Transcriptional regulation of the endocannabinoid system in a rat model of binge-eating behavior reveals a selective modulation of the hypothalamic fatty acid amide hydrolase gene

Objective: Binge-eating episodes are recurrent and are defining features of several eating disorders. Thus binge-eating episodes might influence eating disorder development of which exact underlying mechanisms are still largely unknown. Methods: Here we focused on the transcriptional regulation of the endocannabinoid system, a potent regulator of feeding behavior, in relevant rat brain regions, using a rat model in which a history of intermittent food restriction and a frustration stress induce binge-like palatable food consumption. Results: We observed a selective down-regulation of fatty acid amide hydrolase (faah) gene expression in the hypothalamus of rats showing the binge-eating behavior with a consistent reduction in histone 3 acetylation at lysine 4 of the gene promoter. No relevant changes were detected for any other endocannabinoid system components in any brain regions under study, as well as for the other epigenetic mechanisms investigated (DNA methylation and histone 3 lysine 27 methylation) at the faah gene promoter. Discussion: Our findings suggest that faah transcriptional regulation is a potential biomarker of binge-eating episodes, with a relevant role in the homeostatic regulation of food intake.