Epigenetic regulation of hypothalamic neuropeptides gene expression in diet induced obesity resistant rats

A variety of factors plays a role in obesity (i.e. behavior, environment, and genetics) and epigenetic regulation of gene expression has emerged as a potential contributor in the susceptibility and development of obesity. To investigate the individual sensitivity to weight gain/resistance, we here studied genes transcription regulation of hypothalamic neuropeptides involved in the control of energy balance in rats developing (diet-induced obese, DIO) or not obesity (diet resistant, DR), when fed with a high fat diet (HFD). Rats have been followed up to 21 weeks of HFD exposure. After 5 weeks HFD exposure, the obese phenotype has been developed and we observed a selective down-regulation of the orexygenic neuropeptide Y (NPY) and peroxisome proliferatoractivated receptor gamma (PPAR-γ) genes and no changes for the agouti-related protein (AgRP), as well as for all the anorexigenic genes under study. After long-term HFD exposure (21 weeks), NPY and PPARγ, as well as most of the genes under study, resulted not to be different between DIO and DR whereas a lower expression of the anorexigenic pro-opio-melanocortin (POMC) gene in DIO rats when compared to DR. We also observed that changes in NPY and POMC mRNA were inversely correlated with gene promoters DNA methylation. Our findings suggest that selective alterations in hypothalamic peptide genes regulation could contribute to the development of overweight in rats and that environmental factor, as in this animal model, might be partially responsible of these changes via epigenetic mechanism.