Bisphenol A Alters the Levels of miRNAs That Directly and/or Indirectly Target Neuropeptide Y in Murine Hypothalamic Neurons.

The hypothalamus is a vital regulator of energy homeostasis. Orexigenic neuropeptide Y (NPY) neurons within the hypothalamus can stimulate feeding and suppress energy expenditure, and dysregulation of these neurons may contribute to obesity. We previously reported that bisphenol A (BPA), an endocrine disruptor with obesogenic properties, alters transcription in hypothalamic neurons by inducing oxidative stress. We hypothesized that hypothalamic microRNAs (miRNAs), a class of small non-coding RNAs, could directly regulate gene expression by binding the 3' untranslated region (UTR). Five predicted -targeting miRNA candidates were uncovered through TargetScan and were detected in -expressing hypothalamic neuronal cell models and hypothalamic neuronal primary cultures. BPA dysregulated the expression of a number of these hypothalamic miRNAs. We examined the effects of putative -targeting miRNAs using miRNA mimics, and we found that miR-143-3p, miR-140-5p, miR-29b-1-5p, and let-7b-3p altered expression in the murine hypothalamic cell lines. Importantly, miR-143-3p targets the mouse 3' UTR, as detected using a luciferase construct containing the potential 3' UTR binding sites. Overall, this study established the first hypothalamic miRNA that directly targets the 3' UTR of mouse , emphasizing the involvement of miRNAs in the NPY system and providing an alternative target for control of NPY levels.