF expression in 3T3-L1 adipocytes at both the transcriptional and the protein level using RT-PCR and western blot. First, we examined PEDF expression during 3T3-L1 adipocyte differentiation. PEDF expression peaked in 3T3-L1 fibroblasts and was lowest at 2 days after initiating the induction of differentiation into adipocytes (day 2). Then, PEDF expressions gradually rose until day 10, in parallel with adipocyte differentiation. Exposure of 3T3-L1 adipocytes to a PPARa or PPAR. activator reduced PEDF expression, suggesting these suppressions of PEDF expression to be involved in the mechanism by which PPAR agonists reduce insulin resistance. When 3T3-L1 adipocytes were treated with 0.5 mu M H2O2, PEDF levels were markedly reduced, indicating PEDF expression to be inhibited by oxidative stress. We demonstrated PEDF expression to increase in parallel with adipocyte differentiation and to be negatively regulated by oxidative stress and PPAR agonists.