Bisphenol A induces Pomc gene expression through neuroinflammatory and PPARγ nuclear receptor-mediated mechanisms in POMC-expressing hypothalamic neuronal models

Endocrine disrupting chemicals, such as bisphenol A (BPA), have been linked to obesity. However, the direct effect of BPA on the hypothalamic pro-opiomelanocortin (POMC) neurons, which regulate energy homeostasis, remains unexplored. We define the effect of BPA on functionally characterized, POMC-expressing cell models, mHypoA-POMC/GFP-2 and mHypoE-43/5. Exposure to BPA significantly induced the mRNA levels of Pomc in both primary culture and the cell lines. Neuroinflammatory and steroid receptor mRNA levels were assessed to delineate the potential mechanisms, including inflammatory markers Nf kappa b, Il6 and I kappa ba, and steroid receptors Esr1, Esr2, Gpr30, Esrrg, and Pparg. Pre-treatment with anti-inflammatory compounds gonadotropin-releasing hormone, and PS1145, an I kappa B kinase inhibitor, abrogated the BPA-mediated Pomc induction. Furthermore, T0070907, a PPAR gamma antagonist, abolished Pomc induction, while the GPR30 antagonist G15 had no effect These findings indicate that BPA may have direct effects on POMC neurons in the hypothalamus, utilizing neuroinflammatory mechanisms and through PPAR gamma nuclear receptors.