The link with oxytocin appears particularly interesting in the functional context: hypothalamic Fto mRNA-positive neurons display an increased level of colocalization with an immediate-early gene product, c-Fos, at meal termination compared to initiation [10]. The distribution of c-Fos immunoreactive Fto SCH66336 in the paraventricular and supraoptic nuclei at the end of a meal closely resembles the topography of neuronal populations synthesizing a satiety mediator, oxytocin [10], [17] and [18].
The current project was aimed at exploring the presumed functional relationship between Fto and oxytocin. We used double immunohistochemistry to examine the percentage of oxytocin neurons containing nuclear profiles positive for the Fto protein in the male and female murine brain. We examined the level of colocalization in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, the two main sites encompassing oxytocin neuronal populations. We then overexpressed Fto in a mouse hypothalamic cell line and employed real-time PCR to study whether overexpression of this transcription co-activator affects oxytocin mRNA levels. Relative expression of other feeding-related candidate interactor genes: POMC, NPY and Agouti-related protein (AgRP), was also determined. Finally, we evaluated whether addition of oxytocin to the culture medium serves as negative feedback for the expression of Fto in hypothalamic cells.