Cafeteria diet differentially alters the expression of feeding-related genes through DNA methylation mechanisms in individual hypothalamic nuclei

- Cafeteria diet increased the expression of orexigenic neuropeptides in PVN and VMN.
- The orexigenic signal of PVN and VMN was mildly counteracted by the ARC.
- Cafeteria diet altered the expression of different hormone receptors in VMN and ARC.
- Cafeteria diet changed the mRNA levels of neurosteroidogenic enzymes in PVN and VMN.
- These changes were associated with modifications in promoter methylation states.

We evaluated the effect of cafeteria diet (CAF) on the mRNA levels and DNA methylation state of feeding-related neuropeptides, and neurosteroidogenic enzymes in discrete hypothalamic nuclei. Besides, the expression of steroid hormone receptors was analyzed. Female rats fed with CAF from weaning increased their energy intake, body weight, and fat depots, but did not develop metabolic syndrome. The increase in energy intake was related to an orexigenic signal of paraventricular (PVN) and ventromedial (VMN) nuclei, given principally by upregulation of AgRP and NPY. This was mildly counteracted by the arcuate nucleus, with decreased AgRP expression and increased POMC and kisspeptin expression. CAF altered the transcription of neurosteroidogenic enzymes in PVN and VMN, and epigenetic mechanisms associated with differential promoter methylation were involved. The changes observed in the hypothalamic nuclei studied could add information about their differential role in food intake control and how their action is disrupted in obesity.