CRF system involvement in compulsive eating: new cues from pre-clinical rat and C. elegans models

Aims: Stress, together with dieting and environmental negative affects is a common trigger of eating disorders, especially binge eating (BE) disorder. The aim of this study was to investigate the regulation of the CRF/CRF-1R-system in a validated rat model of BE and to develop an innovative BE-model in C. elegans, as well as to observe the potential involvement seb-3 gene, similar to the mammalian CRF-1R, on BE behavior. Methods: Female rats were exposed to food restriction and stress. mRNA abundances and DNA methylation were quantified by qRT-PCR and pyrosequencing. N2 worms and two different seb-3 mutants were exposure to starvation and acute stress, then alterations in feeding activity were recorded. Results: CRF system is up regulated in the VTA of rats restricted and exposed to stress, and these changes appear to be due to a reduction in DNA methylation at gene promoters. The pharyngeal pumping rate was increased in N2 worms exposed to starvation and stress conditions when compared to animals just starved. Moreover, seb-3 gain-of-function-worms resulted to be more sensitive to the starvation and stress conditions wherever, seb-3 loss-of-function-worms seemed to be not responding. Conclusions: These data further support the role of CRF-system in compulsive-feeding behavior. Morever, our new proposed BE-model in C. elegans could improve the understanding of the role played by CRF as well as other brain circuits and by environmental triggers in affecting food intake. We believe that this model would give the opportunity to monitor genetic modifications in order to follow disease development easily across worms life-span.